Life Sciences Commons^™

A Preliminary Report: The Hippocampus And Surrounding Temporal Cortex Of Patients With Schizophrenia Have Impaired Blood-Brain Barrier, Eric L. Goldwaser, Randel L. Swanson, Edgardo J. Arroyo, Venkat Venkataraman, Mary C. Kosciuk, Robert G. Nagele, L. Elliot Hong, Nimish K. Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB.

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …

Effect Of Uracil Dna Glycosylase Activity On The Efficacy Of Thymidylate Synthase Inhibitor/Hdac Inhibitor Combination Therapies In Colon Cancer, Rashmi Kulkarni, Brian P Weiser

Rowan-Virtua Research Day

Human uracil DNA glycosylase (UNG2) is responsible for removing uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5-fluorouracil, fluorodeoxyuridine, and pemetrexed) and we determined that, except for 5-fluorouracil, all other TS inhibitors were significantly more potent in UNG2 KO cells compared to wild-type HT29 cells. Interestingly, UNG2 protein levels …

Cyclin C Is Sufficient For Myoblast Differentiation-Induced Mitochondrial Fragmentation, Alicia N. Campbell, Randy Strich

Rowan-Virtua Research Day

One of the largest and most dynamic tissues in the body, skeletal muscle, requires constant regeneration and upkeep. Dysregulation of this regeneration process has been implicated in many neuromuscular diseases and myotonic dystrophies. Regeneration requires the differentiation of myogenic lineages including exiting the cell cycle, gene expression changes, and fusing of myoblasts into multinucleate myotubes. Part of this reconstruction requires the breakdown and repopulation of mitochondrial networks. At the early onset of myoblast differentiation, there is an upregulation of dynamin-related protein, Drp1, and an increase in mitophagy mediated by sequestosome (SQSTM1) removal of mitochondria.

Previously, our lab has shown that …

Interaction Of Fluorescent Probes With Sirtuin Proteins, James Fusco, Brian P Weiser

Rowan-Virtua Research Day

Sirtuins are a class of proteins belonging to the Sir2 (Silencing information regulator 2) family of NAD+ dependent protein lysine deacylases. Different Isoforms (SIRT1-SIRT7) differ in their specific deacylase activity and cellular location. They have roles in DNA repair, glucose metabolism, and cellular proliferation which make them highly desirable targets for carcinoma therapeutics. We previously used 1-aminoanthracene’s (AMA) fluorescent properties when bound with SIRT2 (Kd of 37 μM) to develop a high-throughput screen to identify novel ligands that inhibit SIRT2’s enzymatic activities. We hope to reveal other potential probes for future high-throughput screening with all the sirtuin isotopes. 1-AMA’s fluorescence …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

Opioids exert their abuse-related effects by enhancing dopamine (DA) neurotransmission within the brain’s mesolimbic reward system, a neural projection involving DA neurons in the ventral tegmental area (VTA) that project to medium spiny neurons within the nucleus accumbens (NAc). Mu (MOR) are expressed by several populations of GABAergic neurons that tonically inhibit VTA DA neurons. By inhibiting these GABAergic neurons in a MOR-dependent manner, opioids indirectly enhance DA neurotransmission via disinhibition of DAergic neurons. Accumulating evidence indicates that selective pharmacological antagonism of the dopamine D3 receptor (D3R) attenuates the abuse-related effects of several opioids, but the neurobiological mechanisms mediating this …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …