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Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan 2018 The University of Western Ontario

Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan

Electronic Thesis and Dissertation Repository

The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in ...


Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein 2018 University of Massachusetts Medical School

Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease characterized by motor neuron loss. Although pathological mutations exist in >15 genes, the mechanism(s) underlying ALS are unknown. FUS is one such gene and encodes the nuclear RNA-binding protein (RBP), fused in sarcoma (FUS), which actively shuttles between the nucleus and cytoplasm. Intriguingly, nearly half of the ALS mutations identified in FUS cause this protein to mislocalize, suggesting that FUS localization is relevant to disease.

Here, we found that excitotoxicity, a neuronal stress caused by aberrant glutamate signaling, induces the rapid redistribution of FUS and additional disease-linked RBPs ...


Synaptic Correlates For Stress Sensitization, Julia KJ Sunstrum 2018 The University of Western Ontario

Synaptic Correlates For Stress Sensitization, Julia Kj Sunstrum

Electronic Thesis and Dissertation Repository

The stress response is essential for survival, but it can be detrimental when persistently activated during chronic stress. Therefore, the magnitude of the stress response must be finely-tuned in order to be adaptive. Indeed, an animal’s stress response system normally undergoes habituation that decreases responses to a repeated, familiar stressor. Importantly, the same animal still responds normally, or even becomes sensitized, to an unfamiliar (novel) stressor. This indicates that chronic stress simultaneously induces two opposing types of plasticity, one that underlies habituated responses and another that drives sensitized responses. The activation of the hypothalamic-pituitary-adrenal (HPA) axis — a hallmark of ...


Integrated Analysis Of Mirna/Mrna Expression In The Neurocircuitry Underlying Nicotine Dependence, Alison P. Casserly 2018 University of Massachusetts Medical School

Integrated Analysis Of Mirna/Mrna Expression In The Neurocircuitry Underlying Nicotine Dependence, Alison P. Casserly

GSBS Dissertations and Theses

Nicotine dependence is responsible for perpetuating the adverse health effects due to tobacco use, the leading cause of preventable death worldwide. Nicotine is an agonist for nicotinic acetylcholine receptors, which are enriched in the mesocorticolimbic and habenulo-interpeduncular circuitries, underlying nicotine reward and withdrawal, respectively. Drugs of abuse, including nicotine, induce stable neuroadaptations, requiring protein synthesis through regulation of transcription factors, epigenetic mechanisms, and non-coding RNAs. It also been shown that miRNAs in brain are regulated by nicotine and that miRNA dysregulation contributes to brain dysfunction, including drug addiction. While much is known about the neurocircuitry responsible for the behaviors associated ...


Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells, Shigeru Yamada, Yusuke Kubo, Daiju Yamazaki, Yuko Sekino, Yoko Nomura, Sachiko Yoshida, Yusunari Kanda 2018 National Institute of Health Sciences

Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells, Shigeru Yamada, Yusuke Kubo, Daiju Yamazaki, Yuko Sekino, Yoko Nomura, Sachiko Yoshida, Yusunari Kanda

Publications and Research

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the ...


The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral ...


Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., Guela Sokhadze 2018 University of Louisville

Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., Guela Sokhadze

Electronic Theses and Dissertations

Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or ...


Cholinergic Control Of Cortical Circuit Activity, Rajan Dasgupta 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Cholinergic Control Of Cortical Circuit Activity, Rajan Dasgupta

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Cholinergic neurons of the basal forebrain send extensive projections to all regions of the neocortex and are critically involved in a diverse array of cognitive functions, including sensation, attention and learning. Cholinergic signaling also plays a crucial role in the moment-to-moment control of ongoing cortical state transitions that occur during periods of wakefulness. Yet, the underlying circuit mechanisms of synaptic cholinergic function in the neocortex remain unclear. Moreover, acetylcholine continues to be widely viewed as a slow and diffuse neuromodulator, despite the preponderance of in vivo evidence demonstrating rapid cholinergic function. In this study, we used a combination of optogenetics ...


Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa 2018 Kennesaw State University

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like ...


Neurexin Directs Partner-Specific Synaptic Connectivity In C. Elegans, Alison Philbrook, Shankar Ramachandran, Christopher M. Lambert, Devyn Oliver, Jeremy Florman, Mark J. Alkema, Michele Lemons, Michael M. Francis 2018 University of Massachusetts Medical School

Neurexin Directs Partner-Specific Synaptic Connectivity In C. Elegans, Alison Philbrook, Shankar Ramachandran, Christopher M. Lambert, Devyn Oliver, Jeremy Florman, Mark J. Alkema, Michele Lemons, Michael M. Francis

Open Access Articles

In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in C. elegans as a model. We report that C. elegans nrx-1/neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles. We show that cholinergic outputs onto neurons are, unexpectedly, located at previously undefined spine-like protrusions from GABAergic dendrites. Both these spine-like features and cholinergic receptor clustering are strikingly disrupted in the absence of nrx-1. Excitatory transmission onto GABAergic neurons, but not neuromuscular transmission, is also disrupted. Our ...


Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, Owen M. Peters, Elizabeth A. Lewis, Jeannette M. Osterloh, Alexandra Weiss, Johnny Salameh, Jake P. Metterville, Robert H. Brown Jr., Marc R. Freeman 2018 University of Massachusetts Medical School

Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, Owen M. Peters, Elizabeth A. Lewis, Jeannette M. Osterloh, Alexandra Weiss, Johnny Salameh, Jake P. Metterville, Robert H. Brown Jr., Marc R. Freeman

Neurobiology Publications

Axon degeneration occurs in all neurodegenerative diseases, but the molecular pathways regulating axon destruction during neurodegeneration are poorly understood. Sterile Alpha and TIR Motif Containing 1 (Sarm1) is an essential component of the prodegenerative pathway driving axon degeneration after axotomy and represents an appealing target for therapeutic intervention in neurological conditions involving axon loss. Amyotrophic lateral sclerosis (ALS) is characterized by rapid, progressive motor neuron degeneration and muscle atrophy, causing paralysis and death. Patient tissue and animal models of ALS show destruction of upper and lower motor neuron cell bodies and loss of their associated axons. Here, we investigate whether ...


Effort-Related Motivational Dysfunctions: Behavioral And Neurochemical Studies Of The Wistar-Kyoto Rat Model Of Depression, Brendan Abbott 2018 University of Massachusetts Amherst

Effort-Related Motivational Dysfunctions: Behavioral And Neurochemical Studies Of The Wistar-Kyoto Rat Model Of Depression, Brendan Abbott

Masters Theses

Depression and related disorders are characterized by motivational dysfunctions, including deficits in behavioral activation and exertion of effort. Animal models of relevance to depression represent a critical starting point in elucidating the neurobiological mechanisms underlying motivational dysfunctions. The present study explored the use of the Wistar-Kyoto (WKY) animal model of depression to examine effort-related functions as measured by voluntary wheel running and performance on a mixed fixed ratio 5/progressive ratio (FR5/PR) operant task. Given the known link between activational aspects of motivation and the mesocorticolimbic dopamine (DA) system, the behavioral effects of d-amphetamine (0.5 and 1.0 ...


Role Of Stip1 In Tdp-43 Mediated Toxicity And Proteinopathy In Neurodegenerative Disorders, Abdul Razzaq 2018 The University of Western Ontario

Role Of Stip1 In Tdp-43 Mediated Toxicity And Proteinopathy In Neurodegenerative Disorders, Abdul Razzaq

Electronic Thesis and Dissertation Repository

A common hallmark of neurodegenerative disorders is the abnormal aggregation of misfolded proteins. Aggregates of phosphorylated TAR-DNA-binding protein-43 (TDP-43) are found in multiple neurodegenerative disorders. The molecular chaperones Hsp70 and Hsp90 have been shown to be key modulators of TDP-43 phosphorylation and expression, however the mechanisms behind how this interaction occur are unclear. Stress-Inducible PhosphoProtein 1 (STIP1) is a critical co-chaperone linking Hsp90 to Hsp70 to modulate chaperone client stability. In this study, we evaluated the potential role of STIP1 in TDP-43 stability and cellular toxicity. We demonstrated that STIP1 interacts with TDP-43 and the deletion of STIP1 leads to ...


Endocytosis And The Nitric Oxide-Dependent Release Of Chloride, Vernon K. Dunn Jr 2018 Louisiana State University and Agricultural and Mechanical College

Endocytosis And The Nitric Oxide-Dependent Release Of Chloride, Vernon K. Dunn Jr

LSU Doctoral Dissertations

Understanding the regulation of retinal synapses is a key step in elucidating the processing of information in the retina. Our lab has previously shown that nitric oxide (NO) can alter the synaptic response properties of amacrine cells by releasing Cl- from internal acidic compartments. This alteration in the Cl- gradient brings about a positive shift in the reversal potential of the GABA-gated current, which can convert inhibitory synapses into excitatory synapses. Recently, we have shown that the cystic fibrosis transmembrane regulator (CFTR) Cl- channel is involved in the Cl- release. Here, we test the hypothesis that (acidic) synaptic vesicles are ...


Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully APC Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins 2018 University of Texas at El Paso

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins

Arshad M. Khan, Ph.D.

This article, which includes novel unpublished data along with commentary and analysis,
focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from
brain tissue to the original locations within the brain that they are derived from using digital atlas
mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic
analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we
highlight studies that have mined biochemical and molecular information from the hypothalamus
and then lay out a strategy for how these data can be linked spatially to the mapped locations in a
canonical brain atlas ...


Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, María E. Solesio, Pablo M. Peixoto, Ludovic Debure, Stephen M. Madamba, Mony J. de Leon, Thomas Wisniewski, Evgeny V. Pavlov, Silvia Fossati 2018 New York University

Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, María E. Solesio, Pablo M. Peixoto, Ludovic Debure, Stephen M. Madamba, Mony J. De Leon, Thomas Wisniewski, Evgeny V. Pavlov, Silvia Fossati

Publications and Research

Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer’s disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid b (Ab)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Ab, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Ab, without affecting metabolic function. ATZ was effective at concentrations 10 times ...


Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng 2018 Central South University

Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng

Open Access Articles

EphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis ...


Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas 2018 Washington University in St. Louis

Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas

Engineering and Applied Science Theses & Dissertations

Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor ...


Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, Robert A. Mans, Kyle D. Hinton, Amanda E. Rumer, Kourtnei A. Zellner, Emily A. Blankenship, Lia M. Kerkes, Michael J. Hamilton, Theresa R. Reilly, Cicely H. Payne 2018 Georgia Southern University - Armstrong

Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, Robert A. Mans, Kyle D. Hinton, Amanda E. Rumer, Kourtnei A. Zellner, Emily A. Blankenship, Lia M. Kerkes, Michael J. Hamilton, Theresa R. Reilly, Cicely H. Payne

Georgia Journal of Science

Zebrafish are a powerful research tool in the field of neuroscience, offering several logistical and physiological advantages over rodents as a research model. However, the molecular dynamics of this model organism, especially with regards to learning and memory, are scarcely known. The current study explored the zebrafish brain for the presence of a protein bearing a similar function to the activity-regulated, cytoskeleton-associated protein (Arc), a critical player in synaptic plasticity. The adult zebrafish brain was found to express a protein with immunoreactivity against the anti-Arc antibody H-300. Immunoreactivity was detected ubiquitously, especially in areas known as adult progenitor cell zones ...


Precision Gene Therapy For Charcot-Marie-Tooth Disease: From Identifying Genetic Modifiers To Developing Allele-Specific Therapies, Kathryn H. Morelli Ph.D. 2018 The University of Maine

Precision Gene Therapy For Charcot-Marie-Tooth Disease: From Identifying Genetic Modifiers To Developing Allele-Specific Therapies, Kathryn H. Morelli Ph.D.

Electronic Theses and Dissertations

Charcot-Marie-Tooth Disease (CMT) is a clinically and genetically heterogeneous collection of inherited peripheral neuropathies generally characterized by progressive muscle atrophy, weakness, and loss of sensation in the distal extremities. This inherited disorder, for which there is currently no curative treatment, is the most common inherited disease of the peripheral nervous system, affecting 1:2,500 individuals worldwide.

Clinically, CMT is broadly divided into demyelinating (type 1) and axonal (type 2) forms. Although the clinical presentation can vary greatly in severity and progression within individual patients. Genetically, over 1,000 mutations in over 80 loci in the human genome have been ...


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