Medicine and Health Sciences Commons^™

The Dynamics Of Adult Neurogenesis In Human Hippocampus, Amadi O. Ihunwo, Lackson H. Tembo, Charles Dzamalala

Brain and Mind Institute

The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved In Immunity And Neurogenesis In Simian Immunodeficiency Virus-Infected Macaques, John K Maxi, Matt Dean, Jovanny Zabaleta, Krzysztof Reiss, Gregory J. Bagby, Steve Nelson, Peter J. Winsauer, Francesca Peruzzi, Patricia E. Molina

School of Graduate Studies Faculty Publications

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13-14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Repeated Closed Head Injury In Mice Results In Sustained Motor And Memory Deficits And Chronic Cellular Changes, Amanda Nicholle Bolton Hall, Binoy Joseph, Jennifer M. Brelsfoard, Kathryn E. Saatman

Spinal Cord and Brain Injury Research Center Faculty Publications

Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at …

Glun2b Protein Deficits In The Left, But Not The Right, Hippocampus In Schizophrenia, Amy Geddes, Xu-Feng Huang, Kelly Newell

Xu-Feng Huang

Background Increasing evidence indicates that alterations to the function and subunit composition of the glutamatergic NMDA receptor are associated with the pathophysiology of schizophrenia. The GluN2B protein is a structural and functional subunit of the NMDA receptor, with a growing body of evidence indicating it plays a critical role in cognitive functions mediated by the NMDA receptor. The hippocampus plays a key role in cognitive function, with studies suggesting lateralised glutamatergic dysfunction in this region may contribute to the cognitive deficits observed in schizophrenia patients. The present study, for the first time, investigated GluN2B protein and binding density in the …

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …

Changes In The Adult Glun2b Associated Proteome Following Adolescent Intermittent Ethanol Exposure, H. Scott Swartzwelder, Mary-Louise Risher, Kelsey M. Miller, Roger J. Colban, Danner G. Winder, Tiffany A. Wills

Biomedical Sciences

Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Differential Involvement Of Hippocampal Angiotensin 1 Receptors In Learning And Memory Processes In Bulbectomized Rats, Roman Tashev, Margarita Ivanova, Stiliana Belcheva, Iren Belcheva

Journal of Mind and Medical Sciences

There is conflicting evidence regarding the effect of AT1 receptor antagonists on learning and memory processes. The effects of angiotensin II and losartan administration into CA1 hippocampal area on the avoidance performance in olfactory bulbectomized (OBX) rats using active avoidance (shuttle box) test and passive avoidance (step through) test were investigated. Rats were microinjected unilaterally through implanted guide cannulas into the CA1 area of the dorsal hippocampus and the drugs were administered separately, 5 minutes before each training session. The microinjections of losartan into the left, but not the right CA1 hippocampal area improved the acquisition and retention of active …

In Vivo Mri Signatures Of Hippocampal Subfield Pathology In Intractable Epilepsy., Maged Goubran, Boris C Bernhardt, Diego Cantor-Rivera, Jonathan C Lau, Charlotte Blinston, Robert R Hammond, Sandrine De Ribaupierre, Jorge G Burneo, Seyed M Mirsattari, David A Steven, Andrew G Parrent, Andrea Bernasconi, Neda Bernasconi, Terry M Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo.

EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively …

The Representational-Hierarchical View Of Pattern Separation: Not Just Hippocampus, Not Just Space, Not Just Memory?, B. A. Kent, M. Hvoslef-Eide, L. M. Saksida, T. J. Bussey

Brain and Mind Institute Researchers' Publications

Pattern separation (PS) has been defined as a process of reducing overlap between similar input patterns to minimize interference amongst stored representations. The present article describes this putative PS process from the "representational-hierarchical" perspective (R-H), which uses a hierarchical continuum instead of a cognitive modular processing framework to describe the organization of the ventral visual perirhinal-hippocampal processing stream. Instead of trying to map psychological constructs onto anatomical modules in the brain, the R-H model suggests that the function of brain regions depends upon what representations they contain. We begin by discussing a main principle of the R-H framework, the resolution …

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …

Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh

Marshall Journal of Medicine

Given the difficulty of surgical resection of brain neoplasms located adjacent to vital structures of the brain as well as the challenges posed by the blood-brain-barrier for the efficacy of chemotherapeutic agents, whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are often turned to for patients with brain metastases as well as primary brain neoplasms. Though radiation therapy may be successful in local control of these tumors, many patients experience treatment-related neurocognitive issues later in life. In this review, we examine cognitive dysfunction in brain tumor patients following radiation therapy, with an emphasis on the pediatric population. Articles were …

Sex Differences In Hiv Effects On Visual Memory Among Substance-Dependent Individuals, Michael K. Keutmann, Raul Gonzalez, Pauline M. Maki, Leah H. Rubin, Jasmin Vassileva, Eileen M. Martin

Psychiatry Publications

HIV’s effects on episodic memory have not been compared systematically between male and female substance-dependent individuals. We administered the Brief Visuospatial Memory Test–Revised (BVMT–R) to 280 substance-dependent HIV+ and HIV– men and women. Groups were comparable on demographic, substance use, and comorbid characteristics. There were no significant main effects of sex or HIV serostatus on BVMT–R performance, but HIV+ women performed significantly more poorly on delayed recall. This effect was most prominent among cocaine-dependent HIV+ women. Our findings are consistent with recent speculation that memory impairment may be more common among HIV+ women, particularly those with a history of cocaine …

Context-Dependent Egr1 Expression In The Avian Hippocampus., Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone

Brain and Mind Institute Researchers' Publications

In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.

Microglia And Neurons In The Hippocampus Of Migratory Sandpipers., C G Diniz, N G M Magalhães, A A Sousa, C Santos Filho, D G Diniz, C M Lima, M A Oliveira, D C Paulo, P D C Pereira, D F Sherry, C W Picanço-Diniz

Brain and Mind Institute Researchers' Publications

The semipalmated sandpiper Calidris pusilla and the spotted sandpiper Actitis macularia are long- and short-distance migrants, respectively. C. pusilla breeds in the sub-arctic and mid-arctic tundra of Canada and Alaska and winters on the north and east coasts of South America. A. macularia breeds in a broad distribution across most of North America from the treeline to the southern United States. It winters in the southern United States, and Central and South America. The autumn migration route of C. pusilla includes a non-stop flight over the Atlantic Ocean, whereas autumn route of A. macularia is largely over land. Because of …

From Squirrels To Cognitive Behavioral Therapy (Cbt): The Modulation Of The Hippocampus, Rachel Ariella Bartfeld

The Science Journal of the Lander College of Arts and Sciences

The legitimacy of psychotherapy can often be thrown into doubt as its mechanisms of action are generally considered hazy and unquantifiable. One way to support the effectiveness of therapy would be to demonstrate the physical effects that this treatment option can have on the brain, just like psychotropic medications that physically alter the brain’s construction leaving no doubt as to the potency of their effects. Beginning with the understanding of therapy as a behavior, this paper first questions the possibility of behavior effecting measurable change on the brain. Examining diverse samples of both animals and humans repeatedly shows that the …

An Analysis Of Virtual Place Learning/Navigation In Children And Young Adults Prenatally Exposed To Alcohol, Neil Christopher Dodge

Wayne State University Dissertations

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze …

Identification Of The Effects Of Diabetes Mellitus On The Brain, Tryphina A. Mikhail

Honors Undergraduate Theses

As more studies accumulate on the impact of diabetes mellitus on the central nervous system, they resound with the same conclusion - diabetes has a detrimental effect on cognition regardless of the presence of comorbidities. Less consistent however, are the specific mental processes wherein these declines are noticeable, and the structural changes that accompany these reductions in mental capacity. From global atrophy to changes in the volume of gray and white matter, to conflicting results regarding the effects of hypo- and hyperglycemic states on the development of the hippocampus, the studies display a variety of results. The goal of this …

The Identification Of The Direct And Indirect Pathways Through Which Leptin Facilitates Synaptic Plasticity In The Hippocampus, Catherine Van Doorn

Theses and Dissertations

Leptin, a peptide synthesized by adipocytes in the periphery, has been shown to play significant roles in feeding and energy expenditure mediated by the hypothalamus. Growing evidence supports the role of leptin in influencing synaptic plasticity in the hippocampus in that leptin dose-dependently enhances LTP, alters morphology and neurogenesis, facilitates spatial learning and memory, as well as memory retention. Models of leptin deficiency and resistance have further supported the importance of leptin in synaptic plasticity by exhibiting deficits in electrophysiological, morphological and behavioral tests that are improved after leptin restoration. The effects of leptin when applied directly into the hippocampus …

Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover

All ETDs from UAB

Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …

1h-Magnetic Resonance Spectroscopy In First Episode And Chronic Schizophrenia Patients, Duygu Kirtaş, Ruki̇ye Fi̇li̇z Karadağ, Meli̇ke Ceyhan Balci Şengül, Yilmaz Kiroğlu

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to compare metabolite levels of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate gyrus (ACG), thalamus, and hippocampus in patients with chronic schizophrenia (CSPs) and first psychotic episode patients (FEPs) by the use of magnetic resonance spectroscopy (MRS). Materials and methods: Thirty CSPs, 20 FEPs, and 30 healthy subjects participated in this study. N-Acetylaspartate (NAA), creatine, choline (Cho), and myoinositol levels of the DLPFC, ACG, thalamus, and hippocampus were measured by 1H-MRS. Results: It was determined that the NAA/Cho ratio was lower in both the FEPs and CSPs than the healthy controls in the …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Neuroinflammatory Pain Models In Mice, Muzaffar Abbas

Electronic Theses and Dissertations

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary …

Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy

All ETDs from UAB

Understanding biological mechanisms that shape brain development and susceptibility to emotional dysfunction is crucial for generating improved treatments for depression and anxiety disorders. To study neurodevelopmental factors that influence emotionality, we use model rats that were bred for distinct behavioral responses to novelty. Rats bred for low novelty response (LRs) exhibit a high anxiety-/depressive-like phenotype compared to high novelty responder rats (HRs), which vigorously explore novelty and exhibit high impulsivity, aggression, and risk-taking. Transcriptome profiling revealed multiple gene expression differences in the early postnatal hippocampus and amygdala and in the adult amygdala of HR/LR rats. Through gene ontology analysis, we …