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- Title
- Astrogliosis and its correlates with injury and disease: GFAP immunocytochemistry in the rat brain.
- Creator
- Taft, Janna Renee., Florida Atlantic University, Perry, Gary W.
- Abstract/Description
-
Astrogliosis may contribute to the pathogenesis of CNS dysfunction as in Alzheimer's Disease or Sudden Infant Death Syndrome (SIDS). Investigating astrocytic expression in the brain may provide valuable insights into and/or models of CNS disease or injury. This study was designed to test astrocyte expression and distribution in the mature rat and immature rat and cat brain utilizing different fixatives (aldehyde or ethanol), immunocytochemistry (glial fibrillary acidic protein, GFAP, or...
Show moreAstrogliosis may contribute to the pathogenesis of CNS dysfunction as in Alzheimer's Disease or Sudden Infant Death Syndrome (SIDS). Investigating astrocytic expression in the brain may provide valuable insights into and/or models of CNS disease or injury. This study was designed to test astrocyte expression and distribution in the mature rat and immature rat and cat brain utilizing different fixatives (aldehyde or ethanol), immunocytochemistry (glial fibrillary acidic protein, GFAP, or vimentin), and lesion conditions in the cortex, cerebellum, and brainstem. Findings include a paucity of GFAP positive astrocytes in most regions of the normal rat brainstem, evidence of astrogliosis in lesions, and the most intense, reactive astrocytes in the 7 day post-lesion condition. The results imply that the rat (brainstem) may make a suitable animal model for investigating the role of hypoxia and astrogliosis in neural trauma such as postulated in SIDS.
Show less - Date Issued
- 1999
- PURL
- http://purl.flvc.org/fcla/dt/15744
- Subject Headings
- Astrocytes, Neuroglia, Nervous system, Nervous system--Degeneration
- Format
- Document (PDF)
- Title
- Dscam1 Regulates Synapse Formation and Function in the Giant Fiber System of Drosophila.
- Creator
- Spencer, Casey L., Murphey, Rodney, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
- Abstract/Description
-
Proper formation of synapses in the developing nervous system is critical to the expected function and behavior of an adult organism. Neurons must project neurites, in the form of axons or dendrites, to target areas to complete synaptic circuits. The biochemical tool that cells use to interact with the external environment and direct the guidance of developing neurites are guidance receptors. One such guidance receptor that is extensively studied to uncover its roles in developmental...
Show moreProper formation of synapses in the developing nervous system is critical to the expected function and behavior of an adult organism. Neurons must project neurites, in the form of axons or dendrites, to target areas to complete synaptic circuits. The biochemical tool that cells use to interact with the external environment and direct the guidance of developing neurites are guidance receptors. One such guidance receptor that is extensively studied to uncover its roles in developmental disorders and disease is DSCAM (Down-Syndrome Cell Adhesion Molecule). To better understand the role of DSCAM in humans, a fly homolog Dscam1 was extensively characterized in the giant fiber system (GFS) of Drosophila to further explore its roles in axon guidance, synapse formation, and synapse function. The UAS-Gal4 system was used to alter the protein levels of Dscam1 within the giant fiber interneurons (GFs). A UAS-RNAi construct against Dscam1 was used to knockdown translation of all possible isoforms within the GFs. A UAS-Dscam1(TM2) construct was used to overexpress a single isoform of Dscam1 that is specifically trafficked to the axons. Confocal microscopy was used to determine the morphological changes associated with dysregulated Dscam1 levels. Visualization via fluorescent markers was accomplished of both pre- and post-synaptic cells, the GFs and tergotrochanteral motorneurons (TTMns), respectively, and synapse interface was determined as colocalization of the two cells. Additionally, the functional components of the GF-TTMn synapse, both gap-junctions, and presynaptic chemical active zones were tagged via fluorescent antibodies and quantified.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014364
- Subject Headings
- Drosophila, Cell Adhesion Molecules, Nervous System, Synapses
- Format
- Document (PDF)
- Title
- Calpain Cleavage of GAD65 is pathological and impairs gaba neurotransmission.
- Creator
- Buddhala, Chandana, Suarez, Marjorie, Alexandrescu, Anamaria, Pissaris, Adam, Modi, Jigar P., Wei, Jianning, Prentice, Howard, Wu, Jang-Yen, Graduate College
- Date Issued
- 2011-04-08
- PURL
- http://purl.flvc.org/fcla/dt/3164511
- Subject Headings
- Nervous System Diseases, GABA --physiology, Gamma-aminoboterzuur
- Format
- Document (PDF)
- Title
- Frazzled’s Role in Synapse Formation at a Drosophila Giant Synapse.
- Creator
- Lopez, Juan, Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
In Drosophila melanogaster, the GFS is synaptically coupled to the Tergotrochanteral motoneurons; these neurons form a signaling pathway from the brain to the jump muscles (Thomas and Wyman, 1983). Part of this signaling is done through gap junctions, and placement of these gap junctions was partially shown to be regulated by the binding of Netrin, a class of guidance molecule (Orr et al., 2014). In the present study we investigate the role of Netrin's receptor Frazzled in the placement of...
Show moreIn Drosophila melanogaster, the GFS is synaptically coupled to the Tergotrochanteral motoneurons; these neurons form a signaling pathway from the brain to the jump muscles (Thomas and Wyman, 1983). Part of this signaling is done through gap junctions, and placement of these gap junctions was partially shown to be regulated by the binding of Netrin, a class of guidance molecule (Orr et al., 2014). In the present study we investigate the role of Netrin's receptor Frazzled in the placement of gap junctions in Drosophila at: 1) Presynaptic neurons (Giant Fibers [GF]), 2) Postsynaptic neurons (Tergotrochanteral motoneurons [TTMn]), and 3) Presynaptic + Postsynaptic neurons simultaneously. Effects of Frazzled were tested using Frazzled RNAi and a combination of electrophysiological recordings and imaging of the GF-TTMn synapse. The results from this study show that presynaptic and postsynaptic knockdown of Frazzled delayed muscular responses and altered the anatomy of both the GF's and TTMn's.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013085
- Subject Headings
- Drosophila melanogaster--Nervous system., Gap Junctions., Synapses., Netrin Receptors.
- Format
- Document (PDF)
- Title
- KLEINE-LEVIN SYNDROME: INVESTIGATING THE IMMUNO-REACTIVITY OF PATIENT SERA TOWARDS VARIOUS BRAIN AREAS.
- Creator
- Hamper, Michael C., Wei, Jianning, Hartmann, James, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Kleine-Levin Syndrome (KLS) is an extremely rare neurological disorder characterized by episodes of uncontrollable hypersomnia and various cognitive and behavioral abnormalities. There is neither a definitive etiology nor definite treatment modalities. Immunological studies for this condition are extremely limited, and this present study aims to investigate a potential autoimmune mechanism that underlies KLS. To achieve this, western blot and dot-blot assays analyzed the immunoreactivity of...
Show moreKleine-Levin Syndrome (KLS) is an extremely rare neurological disorder characterized by episodes of uncontrollable hypersomnia and various cognitive and behavioral abnormalities. There is neither a definitive etiology nor definite treatment modalities. Immunological studies for this condition are extremely limited, and this present study aims to investigate a potential autoimmune mechanism that underlies KLS. To achieve this, western blot and dot-blot assays analyzed the immunoreactivity of patients and control sera towards various brain tissue areas. Western blot did not show immunoreactivity with IgG-depleted brain tissue lysate. However, dot-blot assays revealed a significantly greater level of immunoreactivity with KLS patient sera towards the dorsolateral prefrontal cortex, hypothalamus, and parieto-temporal areas compared to KLS-negative sera. These areas have previously been shown to be hypo-perfused in KLS patients. Future studies are necessary to identify the specific antibodies that may be autoreactive in KLS patients.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014359
- Subject Headings
- Kleine-Levin Syndrome, Autoantibodies, Hypersomnia, Nervous System Diseases
- Format
- Document (PDF)
- Title
- GABAERGIC NEUROTRANSMISSION AND POTENTIAL RESCUE METHODS FROM CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHIES IN C. ELEGANS.
- Creator
- Gonzalez-Lerma, Paola X., Dawson-Scully, Kenneth, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
- Abstract/Description
-
Cancer is a leading cause of death in the U.S and across the world, with estimates indicating 17 million new cancer cases in 2018, 9.5 million of which resulted in death. Statistics show that in the past 20 years cancer death rates have decreased 27% due to emerging therapies. The use of chemotherapies to kill fast-growing cells in the body has become one of the most common cancer treatments in the world today. Chemotherapy-Induced Peripheral Neuropathies (CIPNs) are the most common side...
Show moreCancer is a leading cause of death in the U.S and across the world, with estimates indicating 17 million new cancer cases in 2018, 9.5 million of which resulted in death. Statistics show that in the past 20 years cancer death rates have decreased 27% due to emerging therapies. The use of chemotherapies to kill fast-growing cells in the body has become one of the most common cancer treatments in the world today. Chemotherapy-Induced Peripheral Neuropathies (CIPNs) are the most common side effects caused by chemotherapeutic agents. CIPNs have a prevalence of up to 85% in cancer patients undergoing chemotherapy. CIPNs triggered by chemotherapeutic drug use severely damage nerves branching from either the brain or spinal cord, initiating the development of acute and/or chronic symptoms. Platinum-based and taxane-based chemotherapeutics are among the most potent and versatile drugs available for combating cancer. The two of these drugs, carboplatin and docetaxel, are known to cause peripheral neuropathies and central neurotoxicity and were the focus of this project.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014450
- Subject Headings
- Peripheral Nervous System Diseases, Chemotherapy, Caenorhabditis elegans, Cancer
- Format
- Document (PDF)
- Title
- The role of BimEL in the pathogenesis of Huntington's disease.
- Creator
- Leon, Rebecca, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Huntington's Disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the Huntingtin gene IT15. In this study we demonstrated that Bcl-2 interacting mediator of cell death Extra Long (BimEL) protein expression was significantly increased in cells expressing mutant Huntingtin (mHtt). Moreover, striatal BimEL expression remained high in an R6/2 HD mouse model throughout the disease progression. Utilizing novel BimEL phospho-mutants we...
Show moreHuntington's Disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the Huntingtin gene IT15. In this study we demonstrated that Bcl-2 interacting mediator of cell death Extra Long (BimEL) protein expression was significantly increased in cells expressing mutant Huntingtin (mHtt). Moreover, striatal BimEL expression remained high in an R6/2 HD mouse model throughout the disease progression. Utilizing novel BimEL phospho-mutants we demonstrated the phosphorylation of Ser65 to be important for the stabilization of BimEL. We provided evidence that impaired proteasome function, increased JNK activity and reduced striatal BDNF lead to changes in the phosphorylation of BimEL, thereby promoting its stabilization specifically within the striatum of R6/2 mice. Furthermore, knocking down BimEL expression prevented mHtt-induced cell death in a HD cell culture. Taken together, these findings suggest that BimEL may contribute to the selective neurodegeneration and pathogenesis of HD.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3355556
- Subject Headings
- Huntington's chorea, Pathophysiology, Huntington's chorea, Molecular aspects, Huntington's chorea, Genetic aspects, Nervous system, Degeneration, Pathophysiology, Nervous system, Degeneration, Molecular aspects, Glutamine, Pathophysiology
- Format
- Document (PDF)
- Title
- The use of novel HDACi's for treatment of memory impairment in a mouse model of Alzheimer's disease.
- Creator
- Moyes, Jonathan., Harriet L. Wilkes Honors College
- Abstract/Description
-
Alzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory...
Show moreAlzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory in a mouse model of Alzheimer's disease. By use of a fear conditioning paradigm, we have shown that these HDACI's increase memory in AD mice, but show either no effect or a positive effect in wild-type mice. Future experiments will investigate the efficacy of compound 966 and the spine density of hippocampal brain slices after fear conditioning trials.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3359315
- Subject Headings
- Alzheimer's disease, Chemotherapy, Pharmacogenetics, Histone deacetylase, Inhibitors, Nervous system, Degeneration, Molecular aspects
- Format
- Document (PDF)
- Title
- New insights into the neuromodulatory role and potential action site of taurine in retinal neurons.
- Creator
- Bulley, Simon, Charles E. Schmidt College of Science, Department of Biomedical Science
- Abstract/Description
-
Taurine is the second most abundant amino acid in the CNS after glutamate and its functions have been found largely related to intracellular calcium ([Ca2+]i) modulation, osmoregulation, membrane stabilization, reproduction and immunity. The action of taurine has also been implicated in neurotransmission and neuromodulation though its specific sites of action are not fully understood. Isolated retinal neurons from the larval tiger salamanders (Ambystoma tigrinum) were used as a model to study...
Show moreTaurine is the second most abundant amino acid in the CNS after glutamate and its functions have been found largely related to intracellular calcium ([Ca2+]i) modulation, osmoregulation, membrane stabilization, reproduction and immunity. The action of taurine has also been implicated in neurotransmission and neuromodulation though its specific sites of action are not fully understood. Isolated retinal neurons from the larval tiger salamanders (Ambystoma tigrinum) were used as a model to study the neuromodulatory role of taurine in the CNS and to gain insights into its potential sites of action. A combination of techniques was used, including whole-cell patch clamp recording to study taurine's regulation of voltage-gated potassium (K+) and Ca2+ channels and Fluo-4AM Ca2+-imaging to study taurine's regulation of glutamate-induced [Ca2+] I,. Taurine was shown to suppress of glutamate-induced [Ca2+] l, in a dose dependent manner. This suppression was mostly sensitive to the glycine rece ptor antagonist Strychnine but insensitive to any GABA receptor antagonist. The remaining strychnine-insensitive effect was inhibited with the protein kinase A (PKA) inhibitor, PKI, suggesting that there was an additional metabotropic pathway. Moreover, using the protein kinase C (PKC) inhibitor, GF109203X, there was an enhancement in strychnine-insensitive taurine's regulation. Taurine inhibits voltage-gated Ca2+ channels in the retinal neurons and has a dual effect on voltage-gated K+ channels. Taurine causes an increase in K+ current amplitude which is further enhanced with PKI and blocked with GF109203X, suggesting that it is through a PKC-dependent pathway negatively controlled by PKA-dependent pathway., There is a suppression of K+ current by taurine with intracellular application of GF109203X, suggesting that the reduction is through a PKA-dependent pathway. With both PKC and PKA inhibitors there is no longer an enhancement in maximum amplitude but a shift of volt dependence on a hyperpolarizing direction. Taurine's enhancement of K+ current is blocked by the Kv1.3 subtype antagonist Margatoxin, with Kv1.3 accounting for the majority of delayed-rectifier sustained current in bipolar and amacrine cells, as well as 50% of ganglion cells. Interestingly, the enhancement of K+ current by taurine is blocked by 5HT2A antagonist MDL11939, suggesting that activation of PKC is through this metabotropic serotonin receptor subtype. The suppression of voltage-gated Ca2+ channels is reversed with a combination of MDL11939 and the 5HT1A antagonist NAN-190. These results provide the evidence that the natural effect of taurine in the retinal neurons might be dependent on the activation of both 5HT1A and 5HT2A receptors. The high apparent activity of taurine on 5HT receptors could have important implication for the actions of taurine in central brain in which taurine has been known to be beneficial for improving mental health, as well as learning and memory processes.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2953206
- Subject Headings
- Biological transport, Eye, Physiology, Taurine, Physiological effect, Taurine, Therapeutic use, Central nervous system, Physiology
- Format
- Document (PDF)
- Title
- The effect of ambient temperature on serotonin syndrome.
- Creator
- Krishnamoorthy, Swapna., Charles E. Schmidt College of Medicine
- Abstract/Description
-
Serotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and...
Show moreSerotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and prefrontal cortex (PFC), in particular, are sensitive to changes in ambient temperature (Tamb). The toxic increase of 5-HT is postulated to occur due to the temperature-dependent activation of these receptors that promotes a positive feedback mechanism. Our results suggest that changes in Tamb can either exacerbate or alleviate the symptom and that this is mediated by the 5-HT2A receptors. Understanding the mechanism involved in elevating Tcor is imperative in treating and preventing the disorder.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/186297
- Subject Headings
- Serotoninergic mechanisms, Central nervous system, Physiology, Body temperature, Regulation, Neurotransmitter receptors, Serotonin, Physiological effect
- Format
- Document (PDF)
- Title
- A study on neural conduction as in myelinated structure under pathological conditions.
- Creator
- Morales, George J., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
- Abstract/Description
-
A method for modeling and simulating neural action potential (AP) propagation along the length of an axon containing a number of Ranvier nodes is proposed in this dissertation. A system identification approach is adopted to represent node of Ranvier (NR) response to current pulse stimulus in the form of transfer function representations for NR excitability. Segments of myelinated internodal (IN) and NR regions are cascaded, representing the remaining downstream axon after a site-of-stimulus...
Show moreA method for modeling and simulating neural action potential (AP) propagation along the length of an axon containing a number of Ranvier nodes is proposed in this dissertation. A system identification approach is adopted to represent node of Ranvier (NR) response to current pulse stimulus in the form of transfer function representations for NR excitability. Segments of myelinated internodal (IN) and NR regions are cascaded, representing the remaining downstream axon after a site-of-stimulus introduction of an external current pulse. This cascading network is used to simulate "cable" properties and signal propagation along the length of the axon. This work proposes possible solutions to attenuation losses inherited in the classical myelinated cable models and accounts for neuronal AP velocity as well as introducing signal attenuation and transient delays associated with internodal demyelination. This model could aide as a predictive tool for the diagnosis and analysis of axonal signal integrity associated with demyelination pathology. Possible applications could include functional stimulation control methodologies for axon bundles that may exhibit signal fidelity issues associated with demyelination. It is further proposed that this model may serve as an instructive tool for further development and incorporation of other axon dynamic behaviors such as: relative refractory periods of AP generation, NR AP recovery mechanisms and responses to varied current stimulus input.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3171723
- Subject Headings
- Nervous system, Diseases, Research, Demyelination, Nodes of Ranvier, Neuromuscular diseases, Research
- Format
- Document (PDF)
- Title
- Neuroprotection from induced glutamate excitotoxicity by Conus brunneus conopeptides in a stroke-related model.
- Creator
- Crouch, Rebecca A., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Cone snails are carnivorous marine mollusks, utilizing their neuropeptide-rich venom for prey capture. The venom of Conus brunneus, a wide-spread Eastern Pacific vermivore, has not been extensively studied. In the current work, peptides from the dissected venom were characterized and tested using preliminary bioassays. Six peptides (A-F) were isolated and tested. Three peptide identities were determined by comparison with previously reported data: bru9a (A), bru3a (F), and an a-conotoxin (E)....
Show moreCone snails are carnivorous marine mollusks, utilizing their neuropeptide-rich venom for prey capture. The venom of Conus brunneus, a wide-spread Eastern Pacific vermivore, has not been extensively studied. In the current work, peptides from the dissected venom were characterized and tested using preliminary bioassays. Six peptides (A-F) were isolated and tested. Three peptide identities were determined by comparison with previously reported data: bru9a (A), bru3a (F), and an a-conotoxin (E). Preliminary screening in a stroke-related model of induced glutamate excitotoxicity in primary neuronal cells and PC12 cell cultures indicated potential neuroprotective activity of peptide fractions A, D, and F. Further testing is necessary to determine and verify structure, activity, target, and mechanism of action of the promising peptides from C. brunneus, which may prove effective neuropharmacological agents to treat stroke.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362331
- Subject Headings
- Gastropoda, Venom, Therapeutic use, Peptides, Structure, Neuroprotective agents, Central nervous system, Diseases, Treatment
- Format
- Document (PDF)
- Title
- Presynaptic Determinants of Synaptic Strength and Energy Efficiency at Drosophila Neuromuscular Junctions.
- Creator
- Lu, Zhongmin, Macleod, Gregory, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Changes in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is...
Show moreChanges in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is not known how PAZ and N are rebalanced during synaptic homeostasis to accomplish circuit stability. To address this knowledge gap, we adapted a neurophysiological experimental system consisting of two functionally differentiated glutamatergic motor neurons (MNs) innervating the same target. Average PAZ varied between nerve terminals, motivating us to explore benefits for high and low PAZ, respectively. We speculated that high PAZ confers high-energy efficiency. To test the hypothesis, electrophysiological and ultrastructural measurements were made. The terminal with the highest PAZ released more neurotransmitter but it did so with the least total energetic cost. An analytical model was built to further explore functional and structural aspects in optimizing energy efficiency. The model supported that energy efficiency optimization requires high PAZ. However, terminals with low PAZ were better able to sustain neurotransmitter release. We suggest that tension between energy efficiency and stamina sets PAZ and thus determines synaptic strength. To test the hypothesis that nerve terminals regulate PAZ rather than N to maintain synaptic strength, we induced sustained synaptic homeostasis at the nerve terminals. Ca2+ imaging revealed that terminals of the MN innervating only one muscle fiber utilized greater Ca2+ influx to achieve compensatory neurotransmitter release. In contrast, morphological measurements revealed that terminals of the MN inner vating multiple postsynaptic targets utilized an increase in N to achieve compensatory neurotransmitter release, but this only occurred at the terminal of the affected postsynaptic target. In conclusion, this dissertation provides several novel insights into a prominent question in neuroscience: how is synaptic strength established and maintained. The work indicates that tension exists between energy efficiency and stamina in neurotransmitter release likely influences PAZ. Furthermore, PAZ and N are rebalanced differently between terminals during synaptic homeostasis.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004519, http://purl.flvc.org/fau/fd/FA00004519
- Subject Headings
- Drosophila melanogaster--Nervous system., Drosophila melanogaster--Cytogenetics., Fruit-flies--Development., Fruit-flies--Nervous system., Genetic transcription., Transcription factors., Cellular signal transduction., Cellular control mechanisms., Myoneural junction.
- Format
- Document (PDF)
- Title
- Polyglutamine aggregates stimulate ER stress and trigger apoptosis by activating BH-3 only protein Bim.
- Creator
- Bhagavatula, Nithya, Wei, Jianning, Florida Atlantic University
- Abstract/Description
-
Huntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in...
Show moreHuntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in mitochondria is poorly understood. In the present study, we identified Bim (Bcl-2 interacting mediator of cell death) as the essential protein. We first established a cellular model of HD by over expressing the Nterminus of wild type and mutant Htt into HEK293 cell lines. We showed that the accumulation and aggregation of misfolded mutant Htt protein triggers ER stress and apoptosis. The Bim protein expression level was greatly increased in mutant Htt transfected cells and this increase was partially due to up-regulation of Bim mRNA as analyzed using quantitative RT-PCR. We further showed that Bim phosphorylation also played an important role in regulating Bim expression. Moreover, up-regulation of Bim facilitates the translocation of Bax to mitochondrial membrane, which lead to cytochrome c release and apoptosis. We also silenced Bim using siRNA to further investigate the essential role of Bim in mutant Htt induced ER stress and apoptosis. Identifying the Bim pathway that is altered in response to the mutant Htt protein is important for understanding the cellular processes impacted by the disease.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fau/fd/FA00000726
- Subject Headings
- Nervous system--Degeneration--Molecular aspects, Apoptosis, Cellular signal transduction, Huntington's disease--Genetic aspects, Huntington's disease--Pathophysiology
- Format
- Document (PDF)
- Title
- Effect of MDMA abuse on axonal transportation of serotonergic nervous system in the rat brain.
- Creator
- Adams, Herbert D., Ma, Zhiyuan, Tao, Rui
- Date Issued
- 2012-04-06
- PURL
- http://purl.flvc.org/fcla/dt/3348609
- Subject Headings
- N-Methyl-3,4-methylenedioxyamphetamine, Ecstasy, Receptors, Serotonin - drug effects, Serotonergic nervous system, Substance-related disorders, Methamphetamine --adverse effects, Serotonin --pharmacokinetics
- Format
- Document (PDF)
- Title
- The synergistic effects of concurrent stress on the inflammatory response in healthy individuals.
- Creator
- McAlpine, David, Huang, Chun-Jung
- Date Issued
- 2012-04-06
- PURL
- http://purl.flvc.org/fcla/dt/3349030
- Subject Headings
- Pentraxin 3, Inflammation, PTX3 protein, Vascular Diseases, Blood Vessels, C-Reactive Protein, Inflammation --blod, Parasympathetic Nervous System, Stress --psychological
- Format
- Document (PDF)
- Title
- Roles of serotonin 2A receptor in a serotonin syndrome.
- Creator
- Zhang, Gongliang, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Serotonin (5-HT) is a neurotransmitter in the central nervous system. Decrease in the brain 5-HT level could induce depression, showing a state of low mood, aversion to motion and feeling of worthlessness. About 12 million adults in the United States have depression. Antidepressants, such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors, can alleviate the depressive mood by increasing the brain's 5-HT activity, however they can also induce a potentially life...
Show moreSerotonin (5-HT) is a neurotransmitter in the central nervous system. Decrease in the brain 5-HT level could induce depression, showing a state of low mood, aversion to motion and feeling of worthlessness. About 12 million adults in the United States have depression. Antidepressants, such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors, can alleviate the depressive mood by increasing the brain's 5-HT activity, however they can also induce a potentially life-threatening side effect, namely 5-HT syndrome. This syndrome is manifested by neuromuscular hyperactivities, mental disorders and autonomic dysfunctions. Clinical studies have demonstrated that 5-HT2A receptor antagonists could effectively block severe symptoms of patients with the 5-HT syndrome. To understand the underlying mechanisms, in this study we examined the activity of the 5-HT2A receptor in rats with the 5-HT syndrome evoked by a combined injection of clorgyline, a monoamine oxidase inhibitor , and paroxetine, a selective 5-HT reuptake inhibitor. The major findings from my study were that: (1) Chronic clorgyline treatment significantly exacerbated 5-HT2A receptor-mediated symptoms of the 5-HT syndrome animals; (2) The 5-HT2A receptor-mediated symptoms were also aggravated when the 5-HT syndrome animals were housed in warm (32 ÀC) ambient temperature; (3) Blocking 5-HT2A receptors in the medial prefrontal cortex alleviated the 5-HT syndrome through a circuit between raphe serotonergic neurons and medial prefrontal cortex glutamatergic neurons. Taken together, my data demonstrate that the activity of 5-HT2A receptors may be enhanced by chronic antidepressant treatment and warm environmental temperature., The sensitized 5-HT2A receptor in the medial prefrontal cortex may exacerbate the syndrome through a positive-feedback circuit between medial prefrontal cortex and raphe nuclei, which would result in excessive 5-HT in the brain. This study casts a new light on the underlying mechanisms of the 5-HT syndrome.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2100576
- Subject Headings
- Serotonin uptake inhibitors, Therapeutic use, Serotonin uptake inhibitors, Physiological effect, Serotonin, Receptors, Physiological effect, Central nervous system, Physiology, Neurotransmitter receptors, Serotoninergic mechanisms
- Format
- Document (PDF)
- Title
- Over-Expression of BDNF Does Not Rescue Sensory Deprivation-Induced Death of Adult-Born Olfactory Granule Cells.
- Creator
- Berger, Rachel A., Guthrie, Kathleen M., Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
It is of interest to understand how new neurons incorporate themselves into the existing circuitry of certain neuronal populations. One such population of neurons is that which are born in the subventricular zone (SVZ) and migrate to the olfactory bulb where they differentiate into granule cells. Another area of interest is the role of brain-derived neurotrophic factor (BDNF) on the survival and overall health of these neurons. This study aimed to test whether or not BDNF is a survival factor...
Show moreIt is of interest to understand how new neurons incorporate themselves into the existing circuitry of certain neuronal populations. One such population of neurons is that which are born in the subventricular zone (SVZ) and migrate to the olfactory bulb where they differentiate into granule cells. Another area of interest is the role of brain-derived neurotrophic factor (BDNF) on the survival and overall health of these neurons. This study aimed to test whether or not BDNF is a survival factor for adult-born granule cells. Here were utilized a transgenic mouse model over-expressing BDNF under the α- calcium/calmodulin-dependent protein kinase II (CAMKIIα) promoter, and tested its effect on olfactory granule cells under sensory deprived conditions. Results from this experiment indicated that there was no significant difference in cell death or cell survival when comparing transgenic and wild type animals. We concluded that BDNF is not a survival factor for adult-born granule cells.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004722, http://purl.flvc.org/fau/fd/FA00004722
- Subject Headings
- Cellular control mechanisms, Mice as laboratory animals, Nervous system -- Diseases -- Gene therapy, Neural circuitry, Neuroplasticity, Neurotransmitter receptors, Sensory deprivation, Sensory neurons -- Testing
- Format
- Document (PDF)
- Title
- Afferent projections to rhomboid nucleus of thalamus.
- Creator
- Owens, Michelle Ann, Florida Atlantic University, Vertes, Robert P.
- Abstract/Description
-
The midline thalamus of rats is anatomically and functionally part of the "limbic" thalamus. The midline thalamic rhomboid nucleus (RH) has not been well characterized. The rhomboid nucleus is located just dorsal to the reuniens nucleus (RE), and just ventral to the central medial nucleus (CeM) of the thalamus. Using the retrograde tracer fluorogold (FG) and anti-FG antibody, we examined afferent projections to RH in the rat. Control injections were also made in CeM and the submedial nucleus...
Show moreThe midline thalamus of rats is anatomically and functionally part of the "limbic" thalamus. The midline thalamic rhomboid nucleus (RH) has not been well characterized. The rhomboid nucleus is located just dorsal to the reuniens nucleus (RE), and just ventral to the central medial nucleus (CeM) of the thalamus. Using the retrograde tracer fluorogold (FG) and anti-FG antibody, we examined afferent projections to RH in the rat. Control injections were also made in CeM and the submedial nucleus of thalamus (SMT). The main sources of input to RH were from the anterior cingulate, agranular insular, orbital, and somatosensory cortices; the claustrum; the reticular nucleus of the thalamus; the posterior hypothalamus; and various brainstem structures. Based on patterns of the afferent projections, the role of RH in arousal, attention, and mnemonic functions is discussed.
Show less - Date Issued
- 2005
- PURL
- http://purl.flvc.org/fcla/dt/13220
- Subject Headings
- Rats as laboratory animals, Rats--Nervous system, Thalamus--Research, Rats--Embryology, Afferent pathways, Perceptual-motor processes, Sensorimotor integration
- Format
- Document (PDF)
- Title
- Role of taurine in the central nervous system.
- Creator
- Wu, Jang-Yen, Prentice, Howard
- Date Issued
- 2010-08-24
- PURL
- http://purl.flvc.org/fau/fd/FADT3327262
- Subject Headings
- Central Nervous System --metabolism, Glutamic Acid --metabolism, Homeostasis --physiology, Neuroprotective Agents --metabolism, Neurotransmitter Agents --metabolism, Proto-Oncogene Proteins c-bcl-2 --metabolism, Receptors, Neurotransmitter --metabolism, Signal Transduction --physiology, Taurine, Taurine --metabolism, Neuroprotective Agents, Neurotransmitter Agents
- Format
- Document (PDF)