Search results

Title: Pathology at the neuromuscular junction in mouse models of spinal bulbar muscular atrophy
Creator: Poort, Jessica Erin
Date: 2014
Collection: Electronic Theses & Dissertations
Description: Spinal bulbar muscular atrophy (SBMA) is a progressive, late onset neuromuscular disease that results in muscle weakness and atrophy, as well as motoneuron death in men. While pathology at the neuromuscular junction (NMJ) is noted in numerous neurodegenerative diseases, disease-related changes at the NMJ in SBMA have not been explored. Characterizing such changes is not only important for determining whether the NMJ has any role in the functional changes underlying motor dysfunction, but also...
Show moreSpinal bulbar muscular atrophy (SBMA) is a progressive, late onset neuromuscular disease that results in muscle weakness and atrophy, as well as motoneuron death in men. While pathology at the neuromuscular junction (NMJ) is noted in numerous neurodegenerative diseases, disease-related changes at the NMJ in SBMA have not been explored. Characterizing such changes is not only important for determining whether the NMJ has any role in the functional changes underlying motor dysfunction, but also in determining how such potential pathology at the NMJ develops as disease progresses. If for example, pathology emerges first at the NMJ followed by motoneuron death, then the NMJ offers future promise as a therapeutic target for preventing or reversing symptoms of SBMA before motoneurons are lost. We evaluated three different mouse models of SBMA, one overexpressing a wildtype androgen receptor (AR) exclusively in muscle fibers (so called "myogenic" model), a second which expressed the endogenous AR gene with the first exon of the human mutant AR gene "knocked in" (the so called "knock-in" model), and a final model that broadly expresses a full length human AR transgene harboring the SBMA mutation (the so called "97Q" model). Using both confocal microscopy and electron microscopy, I found that all three mouse models show a pathological fragmentation of the NMJ suggestive of functionally weakened synapses. Other changes at the neuromuscular synapse suggesting decreases in synaptic strength that were found in some but not all models include a decline in the number of docked vesicles ready for release in nerve terminals, a widening of synaptic clefts, simplified postsynaptic folds, and an abnormal accumulation of synaptic vesicle and neurofilament proteins. Retrograde axonal transport of endosomes was also characterized in the 97Q model using live imaging confocal microscopy. Despite previously published data, I found no evidence for a disease-related defect in retrograde transport in the 97Q model. The strikingly abnormal morphology of NMJs in all three models raises the possibility that synaptic function is impaired. Such synaptic dysfunction may contribute to or underlie the impairments in motor function associated with SBMA.
Show less

Title: ROLE OF VENTRAL TEGMENTAL AREA NEUROTENSIN RECEPTOR-1 NEURONS IN ENERGY BALANCE
Creator: Perez-Bonilla, Patricia
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Dopamine (DA) neurons in the ventral tegmental area (VTA) modulate physical activity and feeding behaviors that are disrupted in obesity. Although the heterogeneity of VTA DA neurons has hindered determination of which ones might be leveraged to support weight loss, we have characterized a subset of VTA DA neurons that express NtsR1 (VTA NtsR1 neurons) that are involved in the coordination of energy balance. We hypothesized that 1) increased activity VTA NtsR1 neurons might promote weight...
Show moreDopamine (DA) neurons in the ventral tegmental area (VTA) modulate physical activity and feeding behaviors that are disrupted in obesity. Although the heterogeneity of VTA DA neurons has hindered determination of which ones might be leveraged to support weight loss, we have characterized a subset of VTA DA neurons that express NtsR1 (VTA NtsR1 neurons) that are involved in the coordination of energy balance. We hypothesized that 1) increased activity VTA NtsR1 neurons might promote weight loss behaviors, and that 2) deleting NtsR1 specifically from VTA DA neurons would promote weight gain by increasing food intake and decreasing physical activity. We first used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate VTA NtsR1 neurons in normal weight and diet-induced obese mice.Acute activation of VTA NtsR1 neurons (24hr) significantly decreased body weight in normal weight and obese mice by reducing food intake and increasing physical activity. Moreover, daily activation of VTA NtsR1 neurons in obese mice sustained weight loss over 7 days. Activating VTA NtsR1 neurons also suppressed how much mice worked to obtain sucrose rewards, even when there was high motivation to consume. However, VTA NtsR1 neural activation was not reinforcing, nor did it invoke anxiety, vasodepressor responses or hypothermia. We then used newly generated NtsR1 flox/flox mice to study NtsR1 deletion in both development and adulthood. Curiously, developmental deletion of VTA NtsR1 (by crossing DAT Cre mice with NtsR1 flox/flox mice) had no impact on feeding or body weight. Adult deletion of the receptor (by injecting adeno associated Cre into VTA of adult NtsR1 flox/flox mice), however, resulted in lower body weight and DA-dependent food intake. Altogether, these data suggest that modulating NtsR1 expression in the adult VTA may be useful to safely promote weight loss, and that NtsR1 is worth further exploration for managing obesity.
Show less

Title: SEX AND PHENOTYPIC DIFFERENCES OF OBESITY-INDUCED GHSR VENTRAL HIPPOCAMPAL DISRUPTIONS IN THE CONTROL OF APPETITE
Creator: KONDILIS, ATHANASIOS
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The gastric hunger signal, ghrelin, influences feeding behavior via activation of the growth hormone secretagogue receptor (GHSR). GHSR’s are abundantly expressed in cells in the ventral hippocampus (VHPC) where they function to regulate food intake. In this study, we used a GHSR-IRES-Cre mouse to examine whether feeding behaviors driven by GHSR cells in the VHPC are influenced by vulnerability to dietary obesity. Both males and females were exposed to 8 weeks of a high fat diet (HFD)—the top...
Show moreThe gastric hunger signal, ghrelin, influences feeding behavior via activation of the growth hormone secretagogue receptor (GHSR). GHSR’s are abundantly expressed in cells in the ventral hippocampus (VHPC) where they function to regulate food intake. In this study, we used a GHSR-IRES-Cre mouse to examine whether feeding behaviors driven by GHSR cells in the VHPC are influenced by vulnerability to dietary obesity. Both males and females were exposed to 8 weeks of a high fat diet (HFD)—the top and bottom quartiles of weight gainers from each respective sex were designated as diet-induced obese (DIO) and diet resistant (DR), respectively. These mice received targeted injections of an excitatory (hM3Dq) or inhibitory DREADD (hM4Di) virus. This enabled chemogenetic control of GHSR-expressing cells in the VHPC as mice engaged in consumption of lab chow or HFD. Only DR female mice displayed the expected increase in food intake when tested with lab chow following DREADD stimulation, indicating that female mice that are resistant to dietary obesity maintain typical function for GHSR’s in VHPC. Surprisingly, in males, DREADD stimulation decreased meal intake, which for chow occurred in DIO mice, whereas for HFD testing this was observed in DR mice. On the other hand, DREADD inhibition attenuated chow intake only in female mice. In the final series of studies, I used licking microstructure to examine the pre-ingestive (e.g., orosensory, palatability) and post-ingestive (e.g., gastrointestinal negative feedback) variables that regulate GHSR-dependent food intake. Multiple findings were revealed, including that the increased consumption of food in female mice following GHSR stimulation reflects a reduction in gastrointestinal negative feedback. Overall, my findings stress the need to implement a rigorous examination of a host of variables with refined analyses of meal intake to determine a role for how feeding signals in the brain impact ingestive behavior.
Show less

Title: Sexual dimorphisms and androgen influence in medial posterodorsal amygdala astrocytes
Creator: Johnson, Ryan T.
Date: 2011
Collection: Electronic Theses & Dissertations
Description: The amygdala is a highly interconnected brain region involved in fear, anxiety, social and reproductive behaviors. In humans and laboratory species the amygdala exhibits sexual dimorphisms in neuroanatomy and function both in juveniles and adults. In rodents, the medial posterodorsal amygdala (MePD) is particularly sexually dimorphic and gonadal hormone sensitive, and while neurons have been examined in this region, few reports have examined the potential influence of gonadal hormones on...
Show moreThe amygdala is a highly interconnected brain region involved in fear, anxiety, social and reproductive behaviors. In humans and laboratory species the amygdala exhibits sexual dimorphisms in neuroanatomy and function both in juveniles and adults. In rodents, the medial posterodorsal amygdala (MePD) is particularly sexually dimorphic and gonadal hormone sensitive, and while neurons have been examined in this region, few reports have examined the potential influence of gonadal hormones on other cellular components of the MePD. Astrocytes are a subtype of glia involved in synapse formation and known to be plastic and dynamic cells sensitive to gonadal hormone influence in several brain regions. My dissertation reveals sexual dimorphisms in the number of astrocytes in the juvenile rat MePD and that this sexual dimorphism remains present in adult animals. I also found sex differences in the arbor complexity of astrocytes in adults that are not present prior to puberty. Astrocytes also respond to changes in circulating hormone levels in adulthood. Furthermore, while the sex difference in astrocyte numbers in juvenile animals is androgen receptor-independent, the sex differences found in adult astrocyte numbers and arbor complexity are both androgen receptor-dependent. Finally, I provide evidence that astrocytes in the MePD contain androgen receptors, suggesting that androgens may act directly on these cells. The influence of gonadal hormones on astrocytes in the MePD is likely an important part of pubertal development and has implications for our understanding of the cellular organization of the amygdala and its function.
Show less

Title: Structural connectivity of an interoception network in schizophrenia
Creator: Yao, Beier
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Interoception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also many cognitive processes, especially motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but its neural underpinning has not been examined. The current study aims to investigate the structural connectivity of a putative interoception network in schizophrenia, and its...
Show moreInteroception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also many cognitive processes, especially motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but its neural underpinning has not been examined. The current study aims to investigate the structural connectivity of a putative interoception network in schizophrenia, and its relationship with affective functioning and clinical symptoms. Thirty-five participants with schizophrenia (SZ) and 36 healthy control participants (HC) underwent diffusion tensor imaging (DTI) and performed tasks measuring emotional functioning. Probabilistic tractography was used to identify white matter tracts connecting the key hubs forming the interoception network (i.e., rostral and caudal anterior cingulate cortex, ventral anterior insula, dorsal mid and posterior insula, and amygdala). Microstructural integrity of these tracts was compared across groups and correlated with measures of emotional functioning and symptom severity. I found that SZ exhibited altered structural connectivity in the putative interoception network, compared to HC. The structural connectivity of the network was correlated with emotion recognition in HC, supporting a link between the interoception network and emotional functioning. However, this correlation was much weaker in SZ, suggesting less reliance on this network. I did not find a correlation between the structural connectivity and clinical symptoms in SZ. These findings suggest that altered interoception may play a role in illness mechanisms of schizophrenia, especially in relation to emotional deficits.
Show less

Title: THE PERSISTENT AND MULTIDIMENSIONAL MICROGLIAL RESPONSE TO PATHOLOGICAL ALPHA-SYNUCLEIN AGGREGATION
Creator: Stoll, Anna C.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Parkinson’s Disease, the second most common neurodegenerative disease, affects approximately 1 million people in the USA with 60,000 newly diagnosed people each year. Pathologically, PD is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies) and the progressive loss of the nigrostriatal dopamine (DA) neurons. While the exact cause of PD remains unknown, mounting evidence has suggested that neuroinflammation may play a significant role in PD...
Show moreParkinson’s Disease, the second most common neurodegenerative disease, affects approximately 1 million people in the USA with 60,000 newly diagnosed people each year. Pathologically, PD is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies) and the progressive loss of the nigrostriatal dopamine (DA) neurons. While the exact cause of PD remains unknown, mounting evidence has suggested that neuroinflammation may play a significant role in PD progression. The pathological features of PD can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy in rats. Specifically, in association with accumulation of phosphorylated α-syn (pSyn) inclusions in the SNpc, microglia increase soma size and MHC-II expression. This microglial response parallels pSyn inclusion formation, peaking at 2 months following intrastriatal PFF injection, months prior to the SNpc degeneration observed in the model. The overarching question of this dissertation is: does the microglial response to pathological α-syn accumulation contribute to degeneration? In Aim 1 of this dissertation an inhibitor of colony stimulating factor 1 receptor (CSF1R) was used to partially deplete microglia within the context of the α-syn PFF rat model in order to determine whether degeneration of the nigrostriatal system can be attenuated. Despite significant microglial depletion, increased soma size and expression of major-histocompatibility complex-II (MHC-II) on microglia within the α-syn inclusion bearing substantia nigra pars compacta (SNpc) was maintained. Further, partial microglia depletion did not impact degeneration of dopaminergic neurons in the SNpc. Paradoxically, long term partial microglial depletion increased the soma size of remaining microglia in both control and PFF rats was associated with widespread MHC-IIir expression in extranigral regions. These results suggest that partial microglial depletion is not a promising anti-inflammatory therapeutic strategy for PD and that this approach may induce a heightened proinflammatory state in remaining microglia. Aim 2 of this dissertation built on a previous study RNA-Seq dataset that identified multiple upregulated innate and adaptive immune transcripts in the inclusion bearing SNpc in the PFF model. Complementary approaches of fluorescent in situ hybridization (FISH) and droplet digital PCR (ddPCR) were used. FISH results identified an a-syn aggregate associated microglial (a-SAM) phenotype that is characterized by upregulation of CD74, CXCl10, RT1-A2, GRN, CSF1R, Tyrobp, C3, C1qa and Fcer1g. ddPCR results identified additional neuroinflammatory genes, Cd4, Stat1, Casp 1, Axl and IL18, that are significantly upregulated in inclusion bearing nigral tissue. Collectively these findings implicate that the deposition of pathological α-syn inclusions in the SNpc is associated with perturbations in immune functions related to complement, inflammasome and T cell activation, phagocytosis, and interferon gamma signaling. Collectively, the findings of these dissertation experiments demonstrate that the microglial response to pathological α-syn aggregation is persistent and multifaceted. This comprehensive understanding of the multidimensional response of microglia to pathological α-syn aggregates may help to uncover novel therapeutic targets that could facilitate future anti-inflammatory, disease-modifying strategies for PD.
Show less

Title: THE ROLE OF α-SYNUCLEIN IN CHOLINERGIC NEUROTRANSMISSION IN THE ENTERIC NERVOUS SYSTEM
Creator: Yelleswarapu, Narayana KrishnaChaithanya
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder that is manifested by significant motor impairments that decrease the quality of life and increase mortality in our elderly population. Non-motor symptoms in PD are common in patients and occur up to 2 decades prior to the onset of motor symptoms. Gastrointestinal (GI) complications, specifically constipation, is seen in over 50% of patients with PD and can be debilitating and result in malnutrition and weight loss....
Show moreParkinson’s disease (PD) is a slowly progressive neurodegenerative disorder that is manifested by significant motor impairments that decrease the quality of life and increase mortality in our elderly population. Non-motor symptoms in PD are common in patients and occur up to 2 decades prior to the onset of motor symptoms. Gastrointestinal (GI) complications, specifically constipation, is seen in over 50% of patients with PD and can be debilitating and result in malnutrition and weight loss. There is a need to elucidate the underlying mechanisms the lead to gut dysmotility in PD. Moreover, the pathologic event that causes cell death of dopaminergic neurons within the central nervous system (CNS) is observed with the enteric nervous system (ENS) decades prior to pathology in the CNS. This pathologic event is the toxic conversion and aggregation of a presynaptic terminal protein, α-synuclein (αSyn), into Lewy bodies. αSyn plays an important functional role in various cellular processes, including but not limited to, mitochondrial, lysosomal, synaptic vesicle regulation, and protease function. Therefore, we can predict the cascade of events that occur when this protein is no longer functional. Within the ENS, acetylcholine is the primary vesicular neurotransmitter involved in smooth muscle contractions. In this work I aimed to elucidate the role of pathologic αSyn on slow colonic transit disrupting cholinergic neurotransmission. In Chapter 2, we used two mouse models of hαSyn overexpression to target ENS pathology. In Chapter 3, we used a gene knockout of αSyn to further establish a functional role for the protein in cholinergic neurotransmission. We performed immunofluorescence, fecal pellet output, whole gut transit, colonic migrating motor complexes, studied longitudinal smooth muscle contractions, and junctional potentials to put together a thorough picture connecting phenotype to circuitry within the ENS. Our findings discussed in this dissertation shed light on 1) αSyn’s role in cholinergic neurotransmission, and 2) whether αSyn is necessary for normal colonic function and motility. Overall, cholinergic neurotransmission warrants a closer inspection in the ENS in PD. Strong evidence has continued to associate αSyn pathology to cholinergic neurons. Understanding this mechanism may allow for development of therapeutics that may alleviate GI symptoms in the PD population and help focus on discovering an early biomarker in diagnosing PD.
Show less

Title: TOWARD PRECISION MEDICINE : EFFECTS OF THE COMMON VAL66MET BDNF VARIANT IN THE AGING BRAIN AND IMPLICATIONS FOR THE FUTURE OF PARKINSON’S DISEASE THERAPEUTICS
Creator: Mercado-Idziak, Natosha Marie
Date: 2021
Collection: Electronic Theses & Dissertations
Description: The rs6265 (Val66Met) single nucleotide polymorphism in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that has been shown to alter therapeutic responses in patients with Parkinson’s disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF by disrupting BDNF transport and sorting into synaptic vesicles. In the experiments detailed in this thesis, I examine the effects of the Val66Met SNP, and its interaction...
Show moreThe rs6265 (Val66Met) single nucleotide polymorphism in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that has been shown to alter therapeutic responses in patients with Parkinson’s disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF by disrupting BDNF transport and sorting into synaptic vesicles. In the experiments detailed in this thesis, I examine the effects of the Val66Met SNP, and its interaction with aging, on therapeutic efficacy and the development of aberrant side-effects following primary dopamine (DA) neuron transplantation, a restorative experimental therapeutic approach for PD that is currently experiencing a robust revitalization following a decade-long worldwide moratorium. In particular, I hypothesized that rs6265-mediated dysfunctional BDNF signaling is an unrecognized contributor to the limited clinical benefit observed in a subpopulation of individuals with PD despite robust survival of grafted DA neurons and extensive integration into the host brain. I also hypothesized that this genetic variant contributes to the development of graft-induced dyskinesias (GID). To test these hypotheses, we generated a novel CRISPR knock-in rat model of the rs6265 BDNF SNP to investigate for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect burden in subjects grafted with embryonic ventral mesencephalic DA neurons. In two sister studies, I compared these primary endpoints between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met), in both young adult (8 m.o. at grafting) and middle-aged (15 m.o. at grafting) cohorts. In each study, rats were rendered unilaterally parkinsonian with intranigral 6-hydroxydopamine and primed with levodopa (12 mg/kg M-Fr) to induce stable expression of levodopa-induced dyskinesias (LID), the primary behavioral endpoint for assessing graft function. After levodopa priming, rats received an intrastriatal graft of embryonic ventral mesencephalic neurons (200,000 cells in young adult rats, 400,000 cells in middle-aged rats; E14 wild-type donors) or a sham graft. LID were evaluated for 9-10 weeks post-engraftment, and GID were assessed 24-48 hr prior to sacrifice. In young adult graft recipients, this research demonstrates that: 1) Met/Met rats display enhanced graft efficacy and paradoxically enriched graft-derived neurite outgrowth compared to Val/Val rats, and 2) the Met allele is strongly linked to GID development and this behavioral phenotype is correlated with neurochemical signatures of glutamatergic neurotransmission by grafted DA neurons. In middle-aged graft recipients, this research indicates that: 1) behavioral enhancement associated with the Met allele is maintained with advancing age, and 2) advanced age is associated with the induction of GID in rats of both genotypes despite the presence of widespread intrastriatal grafts. In this rapidly evolving era of precision medicine, understanding mechanisms underlying the beneficial versus detrimental impact of the Val66Met polymorphism, and/or its interaction with aging, will aid in the development of safe and optimized therapeutic approaches for remodeling the parkinsonian striatum.
Show less

Title: The role of parkin in the recovery of central dopamine neurons from acute neurotoxicant exposure
Creator: Benskey, Matthew John
Date: 2013
Collection: Electronic Theses & Dissertations
Description: Parkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to...
Show moreParkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to identify early molecular events that underlie TIDA neuron recovery from toxicant exposure and adapt these mechanisms in an attempt to rescue NSDA neurons from toxicity. NSDA neurons show loss of axon terminal DA concentrations following acute (20mg/kg; s.c.) and chronic (10 x 20mg/kg; s.c. over 35 days) MPTP administration and exhibit cell death following chronic MPTP administration. In contrast, TIDA neurons show no loss of axon terminal DA concentrations or cell death following acute or chronic MPTP exposure. The recovery of TIDA neurons is independent of extrinsic factors such as decreased toxicant exposure or hormonal activation. TIDA neuron recovery is associated with an increase in the PD-associated proteins, parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1) within the arcuate nucleus (ARC) 24 h following MPTP. Additionally, parkin protein concentrations remain elevated in the ARC for up to 22 days following chronic MPTP administration. In contrast, the susceptibility of NSDA neurons is associated with decreased expression of both parkin and UCH-L1. The high correlation between the presence of the parkin protein and the recovery of DA neurons from MPTP toxicity is consistent with a role of parkin in DA neuron survival. In order to determine if parkin is necessary and sufficient in the recovery of TIDA neurons following MPTP, recombinant adeno-associated viral (rAAV) vectors containing parkin shRNA or a scrambled shRNA were created. Mice received stereotaxic ARC injections of rAAV containing either parkin shRNA or scrambled shRNA (250nl/side; 3.5x1013vg/ml), or remained naïve to surgery, and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four h post-MPTP, TIDA neurons were able to recover axon terminal DA concentrations following MPTP in control and scrambled shRNA treated animals. However, axon terminal DA was significantly reduced 24 hr following MPTP exposure following knockdown of parkin in TIDA neurons. To determine if parkin overexpression would protect NSDA neurons from MPTP toxicity, mice received unilateral stereotaxic injection of rAAV containing parkin into the substantia nigra (SN) (500nl; 3.4x1013vg/ml) and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four hours post-MPTP, parkin overexpression was unable to rescue MPTP-induced loss of DA in the striatum (ST), but did rescue MPTP-induced loss of tyrosine hydroxylase (TH) in the SN and ST. These findings are consistent with the following conclusions: 1) TIDA neuronal recovery from acute MPTP exposure is independent of extrinsic factors and is mediated by an intrinsic ability to increase expression of neuroprotective proteins, 2) The ability of TIDA neurons to up-regulate parkin is at least partially responsible for recovery of axon terminal DA following MPTP, 3) toxicant-induced loss of parkin contributes to MPTP toxicity within NSDA neurons.
Show less

MSU Libraries

Digital Repository

Enabled Filters

Pages

Pages

MSU Libraries

Digital Repository

You are here

Search results

Pages

Pages