Medicine and Health Sciences Commons^™

Histological And Immunohistochemical Observations Of The Hippocampus In Clinically Established Neurodegenerative Disorders Linked To Cause Of Death, Joshua Owolabi, Jacquelyn Gerhart, Rasheed Agboola, Steven Morency, Brian J. Balin Phd

Research Day

Introduction: Neurodegeneration remains a very important subject of neuroscience research. While experimental studies have modeled conditions and attempted to provide insights, special opportunities exist in situations where clinically established conditions in the actual human brain can be investigated for the neurological, glial and molecular changes that characterize brain changes that produce pathological and neuronal aberrations that are manifested in these conditions. This study considers hippocampi in brains that have suffered clinically established neurodegeneration leading to death.

Methods: Twelve hippocampus samples [N=12] were obtained from 6 brains with clinically established cause of death being neurodegenerative disorders. In each case, whole hippocampi …

How Does Schizophrenia Affect The Expression Of Alpha 7 Nicotinic Acetylcholine Receptors In The Brain?, Shruti Varshney, Nimish Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is a psychiatric disorder with a pathophysiology that has not yet been fully understood. This mental illness is characterized by disruptions in cognition, social activity, affect, and perception, and affects approximately 0.085% of individuals worldwide. The Alpha 7 Nicotinic Acetylcholine Receptor (α7nAChR) has been connected to auditory function gating deficits. The purpose of this review is to understand the current literature in how the levels of α7nAChR expression and function are affected by SZ, information that could be used to develop therapies to modulate auditory hallucinations in patients with SZ. A literature search was conducted for peer-reviewed journal …

Alpha 7 Nicotinic Acetylcholine Receptor Expression In The Hippocampus Of Patients With Schizophrenia, Shruti Varshney, Ananya Nethikunta, Minjal Patel, Mary Kosciuk, Randel L. Swanson, Venkat Venkataraman, Robert Nagele, Eric Goldwaser, Nimish Acharya

Rowan-Virtua Research Day

Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research …

Loss Of Katnal2 Leads To Ependymal Ciliary Hyperfunction And Autism-Related Phenotypes In Mice, Ryeonghwa Kang, Zachary Papadopoulos, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early …

Effects Of Complete And Partial Loss Of The 24s-Hydroxycholesterol-Generating Enzyme, Hong-Jin Shu, Luke H Ziolkowski, Sofia V Salvatore, Ann M Benz, David F Wozniak, Carla M Yuede, Steven M Paul, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

Brain cholesterol metabolic products include neurosteroids and oxysterols, which play important roles in cellular physiology. In neurons, the cholesterol oxidation product, 24S-hydroxycholesterol (24S-HC), is a regulator of signaling and transcription. Here, we examined the behavioral effects of 24S-HC loss, using global and cell-selective genetic deletion of the synthetic enzyme CYP46A1. Mice that are globally deficient in CYP46A1 exhibited hypoactivity at young ages and unexpected increases in conditioned fear memory. Despite strong reductions in hippocampal 24S-HC in mice with selective loss of CYP46A1 in VGLUT1-positive cells, behavioral effects were not recapitulated in these conditional knockout mice. Global knockout produced strong, developmentally …

Spatial And Amplitude Dynamics Of Neurostimulation: Insights From The Acute Intrahippocampal Kainate Seizure Mouse Model, Thomas J Foutz, Nicholas Rensing, Lirong Han, Dominique M Durand, Michael Wong

2020-Current year OA Pubs

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

RESULTS: …

Dorsal Hippocampus To Nucleus Accumbens Projections Drive Reinforcement Via Activation Of Accumbal Dynorphin Neurons, Khairunisa Mohamad Ibrahim, Nicolas Massaly, Hye-Jean Yoon, Rossana Sandoval, Allie J Widman, Robert J Heuermann, Sidney Williams, William Post, Sulan Pathiranage, Tania Lintz, Azra Zec, Ashley Park, Robert W Gereau 4th, Jose A Morón, Et Al.

2020-Current year OA Pubs

The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the …

Shared And Unique Heritability Of Hippocampal Subregion Volumes In Children And Adults, Jacob G Pine, Arpana Agrawal, Ryan Bogdan, Sridhar Kandala, Shelly Cooper, Deanna M Barch

2020-Current year OA Pubs

Behavioral genetic analyses have not demonstrated robust, unique, genetic correlates of hippocampal subregion volume. Genetic differentiation of hippocampal longitudinal axis subregion volume has not yet been investigated in population-based samples, although this has been demonstrated in rodent and post-mortem human tissue work. The following study is the first population-based investigation of genetic factors that contribute to gray matter volume along the hippocampal longitudinal axis. Twin-based biometric analyses demonstrated that longitudinal axis subregions are associated with significant, unique, genetic variance, and that longitudinal axis subregions are also associated with significant shared, hippocampus-general, genetic factors. Our study's findings suggest that genetic differences …

Chronic Adolescent Stress Alters Gr-Fkbp5 Interactions In The Hippocampus Of Adult Female Rats, Sydney Rowson, Mandakh Bekhbat, Sean Kelly, Molly M Hyer, Samya Dyer, David Weinshenker, Gretchen Neigh

Journal Articles

Chronic stress exposure during development can have lasting behavioral consequences that differ in males and females. More specifically, increased depressive behaviors in females, but not males, are observed in both humans and rodent models of chronic stress. Despite these known stress-induced outcomes, the molecular consequences of chronic adolescent stress in the adult brain are less clear. The stress hormone corticosterone activates the glucocorticoid receptor, and activity of the receptor is regulated through interactions with co-chaperones-such as the immunophilin FK506 binding proteins 5 (FKBP5). Previously, it has been reported that the adult stress response is modified by a history of chronic …

Neural Hyperactivity During Value-Based Decision-Making In People With Daily/Near Daily Cannabis Use, Miranda Ramirez

Theses and Dissertations--Psychology

Value-based decision-making involves the coordinated effort of multiple brain regions to guide future choices based on past experiences. These processes are disrupted in cannabis use disorder, where individuals continue to use cannabis despite negative consequences. Reinforcement learning (RL) paradigms can be used to capture changes in the value of available options and may inform how the brain is impacted by frequent cannabis use. This study combined fMRI with behavioral modeling of probabilistic choice task data to compare value-based choices between young adults reporting daily/near daily cannabis use (CAN) and controls (CTRL). Participants selected one of two options reinforced ($0.25) at …

Effect Of Ficus Carica Leaves Extract On The Hippocampus Of The Aged Rats, Eman Adel Zeair, Ahmed Said Zolfakar, Wael Badr Elkholy, Manar Ali Faried

Menoufia Medical Journal

Objectives: to study the neurodegenerative changes affecting hippocampus of the aged rats compared to young rats and to explore the protective role of Ficus carica (FC) leaves extract. Background: Aging is the progressive accumulation of changes with time. Oxidative stress and low-grade inflammation are the hallmarks of the aging process. Methods: forty male albino rats were divided into four groups of ten rats each: Group I included young animals aged 3 months; group II included rats aged 3 months treated with FC ethanolic extract; group III included rats aged 24 months and group IV included aged rat treated with FC …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

The Herbicide Glyphosate Inhibits Hippocampal Long-Term Potentiation And Learning Through Activation Of Pro-Inflammatory Signaling, Yukitoshi Izumi, Kazuko A O'Dell, Charles F Zorumski

2020-Current year OA Pubs

Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute …

Neuroanatomical And Neurochemical Effects Of Prolonged Social Isolation In Adult Mice, Vibol Heng, Michael Zigmond, Richard Jay Smeyne

Department of Neuroscience Faculty Papers

INTRODUCTION: As social animals, our health depends in part on interactions with other human beings. Yet millions suffer from chronic social isolation, including those in nursing/assisted living facilities, people experiencing chronic loneliness as well as those in enforced isolation within our criminal justice system. While many historical studies have examined the effects of early isolation on the brain, few have examined its effects when this condition begins in adulthood. Here, we developed a model of adult isolation using mice (C57BL/6J) born and raised in an enriched environment.

METHODS: From birth until 4 months of age C57BL/6J mice were raised in …

Platelet-Derived Exerkine Cxcl4/Platelet Factor 4 Rejuvenates Hippocampal Neurogenesis And Restores Cognitive Function In Aged Mice, Odette Leiter, David Brici, Stephen J Fletcher, Xuan Ling Hilary Yong, Jocelyn Widagdo, Nicholas Matigian, Adam B Schroer, Gregor Bieri, Daniel G Blackmore, Perry F Bartlett, Victor Anggono, Saul A Villeda, Tara L Walker

Journal Articles

The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in …

Age-Related Decline In Hippocampal Tyrosine Phosphatase Ptpro Is A Mechanistic Factor In Chemotherapy-Related Cognitive Impairment., Zhimeng Yao, Hongmei Dong, Jianlin Zhu, Liang Du, Yichen Luo, Qing Liu, Shixin Liu, Yusheng Lin, Lu Wang, Shuhong Wang, Wei Wei, Keke Zhang, Qingjun Huang, Xiaojun Yu, Weijiang Zhao, Haiyun Xu, Xiaofu Qiu, Yunlong Pan, Xingxu Huang, Sai-Ching Jim Yeung, Dianzheng Zhang, Hao Zhang

PCOM Scholarly Papers

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are …

Hippocampal Volume And The Detection Of Mild Cognitive Impairment In An Older Adult Population: Assessing Performance On Cognitive Screeners Administered In-Person And Electronically, Kristen Fabrizi

Dissertations

The present study investigated how performance on in-person and electronic neuropsychological assessment measures predicted subcortical hippocampal volume and cognitive decline consistent with mild cognitive impairment. It was hypothesized that the Montreal Cognitive Assessment would display better predictive strength than the Cogstate Brief Battery when evaluating subcortical hippocampal volume measured via structural magnetic resonance imaging. It was further hypothesized that the Montreal Cognitive Assessment would be more sensitive to predicting group membership to the diagnostic classification of mild cognitive impairment compared to the Cogstate Brief Battery. The sample included 445 older adult participants selected from the Alzheimer’s Disease Neuroimaging Initiative 3. …

An Erp Measure Of Non-Conscious Memory Reveals Dissociable Implicit Processes In Human Recognition Using An Open-Source Automated Analytic Pipeline, Richard J. Addante, Javier Lopez-Calderon, Nathan Allen, Carter Luck, Alana Muller, Lindsey Sirianni, Cory S. Inman, Daniel L. Drake

Psychology Student Publications

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = …

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Characterization Of Childhood Trauma, Hippocampal Mediation And Cannabis Use In A Large Dataset Of Psychosis And Non-Psychosis Individuals, Elisabetta C. Del Re, Walid Yassin, Victor Zeng, Sarah Keedy, Ney Alliey-Rodriguez, Elena Ivleva, Scott Hill, Nicole Rychagov, Jennifer E. Mcdowell, Jeffrey R. Bishop

School of Medicine Publications and Presentations

Background

Cannabis use (CA) and childhood trauma (CT) independently increase the risk of earlier psychosis onset; but their interaction in relation to psychosis risk and association with endocannabinoid-receptor rich brain regions, i.e. the hippocampus (HP), remains unclear. The objective was to determine whether lower age of psychosis onset (AgePsyOnset) is associated with CA and CT through mediation by the HP volumes, and genetic risk, as measured by schizophrenia polygene scores (SZ-PGRS).

Methods

Cross-sectional, case-control, multicenter sample from 5 metropolitan US regions. Participants (n = 1185) included 397 controls not affected by psychosis (HC); 209 participants with bipolar disorder type-1; …

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update To The Original Papez Circuit Of The Human Limbic System, Arash Kamali, Sofia Milosavljevic, Anusha Gandhi, Kinsey R Lano, Parnian Shobeiri, Farzaneh Ghazi Sherbaf, Haris I Sair, Roy F Riascos, Khader M Hasan

Journal Articles

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity …

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Glutamate, And Its Relationship To Task-Induced Functional Connectivity In The Human Brain: A Focus On Schizophrenia, Kathleen Liu Young, John Kopchick, Jeffrey Stanley, Vaibhav Diwadkar

Medical Student Research Symposium

Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal …

Allopregnanolone Effects On Inhibition In Hippocampal Parvalbumin Interneurons, Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick

2020-Current year OA Pubs

Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABA

Young Astrocytic Mitochondria Attenuate The Elevated Level Of Ccl11 In The Aged Mice, Contributing To Cognitive Function Improvement, Ryosuke Tashiro, Dan Ozaki, Jesus Bautista-Garrido, Guanghua Sun, Lidiya Obertas, Alexis S Mobley, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung

Journal Articles

Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving …

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene

Ssris Differentially Modulate The Effects Of Pro-Inflammatory Stimulation On Hippocampal Plasticity And Memory Via Sigma 1 Receptors And Neurosteroids, Yukitoshi Izumi, Angela M Reiersen, Eric J Lenze, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely to lipopolysaccharide (LPS), a strong pro-inflammatory stimulus, basal synaptic transmission in the CA1 region remains intact, but induction of long-term potentiation (LTP), a form of synaptic plasticity thought to contribute to learning and memory, is completely …

Adolescence, Alcohol, And Astrocytes: The Impact Of Adolescent Alcohol Use On Astrocyte-Synaptic Interactions, Structure, Function, And Behavior, Christopher Douglas Walker

Theses, Dissertations and Capstones

Alcohol is the third leading cause of preventable death in the United States and has substantial social and economic burdens. Excessive alcohol consumption in the form of binge drinking is highly prevalent among adolescents and emerging adults. Binge drinking is a form of excessive drinking, defined as consuming enough alcohol on a single occasion to result in blood alcohol concentrations above 0.08%. Approximately 55% of full-time college students aged 18- 22 years old have reported consuming alcohol in a binge manner. Furthermore, studies have shown that approximately 20% of college students meet the criteria for an alcohol use disorder (AUD). …

Neurobiology Of Ptsd In Adults And Children: The Impact Of Stress-Induced Brain Abnormalities Across The Lifespan, Catherine Clover

Undergraduate Honors Theses

In the scholarly community, there is disagreement about the effects of PTSD or chronic stress on the brain of adults and children. Though PTSD or chronic stress are known to negatively affect neurobiological structures, specifically due to prolonged glucocorticoid excess, volumetric discrepancies between traumatized and control groups are not unanimously confirmed. This review sought to address the common understandings in academia of the effects of PTSD on the brains of adults and children. Literature on this topic indicated that, in adults, the hippocampus, cingulate gyrus, and prefrontal cortex bilaterally appeared to decrease in gray matter volume and the corpus callosum …

Hippocampal Versus Cortical Deletion Of Cholinergic Receptor Muscarinic 1 In Mice Differentially Affects Post-Translational Modifications And Supramolecular Assembly Of Respiratory Chain-Associated Proteins, Mitochondrial Ultrastructure, And Respiration: Implications In Alzheimer's Disease, Mohammad Golam Sabbir, Mamiko Swanson, Robert C. Speth, Benedict C. Albensi

HPD Articles

In a previous retrospective study using postmortem human brain tissues, we demonstrated that loss of Cholinergic Receptor Muscarinic 1 (CHRM1) in the temporal cortex of a subset of Alzheimer's patients was associated with poor survival, whereas similar loss in the hippocampus showed no such association. Mitochondrial dysfunction underlies Alzheimer's pathogenesis. Therefore, to investigate the mechanistic basis of our findings, we evaluated cortical mitochondrial phenotypes in Chrm1 knockout (Chrm1) mice. Cortical Chrm1 loss resulted in reduced respiration, reduced supramolecular assembly of respiratory protein complexes, and caused mitochondrial ultrastructural abnormalities. These mouse-based findings mechanistically linked cortical CHRM1 loss with poor survival of …