Molecular and Cellular Neuroscience Commons^™

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

Novel Antiviral Effect Of A Small Molecule Onc201 And Its Potential Application In Hiv-1 Eradication, Runze Zhao

Theses & Dissertations

Despite the success of antiretroviral therapy (ART), eradication of HIV-1 from brain reservoirs remains elusive. HIV-1 brain reservoirs include perivascular macrophages that are behind the blood-brain barrier and difficult to access by ART. Macrophages express transcription factor FOXO3a and the TNF superfamily cytokine TRAIL, which are known to target HIV-1-infected macrophages for viral suppression. ONC201 is a novel and potent FOXO3a activator capable of inducing TRAIL. It can cross the blood-brain barrier, and has shown an antitumor effect in clinical trials. We hypothesized that activation of FOXO3a/TRAIL by ONC201 will reduce the size of HIV-1 brain reservoirs. Using primary human …

Mechanisms Of Calcium-Dependent Neurotransmission In Photoreceptors, Justin J. Grassmeyer

Theses & Dissertations

Rod and cone photoreceptors initiate vision by transforming light into graded membrane voltage changes that in turn dictate the rate of continuous Ca²⁺-dependent neurotransmission to postsynaptic neurons. Continuous release relies on synaptic ribbons at photoreceptor active zones, which organize exocytotic proteins and deliver vesicles to release sites near voltage-gated Ca²⁺ channels. Individual cones possess multiple ribbon synapses at which they contact postsynaptic neurons. We examined heterogeneity in signaling at individual ribbon synapses in salamander cones by measuring the voltage dependence of Ca²⁺ currents (I_Ca) and Ca²⁺ influx at individual ribbon release sites. Ca …