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2018

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Full-Text Articles in Medical Neurobiology

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19 Nov 2018

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.


Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya Oct 2018

Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …


Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman Oct 2018

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …


Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu Oct 2018

Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu

Biomedical Sciences

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 …


In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik Sep 2018

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …


Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria Sep 2018

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …


Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes Aug 2018

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …


Predicting Gains With Visuospatial Training After Stroke Using An Eeg Measure Of Frontoparietal Circuit Function, Robert J. Zhou, Hossein M. Hondori, Maryam Khademi, Jessica M. Cassidy, Katherine M. Wu, Derek Z. Yang, Nikhita Kathuria, Fareshte R. Erani, Lucy Dodakian, Alison Mckenzie, Cristina V. Lopes, Walt Scacchi, Ramesh Srinivasan, Steven C. Cramer Jul 2018

Predicting Gains With Visuospatial Training After Stroke Using An Eeg Measure Of Frontoparietal Circuit Function, Robert J. Zhou, Hossein M. Hondori, Maryam Khademi, Jessica M. Cassidy, Katherine M. Wu, Derek Z. Yang, Nikhita Kathuria, Fareshte R. Erani, Lucy Dodakian, Alison Mckenzie, Cristina V. Lopes, Walt Scacchi, Ramesh Srinivasan, Steven C. Cramer

Physical Therapy Faculty Articles and Research

The heterogeneity of stroke prompts the need for predictors of individual treatment response to rehabilitation therapies. We previously studied healthy subjects with EEG and identified a frontoparietal circuit in which activity predicted training-related gains in visuomotor tracking. Here we asked whether activity in this same frontoparietal circuit also predicts training-related gains in visuomotor tracking in patients with chronic hemiparetic stroke. Subjects (n = 12) underwent dense-array EEG recording at rest, then received 8 sessions of visuomotor tracking training delivered via home-based telehealth methods. Subjects showed significant training-related gains in the primary behavioral endpoint, Success Rate score on a standardized test …


Cdk5 Inhibition Resolves Pka/Camp-Independent Activation Of Creb1 Signaling In Glioma Stem Cells, Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J. Brat May 2018

Cdk5 Inhibition Resolves Pka/Camp-Independent Activation Of Creb1 Signaling In Glioma Stem Cells, Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J. Brat

Neurology Faculty Publications

Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation. Our investigation revealed that pharmaceutical inhibition of CDK5 prevents GSC self-renewal in vitro and in xenografted tumors, at …


Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz May 2018

Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz

Psychology Faculty Articles and Research

Objective: We propose that clinicians can use suggestion to help treat conditions such as ADHD. Methods: We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. Results: The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Conclusion: Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential …


Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin May 2018

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …


Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi Apr 2018

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.


Network Specialization During Adolescence: Hippocampal Effective Connectivity In Boys And Girls, Jeffrey D. Riley, E. Elinor Chen, Jessica Winsell, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram, Curt A. Sandman, Steven L. Small, Ana Solodkin Apr 2018

Network Specialization During Adolescence: Hippocampal Effective Connectivity In Boys And Girls, Jeffrey D. Riley, E. Elinor Chen, Jessica Winsell, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram, Curt A. Sandman, Steven L. Small, Ana Solodkin

Psychology Faculty Articles and Research

Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8–16 years old, divided into younger (ages 8–10) and older (ages …


Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta Mar 2018

Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta

Pharmacy Faculty Articles and Research

BACKGROUND

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

METHODS

Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds …


Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall Mar 2018

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …


Aging Exacerbates Development Of Cerebral Microbleeds In A Mouse Model, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Annlia Paganini-Hill, Kelley Kilday, Ronald Kim, David H. Cribbs, Mark J. Fisher Mar 2018

Aging Exacerbates Development Of Cerebral Microbleeds In A Mouse Model, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Annlia Paganini-Hill, Kelley Kilday, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age.

Methods: We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 …


Cortical Thinning And Neuropsychiatric Outcomes In Children Exposed To Prenatal Adversity: A Role For Placental Crh?, Curt A. Sandman, Megan M. Curran, Elyssia Poggi Davis, Laura M. Glynn, Kevin Head, Tallie Z. Baram Mar 2018

Cortical Thinning And Neuropsychiatric Outcomes In Children Exposed To Prenatal Adversity: A Role For Placental Crh?, Curt A. Sandman, Megan M. Curran, Elyssia Poggi Davis, Laura M. Glynn, Kevin Head, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity may disrupt the development and maturation of neurons and brain circuits, which, in turn, underlie neurodevelopment and mental illnesses. During fetal life, maternal adversity is conveyed to the developing brain via several molecular signals, including the stress hormone corticotropin releasing hormone (CRH). Employing a large well characterized prospective cohort, we find that fetal exposure to placental-origin CRH levels predicts structural and functional brain outcomes in children. Specifically, elevated placental CRH levels portend thinning of selective cortical regions of exposed individuals, with commensurate cognitive and emotional deficits. Notably, the relations of placental-origin CRH to cortical thinning …


Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke Feb 2018

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …


Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich Feb 2018

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion …


Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory, Yousseff Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini D. Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein Feb 2018

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory, Yousseff Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini D. Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein

Dartmouth Scholarship

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …


Trpm7 Current Inactivation: Evidence For Inside-Out Signaling, Tetyana Zhelay, J. Ashot Kozak Feb 2018

Trpm7 Current Inactivation: Evidence For Inside-Out Signaling, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 channels conduct metal cations such as Na+, K+, Ca2+ and Mg2+. In the presence of external Ca2+/Mg2+ TRPM7 has a steeply outwardly rectifying current-voltage (I-V) relation. In the absence of Ca2+/Mg2+ the IV becomes semi-linear. This has been explained by the removal of pore blockade by divalent cations (e.g. Ca2+o/Mg2+o). TRPM7 channels are inhibited by cytoplasmic Mg2+ in a voltage-independent manner, primarily by a reversible reduction in the overall number of conducting channels. Here, we have examined the consequences of external Ca2+ removal and reintroduction on TRPM7 current kinetics. In whole-cell patch clamp with low internal Mg2+, we rapidly …


Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio Jan 2018

Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio

School of Medicine Faculty Publications

Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic …


Exposure To Mild Blast Forces Induces Neuropathological Effects, Neurophysiological Deficits And Biochemical Changes, Adan Hernandez, Chunfeng Tan, Florian Plattner, Aric F. Logsdon, Karine Pozo, Mohammad A. Yousuf, Tanvir Singh, Ryan C. Turner, Brandon P. Luke-Wold, Jason D. Huber, Charles L. Rosen, James A. Bibb Jan 2018

Exposure To Mild Blast Forces Induces Neuropathological Effects, Neurophysiological Deficits And Biochemical Changes, Adan Hernandez, Chunfeng Tan, Florian Plattner, Aric F. Logsdon, Karine Pozo, Mohammad A. Yousuf, Tanvir Singh, Ryan C. Turner, Brandon P. Luke-Wold, Jason D. Huber, Charles L. Rosen, James A. Bibb

Faculty & Staff Scholarship

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces …


Three-Dimensional Imaging Of Kndy Neurons In The Mammalian Brain Using Optical Tissue Clearing And Multiple-Label Immunocytochemistry, Aleisha M. Moore, Kathryn A. Lucas, Robert L. Goodman, Lique M. Coolen, Michael N. Lehman Jan 2018

Three-Dimensional Imaging Of Kndy Neurons In The Mammalian Brain Using Optical Tissue Clearing And Multiple-Label Immunocytochemistry, Aleisha M. Moore, Kathryn A. Lucas, Robert L. Goodman, Lique M. Coolen, Michael N. Lehman

Faculty & Staff Scholarship

Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO. This study expands the use of …


The Potential Synergistic Behaviour Of Inter- And Intra-Genus Probiotic Combinations In The Pattern And Rate Of Short Chain Fatty Acids Formation During Fibre Fermentation, Warnakulasuriya M. A. D. B. Fernando, Steve H. Flint, K. K. D. S. Ranaweera, Arthur Bamunuarachchi, Stuart K. Johnson, Charles S. Brennan Jan 2018

The Potential Synergistic Behaviour Of Inter- And Intra-Genus Probiotic Combinations In The Pattern And Rate Of Short Chain Fatty Acids Formation During Fibre Fermentation, Warnakulasuriya M. A. D. B. Fernando, Steve H. Flint, K. K. D. S. Ranaweera, Arthur Bamunuarachchi, Stuart K. Johnson, Charles S. Brennan

Research outputs 2014 to 2021

This study compared the rate of short chain fatty acid (SCFA) production by different probiotic combinations of Lactobacillus and Bifidobacterium to determine any synergistic effects. Six different fibre fractions were fermented with nine combinations of Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA), Bifidobacterium longum (BL) and Bifidobacterium breve (BB) for 0, 6, 24 and 48 h. SCFAs were quantified by gas chromatography. Inter-genus combinations of bacteria produced more SCFA, especially BB + BL + LR, compared to intra-genus that yielded the lowest SCFA production. Acetate was the most abundant, while propionate and butyrate were the most utilised. The SCFA formation was …


Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman Jan 2018

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …


Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler Jan 2018

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …


A Gut Feeling: A Hypothesis Of The Role Of The Microbiome In Attention-Deficit/Hyperactivity Disorders., Xue Ming, Neil Chen, Carly Ray, Gretchen Brewer, Jeffrey Kornitzer, Robert A Steer Jan 2018

A Gut Feeling: A Hypothesis Of The Role Of The Microbiome In Attention-Deficit/Hyperactivity Disorders., Xue Ming, Neil Chen, Carly Ray, Gretchen Brewer, Jeffrey Kornitzer, Robert A Steer

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Attention-deficit/hyperactivity disorder (ADHD) is a neurologic disorder characterized by hyperactivity/impulsivity and/or inattentiveness, with genetic and environmental factors contributing to the disorder. With the growing recognition of the microbiome's role in many neurological disorders, the authors propose that it may also be implicated in ADHD. Here, we describe several evolving areas of research to support this hypothesis. First, a unique composition of gut bacteria has been identified and linked to behaviors in ADHD. Second, our research found an increased incidence of 2 gastrointestinal symptoms (constipation and flatulence) in children with ADHD, as compared to controls. Finally, emerging data may be interpreted …