Medical Neurobiology Commons^™

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

The Effects Of Astrocytic Derived Insulin-Like Growth Factor (Igf-1) On Cognition And Astrocytes, Destiny Wilson

Honors Theses

Insulin-like growth factor 1 (IGF-1) is a neuroendocrine signaling hormone that plays a vital role in growth and development, as well as learning and memory. Inhibition of this hormone results in cognitive impairments like those seen with age-related decline. While a majority of research has focused on the role of IGF-1 on neurons, the role of astrocytes still needs to be explored. Our research investigates how astrocytes and cognition are affected as a result of direct regulation of localized IGF-1 production in early development and after puberty. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary …

The Role Of Corticothalamic Projections (Prelimbic Cortex To Nucleus Reuniens) In Working Memory, Phillip Kumpf, Paul C. Kumpf, S. D. Dunn, Evan Ciacciarelli, T. Gohar, Timothy Sloand, Mark Niedringhaus, Elizabeth West

Rowan-Virtua Research Day

Working memory (WM) is the ability to store information for short periods of time and is used to execute tasks

WM has been understood to work via the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC), but they do not directly project to each other

The nucleus reuniens of the thalamus (Re) is a “middle man” between the mPFC and dHPC

There are projections between the prelimbic cortex (PrL) and Re that may be used during WM

To test the connection of the PrL to Re, a delayed nonmatch to position (DNMTP) task was performed

Neuronal Activity Within The Ventral Tegmental Area Is Correlated With Cocaine-Seeking Behavior In Male, But Not Female, Rats, Colton D. Spencer, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

The objective of this study was to begin to determine the neurobiological underpinnings of psychosocial stress-induced cocaine seeking. Social defeat stress, achieved using the well-established resident-intruder procedure, is an ecologically-valid psychosocial stressor in rodents that may more closely recapitulate those psychosocial experiences that elicit cocaine craving and relapse in human cocaine users. Our laboratory has developed a model of psychosocial stress-induced relapse in rats in which extinguished cocaine seeking is reinstated by re-exposure to a discrete cue that signals impending social defeat stress. We previously reported that an individual rat’s predilection towards the display of active coping behaviors during prior …

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.

The Brodmann Area 39/40 Of The Brain In Alzheimer’S, Mild Cognitive Impairment, And No Cognitive Impairment Subjects At Advanced Age Demonstrate Comparable Levels Of Blood-Brain Barrier Breach, Dhara Rana, Forum Mangrola, Randel L. Swanson, Venkat Venkataraman, David A. Bennett, Zoe Arvanitakis, David Libon, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

• Alzheimer’s disease (AD) is one of the most common form of dementia

• Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD

• Pathogenesis Theories:

• o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein
• o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis

• Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing

• Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subjects

Plasmalogen Deficiency: A Risk Factor For Dementias And Potential Treatment Target, Mitchel A. Kling, Mallika Mendu, Rima F. Kaddurah-Daouk, Sheldon Jordan, Dayan B. Goodenowe

Rowan-Virtua Research Day

Altered lipid metabolism is implicated in the risk of sporadic Alzheimer’s disease (AD) and related dementias (ADRD); however, the precise mechanisms accounting for findings from observational studies remains to be fully elucidated.

Plasmalogens are a subclass of integral membrane phospholipids with unique properties that appear to play important roles relevant to the pathophysiology of AD and ADRD, including vesicle fusion necessary for synaptic neurotransmitter release, modulation of membrane fluidity and microdomain dynamics, membrane antioxidant functions, and neuroprotection. Like the more familiar phosphatides, plasmalogens are synthesized on a 3-carbon glycerol backbone; however, they differ from phosphatides by the presence of a …

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 …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

The Impact Of Volume Of Tissue Activation On Cortical-Striatal Networks And Verbal Fluency Declines In Post-Deep Brain Stimulation Parkinson's Disease Patients., Alexander Luke Alley

Electronic Theses and Dissertations

This study investigated the cortical-striatal networks of verbal fluency declines in 6-month, post-operative, deep brain stimulation Parkinson’s Disease patients. Nine Parkinson’s disease participants with implanted STN or GPi DBS systems were recruited for this study. Verbal fluency data was obtained from each patient preoperatively and 6- months post implantation. The stimulation-based volume of tissue activated area (VTA) of each target site (STN or GPi) was analyzed using Lead-DBS and Lead-Group. The white matter tracks intersecting each patient’s VTA, terminating in the pre-SMA, SMA, caudate nucleus, and anterior cingulate were investigated and correlated with verbal fluency declines. We found statistically significant …

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …

The Effects Of Executive Function Between Anxiety And Math Achievement In Adolescents, Mckenzie Hall

UNLV Theses, Dissertations, Professional Papers, and Capstones

Anxiety in Children can develop into pervasive disorders in adulthood if not treated. Research shows dysfunctional Executive Function (EF) and anxiety are both shown to have a negative impact on math achievement in children and adolescents (Trezise & Reeve, 2018; Kalaycioglu, 2015; Owens, Stevenson, Hadwin & Norgate, 2012). Chung, Weyandt, and Swentosky (2014) found biological and neuropsychological support for EF as a unitary and multifaceted processor for regulating our emotional states as well as our daily procedures. Anderson’s (2002) model of Executive Control System (ECS) allows the factors of EF to be examined using a developmental approach towards EF processes. …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

The Relationship Between Pro-Stress And Anti-Stress Receptors In The Stress-Learning Brain Regions Of Female Mice, Nathan Popp

Honors Thesis

Human men and women react to stress in different ways, both biologically and psychologically (Verma et al., 2011). Orexins (or hypocretins) are neuropeptides involved in eliciting a stress response and have been shown to have opposing actions via two different receptors. Activation of the Orx1 receptor promotes stress, while activation of the Orx2 receptor relieves stress (Staton et al., 2018). Using the Stress Alternatives Model (a four-day paradigm in which small female mice are in an open arena with a larger aggressor mouse), distinct phenotypic behaviors can be observed after the second day: anxiety-prone and stress-resilient. After the second day, …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Actl6a Coordinates Axonal Caliber Recognition And Myelination In The Peripheral Nerve, Hye-Jin Park, Eric Tsai, Dennis Huang, Michael Weaver, Luciana Frick, Ace Alcantara, John J. Moran, Julia Patzig, Carmen V. Melendez-Vasquez, Gerald R. Crabtree, M.L. Feltri, John Svaren, Patricia Casaccia

Advanced Science Research Center

Cells elaborate transcriptional programs in response to external signals. In the peripheral nerves, Schwann cells (SC) sort axons of given caliber and start the process of wrapping their membrane around them. We identify Actin-like protein 6a (ACTL6a), part of SWI/SNF chromatin remodeling complex, as critical for the integration of axonal caliber recognition with the transcriptional program of myelination. Nuclear levels of ACTL6A in SC are increased by contact with large caliber axons or nanofibers, and result in the eviction of repressive histone marks to facilitate myelination. Without Actl6a the SC are unable to coordinate caliber recognition and myelin production. Peripheral …

Acute Oxygen-Sensing Via Mitochondria-Generated Temperature Transients In Rat Carotid Body Type I Cells, Ryan J. Rakoczy, Clay M. Schiebrel, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = …

The Parkinson's Wellness Project: An 8-Part Educational Video Series, Samantha L. Stevenson

OTD Capstone Projects

The Parkinson’s Wellness Project is an 8-part educational video series created by Samantha Stevenson, a student in Belmont University’s Doctorate Program in Occupational Therapy. Purpose: This project was created to benefit all persons with Parkinson’s disease (PD) and their care partners who attend Rocksteady Boxing (RSB) in Franklin/Nashville, TN. Methodology: The student conducted research to identify the salient issues experienced by people living with PD. The issues were then synthesized into 8 separate categories including the following: facial expression, mental health, sexual health, self-care, sleep, diet and nutrition, meditation, and postural alignment. Experts in the healthcare field produced specialized content …

Sex Differences In Hippocampal O-Glcnacylation Of The Adult Mouse Brain, Makenzie Johnson

Selected Honors Theses

The hippocampus is a structure in the brain crucial for learning and memory. This occurs by synaptic remodeling known as long term potentiation and long term depression. Modifications of proteins in the hippocampus can affect its function. One of these modifications is the addition of O-linked β-N-acetylglucosamine, also known as O-GlcNAc. This is a sugar produced from glucose by the hexosamine biosynthetic pathway that is reversibly added onto serine and threonine residues of proteins by O-GlcNAc Transferase, or OGT. It is reversibly removed from these residues by O-GlcNAcAse, or OGA. This modification has been implicated in diabetes, cardiac dysfunction, and …

Applications And Challenges Of Neural Stem Cell Therapy, John Brewster

Senior Honors Theses

In response to the many neurological disorders that plague humanity, no treatment shows more promise than stem cell therapy. By using these special cells to regrow damaged neurons and combat sources of disease in affected patients, researchers hope to treat neurological disorders of all kinds. While great strides have been made in laboratory settings, the widespread use of stem cells to treat neurological disorders in humans is still a distant goal. Recent advancements have been made in the area of neural stem cell therapy, but complications arise when using this method to treat neurological disorders.

Oleic Acid Is An Endogenous Ligand Of Tlx/Nr2e1 That Triggers Hippocampal Neurogenesis, Prasanna Kandel, Fatih Semerci, Rachana Mishra, William Choi, Aleksandar Bajic, Dodge Baluya, Lihua Ma, Kevin Chen, Austin C Cao, Tipwarin Phongmekhin, Nick Matinyan, Alba Jiménez-Panizo, Srinivas Chamakuri, Idris O Raji, Lyra Chang, Pablo Fuentes-Prior, Kevin R Mackenzie, Caroline L Benn, Eva Estébanez-Perpiñá, Koen Venken, David D Moore, Damian W Young, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated …

The Anti-Inflammatory Agent Bindarit Attenuates The Impairment Of Neural Development Through Suppression Of Microglial Activation In A Neonatal Hydrocephalus Mouse Model, Eri Iwasawa, Farrah N. Brown, Crystal Shula, Fatima Kahn, Sang Hoon Lee, Temugin Berta, David R. Ladle, Kenneth Campbell, Francesco T. Mangano, June Goto

Neuroscience, Cell Biology & Physiology Faculty Publications

Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy …

Evaluation Of Hippocampal Allostatic Load-Associated Factors In Animal Models Of Post-Traumatic Stress Disorder: Relevance To Human Ptsd, Dennis Parker Kelley

LSU Doctoral Dissertations

Post-traumatic stress disorder (PTSD) is associated with elevated allostatic load, nearly double the risk for metabolic syndrome, reduced hippocampal volume, and contextual memory processing deficits. Emerging evidence suggests that these stress effects may predispose individuals to the development of PTSD, and there is a known relationship between chronic stress and metabolic dysfunction. In this work, we utilized two rat models of PTSD to explore these connections. We used an acute predator odor stressor to investigate the relationship between PTSD-like behaviors and mitochondrial dysfunction in the hippocampus of rats, and we observed that conditioned place avoidance was associated with reduced mitochondrial …

Laser Interstitial Thermal Therapy For Posterior Fossa Lesions: A Systematic Review And Analysis Of Multi-Institutional Outcomes, Mohammadmahdi Sabahi, Stephen J. Bordes, Edinson Najera, Alireza M. Mohammadi, Gene H. Barnett, Badih Adada, Hamid Borghei-Razavi

School of Medicine Faculty Publications

Background: Laser interstitial thermal therapy (LITT) has emerged as a treatment option for deep-seated primary and metastatic brain lesions; however, hardly any data exist regarding LITT for lesions of the posterior fossa. Methods: A quantitative systematic review was performed. Article selection was performed by searching MEDLINE (using PubMed), Scopus, and Cochrane electronic bibliographic databases. Inclusion criteria were studies assessing LITT on posterior fossa tumors. Results: 16 studies comprising 150 patients (76.1% female) with a mean age of 56.47 years between 2014 and 2021 were systematically reviewed for treatment outcomes and efficacy. Morbidity and mortality data could be extracted for 131 …

Childhood Trauma And Chronic Disease, Breanna Urena

Graduate Research Projects

No abstract provided.

A Systematic Review And Meta-Analysis Of The Relationship Between The Creb Protein's Neuroplastic Functions And The Implications In Neurodegenerative Diseases: A Possible Link Between Synaptic Plasticity And Neurodegenerative Diseases, Mani Sarmast

Honors Undergraduate Theses

In this two-part study, I investigated whether the cyclic-adenosine monophosphate response element-binding (CREB) protein has the potential to be clinically modulated as a therapeutic target for the treatment of neurodegenerative diseases. Part one consisted of a systematic review that was conducted on select articles gathered through a stepwise method to explore (1) the relationship between diseased, neurodegenerative brains and levels of active, phosphorylated CREB (pCREB), (2) increased activation of CREB as a treatment for neurodegenerative symptoms, and (3) a potential therapeutic drug for neurodegenerative diseases that can target CREB signaling. The results of the systematic review showed evidence that suggested …

Stereotactic Radiosurgery For Pituitary Adenomas: A Review Of Literature, Kaynat Siddiqui, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.

More Than Just Statics: Static And Temporal Dynamic Changes In Intrinsic Brain Activity In Unilateral Temporal Lobe Epilepsy, Chengru Song, Xiaonan Zhang, Shaoqiang Han, Keran Ma, Kefan Wang, Xinyue Mao, Yajun Lian, Xianchang Zhang, Jinxia Zhu, Yong Zhang, Jingliang Cheng

Faculty, Staff and Student Publications

BACKGROUND: Temporal lobe epilepsy (TLE) is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.

OBJECTIVE: This study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.

METHODS: Six static intrinsic brain activity (IBA) indicators [amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), global signal correlation (GSCorr), and voxel-mirrored homotopic connectivity (VMHC)] and their corresponding dynamic indicators, such as dynamic ALFF (dALFF), dynamic fALFF …

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …