Doctor of Philosophy (Ph.D.), Bowling Green State University, 2022, Psychology

Addiction disorders, majorly governed by the mesolimbic dopamine system, constitute a global health crisis, with alcoholism being particularly prevalent and pernicious. Alterations of the gut microbiome correlate with alterations in addiction pathologies, both physiological and behavioral. Fecal Microbial Transfer is an established research and clinical technique for manipulating the Brain-Gut-Microbiome Axis in many conditions. Ethanol is known to have massive impacts on both the gut and dopamine systems, potentially producing impacts on the latter via some action on the former. The Alcohol Preferring and Non-Preferring rat models are well suited for investigating neuropsychological processes related to alcohol addiction. We performed FMT between P and NP rats during chronic ethanol exposure to investigate the effect on drinking behaviors, and then we examined the expression of dopamine receptors 1 (D1R) and 2 (D2R) in three brain regions related to addiction (hippocampus, prefrontal cortex, and nucleus accumbens). We found that NP rats drank and preferred alcohol significantly less than P rats before, during, and after the FMT treatment during chronic ethanol exposure. Differences in drinking behaviors were not statistically significant between weeks, though there were slight patterns of a bi-directional influence, with P rats decreasing and NP rats increasing drinking during FMT. Levels of the two receptor types correlated positively with each other in each brain region. D1R in hippocampus and nucleus accumbens correlated positively with preference for the weaker concentration of ethanol, and both D1R and D2R correlated positively with intake of the stronger concentration after the FMT treatment. We also found that in P rats, FMT reduced alpha diversity of the gut microbiome, and reduced abundance of Akkermancia municiphila, and Bifidobacterium animalis; these gut conditions are associated with healthier outcomes, which may suggest that FMT impacted drinking beha (open full item for complete abstract)

Committee: Howard Casey Cromwell Ph.D. (Committee Chair); Verner Bingman Ph.D. (Committee Member); Sherri Horner Ph.D. (Other); Michael Zickar Ph.D. (Committee Member); Daniel Weigmann Ph.D. (Committee Member) Subjects: Neurosciences; Psychology

Doctor of Philosophy, Case Western Reserve University, 1991, Pharmacology

Previous studies have suggested that the presence of functional sympathetic cholinergic innervation plays a critical role in regulating both the development and maintenance of rat sweat gland secretory function. Our goals were: (1) determine how muscarinic receptor expression correlated with innervation and function of the sweat glands; (2) determine the nature of the molecular signal intrinsic to the innervation. Using ligand-binding and autoradiographic techniques, we determined that the concentration of muscarinic receptors in sweat gland rich tissue was 301 fmoles/mg protein, the affinity was 131 pM. Further investigation revealed that the sweat gland receptor belongs to the M2 glandular pharmacological subclass and in situ hybridization histochemistry indicated that rat sweat glands express the m3 molecular receptor subtype. Developmental studies revealed that muscarinic ligand binding sites were first detectable on P4; mRNA and receptor concentration attained adult levels by P14, although only small proportion of glands are functional at this age. The pharmacological and molecular properties of muscarinic receptors of adult rats sympathectomized at birth and adult glands acutely denervated were s imilar to control. Examination of the putative second messenger that controls fluid secretion demonstrated that similar levels of IP3 and calcium transients were genertate in control and nonresponsive secretory cells. These results suggest (1) expression of receptors is part of an intrinsic program and (2) the defect in nonresponsive glands lies distal to generation of the calcium transient. To define the molecular signal(s) responsible, we disrupted normal cholinergic transmission in developing postnatal rats and in adult rats by chronically administering atropine. Treatment of young postnatal rats with atropine for 7 days blocked the development of secretory function, and caused the loss of secretory function in adult animals. In addition, treatment with pilocarpine (open full item for complete abstract)

Committee: Story Landis (Advisor) Subjects: Biology, Neuroscience

Master of Arts, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1950, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2006, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1950, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1950, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1946, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1962, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1950, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1961, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1962, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1914, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1950, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science (MS), Wright State University, 2024, Physiology and Neuroscience

Organophosphate pesticides, such as Malathion, are commonly used in U.S. and foreign agricultural industries and homes so exposure is inevitable and unavoidable for some people (example: military personnel). Environmental exposure to organophosphate pesticides is an identified risk of neuropathy and neurodegeneration. This study investigates the morphological changes of muscle spindle mechanoreceptors in rat extensor digitorum longus (EDL) muscles in response to environmental Malathion exposure. Animals were exposed to low-dose Malathion 5 days a week for 4 weeks and muscle tissue was collected within 5 days of the last exposure. The EDL muscle was frozen and sectioned onto slides before immunohistochemistry was performed to identify the muscle spindle sensory neurons in the muscle. To analyze morphological changes confocal images were taken, and three parameters of the muscle spindles were measured: length, inter-rotational distance (IRD), and axonal width (AW). In this experiment, we found no significant differences between the Control/Saline and Malathion/Exposure groups. Expanding this research will help us understand the effects of pesticide exposure, even at low doses.

Committee: David R. Ladle Ph.D. (Advisor); Christopher N. Wyatt Ph.D. (Committee Member); Mark M. Rich M.D., Ph.D. (Committee Member) Subjects: Neurosciences; Physiology

Master of Science in Pharmaceutical Science (MSP), University of Toledo, 2024, Pharmaceutical Sciences (Pharmacology/Toxicology)

Chronic ethanol consumption can lead to an increase in extracellular glutamate concentrations in key reward brain regions, such as medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). These levels increase in the liver as well, consequently leading to oxidative stress and neuroinflammation. Previous studies from our lab tested β-lactam antibiotics and the novel β-lactam non-antibiotic, MC-100093, which showed upregulation in the major astrocytic glutamate transporter, GLT-1, and consequently reduction of ethanol intake and normalization of glutamate homeostasis. The present studies tested the effects of the novel synthetic β-lactam non-antibiotic drug, MC-100093, in chronic ethanol intake and assessing neuroinflammatory and neurotrophic factors in subregions of the mPFC and NAc in male P rats as well as the liver in female P rats. MC-100093 treatment reduced ethanol intake after a 5-week free choice (15% and 30% ethanol, v/v, and water) drinking regimen. Importantly, MC-100093 attenuated ethanol-induced downregulation of brain derived neurotrophic factor (BDNF) expression in these brain regions. In addition, MC- iv 100093 attenuated ethanol-induced upregulation of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-), receptor for advanced glycation end products (RAGE), and high mobility group box 1 (HMGB-1) in these brain regions. Furthermore, MC-100093 treatment attenuated ethanol-induced increase of peroxisome proliferatoractivated receptor alpha (PPAR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor kappa B (NF-κB) in the liver. MC-100093 treatment reduced ethanol intake and this behavioral effect was associated with attenuation of reduced neurotrophic factors and increased pro-inflammatory factors. MC-100093 is considered a small molecule that may have potential therapeutic effects for the treatment of the effects of chronic exposure to ethanol

Committee: Youssef Sari (Committee Chair) Subjects: Pharmacology; Toxicology

Master of Science (MS), Wright State University, 2023, Physiology and Neuroscience

Neurodegenerative diseases such as multiple sclerosis affect millions of people around the globe, and promising treatments to counter its progress have been studied extensively. In our study, we used Dawley rats and tested them using the Montoya Staircase test to evaluate their ability to use their forelimbs. After training, surgery was performed using lysolecithin to induce focal demyelination on the rats. After the surgery a drug combination of fluoxetine, ibuprofen, and ascorbic acid was used on injured rats and they were then retested on the Montoya Staircase test. They were then sacrificed and were stained for doublecortin (DCX) and nuclear factor kappa B (NFkB) to see how the drug combination would affect neurogenesis and remyelination. Our results found that when introduced, the drug combination caused a decrease in the DCX and an increase in the NFkB staining. This suggests that the drug combination would have an impact on the differentiation of oligodendrocytes during recovery since a decrease in DCX would indicate that the DCX is assisting with the proliferation and migration of new oligodendrocytes while an increase in NFkB would infer that as NFkB is being activated more oligodendrocyte progenitor cells are being led to survival.

Committee: Adrian Corbett Ph.D. (Committee Chair); Michael Matott Ph.D. (Committee Member); Christopher Wyatt Ph.D. (Committee Member) Subjects: Neurosciences