Medical Neurobiology Commons^™

Pyrosequencing Analysis Of Irs1 Methylation Levels In Schizophrenia With Tardive Dyskinesia, Yanli Li, Kesheng Wang, Ping Zhang, Junchao Huang, Ying Liu, Zhiren Wang, Yongke Lu, Shuping Tan, Fude Yang, Yunlong Tan

Pharmacology, Physiology and Toxicology

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and …

Regulation Of Synaptic Development By Astrocyte Signaling Factors And Their Emerging Roles In Substance Abuse, Christopher D. Walker, W. Chris Risher, Mary-Louise Risher

Biomedical Sciences

Astrocytes have critical functions throughout the central nervous system (CNS) and have emerged as regulators of synaptic development and function. With their highly complex morphologies, they are able to interact with thousands of synapses via peripheral astrocytic processes (PAPs), ensheathing neuronal axons and dendrites to form the tripartite synapse. In this way, astrocytes engage in crosstalk with neurons to mediate a variety of CNS processes including the regulation of extracellular matrix protein signaling, formation and maintenance of the blood-brain barrier (BBB), axon growth and guidance, homeostasis of the synaptic microenvironment, synaptogenesis, and the promotion of synaptic diversity. In this review, …

Brain Damage Associated With Impaired Sentence Processing In Acute Aphasia, Sigfus Kristinsson, Helga Thors, Grigori Yourganov, Sigridur Magnusdottir, Haukur Hjaltason, Brielle C. Stark, Alexandra Basilakos, Dirk B. Den Ouden, Leo Bonilha, Chris Rorden, Gregory Hickok, Argye E. Hillis, Julius Fridriksson

Communication Sciences and Disorders Faculty Articles and Research

Left-hemisphere brain damage commonly affects patients' abilities to produce and comprehend syntactic structures, a condition typically referred to as “agrammatism.” The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, for example, Broca's area, anterior temporal areas, and temporo-parietal areas. We examined the association between damage to specific language-related ROIs and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca's area, would predict syntactic processing abilities. One hundred four individuals with acute aphasia (< 20 days poststroke) were included in the study. Structural MRI scans were obtained, and all participants completed a 45-item sentence–picture matching task. We performed an ROI-based stepwise regression analyses to examine the relation between cortical brain damage and impaired comprehension of canonical and noncanonical sentences. Damage to the posterior middle temporal gyrus was the strongest predictor for overall task performance and performance on noncanonical sentences. Damage to the angular gyrus was the strongest predictor for performance on canonical sentences, and damage to the posterior superior temporal gyrus predicted noncanonical scores when performance on canonical sentences was included as a cofactor. Overall, our models showed that damage to temporo-parietal and posterior temporal areas was associated with impaired syntactic comprehension. Our results indicate that the temporo-parietal area is crucially implicated in complex syntactic processing, whereas the role of Broca's area may be complementary.

A Phantom Of The Past: Withdrawal From Meprobamate Presenting With Focal Seizures., Thomas M. Zink, John E. Erickson

Journal of Maine Medical Center

Introduction: Meprobamate (Miltown, Equinil) is a sedative-hypnotic medication that first gained popularity as an anxiolytic and later as a muscle relaxant. It is a major metabolite of the more commonly used muscle relaxant carisoprodol (Soma). In vitro and electroencephalogram studies demonstrated that meprobamate modulates gama-aminobutyric acid (GABA) receptors, similar to barbiturates. Withdrawal from meprobamate manifests in symptoms ranging from mild anxiety to severe autonomic instability and death. Meprobamate is rarely prescribed, but is still given to a small subset of elderly patients.

Clinical findings: In this case of meprobamate withdrawal, the patient initially displayed altered mental status and recurrent seizures …

Dynamic Blood-Brain Barrier Regulation In Mild Traumatic Brain Injury, Eoin O'Keeffe, Eoin Kelly, Yuzhe Liu, Chiara Giordano, Eugene Wallace, Mark Hynes, Stephen Tiernan, Aidan Meagher, Chris Greene, Stephanie Hughes, Tom Burke, John Kealy, Niamh Doyle, Alison Hay, Michael Farrell, Gerald A. Grant, Alon Friedman, Ronel Veksler, Michael G. Molloy, James F. Meaney, Niall Pender, David Camarillo, Colin P. Doherty, Matthew Campbell

Articles

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Cerebrospinal Fluid Neurofilament Light Concentration Predicts Brain Atrophy And Cognition In Alzheimer's Disease, Kunal Dhiman, Veer Bala Gupta, Victor L. Villemagne, Dhamidhu Eratne, Petra L. Graham, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Ashley I. Bush, Christopher C. Rowe, Colin L. Masters, David Ames, Eugene Hone, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins

Research outputs 2014 to 2021

Introduction
This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.
Methods
CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).
Results
CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P < .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P< .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.
Discussion
CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

The Efficacy Of Ketamine In Adult Patients With Obsessive Compulsive Disorder With Symptoms Refractory To Standard Of Care Treatment., Brooke Thornton

Capstone Showcase

First line pharmacologic treatments for adult patients with Obsessive Compulsive Disorder (OCD) involve selective serotonin/norepinephrine reuptake inhibitors (SSRI/SNRIs). These drug classes often fail to deliver timely relief of symptoms as well as maintain longevity of symptom recurrence. This research analyzed the use of ketamine in adult patients suffering with OCD for the purposes of more efficacious management of symptoms. Although ketamine demonstrated a timelier relief of symptoms in some small clinical studies, its effects were ultimately unable to be sustained long term. Additionally, a wide range of adverse effects including dissociation, and rebound symptoms were observed. As a result, large …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

Brain Development: Why The Young Sleep Longer, Budhaditya Chowdhury, Orie T. Shafer

Advanced Science Research Center

From absorbing new languages to mastering musical instruments, young children are wired to learn in ways that adults are not (Johnson and Newport, 1989). This ability coincides with periods of intense brain plasticity during which neurons can easily remodel their connections (Hubel and Wiesel, 1970). Many children are also scandalously good sleepers, typically getting several more hours of sleep per night than their parents (Jenni and Carskadon, 2007). As sleep deprivation has negative effects on learning and memory, learning like a child likely requires sleeping like one (Diekelmann and Born, 2010). Yet, how the ability to sleep for longer is …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Characterization Of Sensory And Shelter Enrichment In The Rodent Research Habitat, Amber M. Paul, Yasaman Shirazi-Fard, America Reyes, Moniece Lowe, Margareth Cheng-Campbell, Sungshin Choi, Eduardo Almeida, April Ronca, Ruth K. Globus

Publications

The ISS provides a platform for conducting Rodent Research (RR) in microgravity and 9 missions have been successfully conducted. The results from these experiments have begun to provide new insights into the effects of spaceflight on mammalian physiological systems. After RR-1-4, the Flight IACUC required inclusion of additional cage enrichment into the Rodent Habitats (RH) to “enhance animal well-being by providing animals with sensory and motor stimulation, through structures and resources that facilitate the expression of species typical behaviors”. A Hut, in the form of a rigid, mesh igloo-like shelter was implemented beginning with RR-5. The potential influence of the …

Effects Of Dabigatran In Mouse Models Of Aging And Cerebral Amyloid Angiopathy, Neethu Michael, Mher Mahoney Grigoryan, Kelley Kilday, Rachita K. Sumbria, Vitaly Vasilevko, Joanne Van Ryn, David H. Cribbs, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) …

Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injury (PNI) is an excellent model for studying neural responses to injury and elucidating the mechanisms that can facilitate axon regeneration. As such, several animal models have been employed to study regenerative mechanisms after PNI, including Aplysia, zebrafish, rabbits, cats and rodents. This protocol describes how to perform a sciatic nerve injury and repair in mice, one of the most frequently used models to study mechanisms that facilitate recovery after PNI, and that takes advantage of the availability of many genetic models. In this protocol, we describe a method for using fibrin glue to secure the proximal …

Influence Of Social Isolation During Prolonged Simulated Weightlessness By Hindlimb Unloading, Candice G.T. Tahimic, Amber M. Paul, Ann-Sofie Schreurs, Samantha M. Torres, Linda Rubinstein, Sonette Steczina

Publications

The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation …

Cannabidiol Is Beneficial In Management Of Drug-Resistant Dravet Syndrome, Nikita Desai

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Devinsky O, Cross H, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.

Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sleep is a highly regulated homeostatic process that is disrupted in an estimated 50-70 million Americans. Regulation of sleep depends upon coordinated signaling of multiple neurotransmitter systems. In particular, inhibitory gamma-aminobutyric acid (GABA) signaling is required to suppress wake-active brain regions in order to initiate and maintain sleep states. GABA type A receptors (GABAARs) are ionotropic receptors with subunit compositions uniquely enriched on subcellular domains of target cells. α2 subunit-containing GABAARs are the primary target of GABA released onto the axon initial segment (AIS), a site critical for phasing the oscillatory activity of cortical cells. α2-containing GABAARs have previously been …

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

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson

Neuroscience, Cell Biology & Physiology Faculty Publications

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed …