Cell and Developmental Biology Commons^™

A Review Of The Neural Basis Underlying The Acoustic Startle Response With A Focus On Recent Developments In Mammals, Alice Zheng, Susanne Schmid

Anatomy and Cell Biology Publications

The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is evolutionarily preserved and can be observed in any animal that can perceive sensory signals, indicating the important protective function of startle. Startle response measurements and its alterations have become a valuable tool for exploring sensorimotor processes and sensory gating, especially in the context of pathologies of psychiatric disorders. The last reviews on the neural substrates underlying acoustic startle were published around 20 years ago. Advancements in methods and techniques have since allowed new insights into acoustic startle …

Spatiotemporally Dynamic Electric Fields For Brain Cancer Treatment: An In Vitro Investigation, Erin Iredale, Abdulla Elsaleh, Hu Xu, Paul Christiaans, Andrew Deweyert, John Ronald, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

Objective. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm^-1) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation. In this study, we employed computer simulations to generate spatiotemporally dynamic electric fields, designed and purpose-built an IMT device for in vitro experiments, and evaluated the human GBM cellular responses to these fields. Approach. After measuring the electrical conductivity of the in vitro culturing medium, we designed experiments to evaluate the …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …

Characterizing Maternal Isolation-Induced Ultrasonic Vocalizations In A Gene-Environment Interaction Rat Model For Autism., Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L Haddad, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and …

Investigating Behavioral Phenotypes Related To Autism Spectrum Disorder In A Gene-Environment Interaction Model Of Cntnap2 Deficiency And Poly I:C Maternal Immune Activation, Faraj L Haddad, Cleusa De Oliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Introduction: Autism Spectrum Disorder (ASD) has been associated with a wide variety of genetic and environmental risk factors in both human and preclinical studies. Together, findings support a gene-environment interaction hypothesis whereby different risk factors independently and synergistically impair neurodevelopment and lead to the core symptoms of ASD. To date, this hypothesis has not been commonly investigated in preclinical ASD models. Mutations in the Contactin-associated protein-like 2 (Cntnap2) gene and exposure to maternal immune activation (MIA) during pregnancy have both been linked to ASD in humans, and preclinical rodent models have shown that both MIA and Cntnap2 deficiency …

Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in …

Planning System For The Optimization Of Electric Field Delivery Using Implanted Electrodes For Brain Tumor Control, Erin Iredale, Brynn Voigt, Adam Rankin, Kyungho W Kim, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

BACKGROUND: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

PURPOSE: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT. The practicality of the treatment planning system is demonstrated by implementing the full optimization pipeline on a brain phantom with robotic electrode implantation, postoperative imaging, and treatment stimulation.

METHODS: The integrated planning pipeline in 3D Slicer begins with importing and segmenting patient magnetic resonance images (MRI) or computed tomography (CT) images. The segmentation process is manual, followed by a semi-automatic smoothing step that allows …

Gabab Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity And Filtering In The Cntnap2 Knock-Out Rat, Dorit Möhrle, Wenxuan Wang, Shawn N Whitehead, Susanne Schmid

Anatomy and Cell Biology Publications

Altered sensory information processing, and auditory processing, in particular, is a common impairment in individuals with autism spectrum disorder (ASD). One prominent hypothesis for the etiology of ASD is an imbalance between neuronal excitation and inhibition. The selective GABA_B receptor agonist R-Baclofen has been shown previously to improve social deficits and repetitive behaviors in several mouse models for neurodevelopmental disorders including ASD, and its formulation Arbaclofen has been shown to ameliorate social avoidance symptoms in some individuals with ASD. The present study investigated whether R-Baclofen can remediate ASD-related altered sensory processing reliant on excitation/inhibition imbalance in the auditory brainstem. …

A Systematic Review Of Brainstem Contributions To Autism Spectrum Disorder, Ala Seif, Carly Shea, Susanne Schmid, Ryan A Stevenson

Anatomy and Cell Biology Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review …

Sensory Filtering Disruption Caused By Poly I:C - Timing Of Exposure And Other Experimental Considerations., Faraj L Haddad, Lu Lu, Kelly J Baines, Susanne Schmid

Anatomy and Cell Biology Publications

Maternal immune activation (MIA) in response to infection during pregnancy has been linked through various epidemiological and preclinical studies to an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia in exposed offspring. Sensory filtering disruptions occur in both of these disorders and are typically measured using the acoustic startle response in both humans and rodents. Our study focuses on characterizing the baseline reactivity, habituation and prepulse inhibition (PPI) of the acoustic startle response following exposure to MIA. We induced MIA using polyinosinic: polycytidylic acid (poly I:C) at gestational day (GD) 9.5 or 14.5, and we …

Pannexin 1 Inhibition Delays Maturation And Improves Development Of Bos Taurus Oocytes, Zachary Timothy Dye, Lauren Virginia Rutledge, Silvia Penuela, Paul William Dyce

Anatomy and Cell Biology Publications

© 2020 The Author(s). Background: Intercellular exchange between the oocyte and its surrounding cells within the follicular environment is critical for oocyte maturation and subsequent development. In vertebrates this exchange is facilitated through gap junctions formed by connexin membrane proteins. Another family of membrane proteins called pannexins are able to form single membrane channels that allow cellular exchanges with the extracellular environment. The most ubiquitously expressed and studied member, pannexin 1 (PANX1), has yet to be described thoroughly in female reproductive tissues or functionally studied during oocyte maturation. Here, we look into the expression of pannexin 1 in bovine cumulus-oocyte …

Consideration Of Pannexin 1 Channels In Covid-19 Pathology And Treatment, Leigh Anne Swayne, Scott R. Johnstone, Chen Seng Ng, Juan C. Sanchez-Arias, Miranda E. Good, Silvia Penuela, Alexander W. Lohman, Abigail G. Wolpe, Victor E. Laubach, X. Michael Koval, Brant E. Isakson

Anatomy and Cell Biology Publications

Copyright © 2020 the American Physiological Society Pannexin 1 (PANX1) is a ubiquitously expressed, channel-forming protein found in a number of tissues throughout the body (e.g., lung, vasculature, liver, central nervous system, immune system) that is important in many key physiological and immune responses (18, 55). PANX1 channels passively flux ATP (predominantly), multiple metabolites, and likely other small anions (37, 39). PANX1 channels regulate inflammation and host responses to several pathogens, including viruses (36, 42, 53). While there is currently no evidence suggesting novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PANX1 directly interact, there is an urgent need …

What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that are caused by genetic and/or environmental impacts, often probably by the interaction of both. They are characterised by deficits in social communication and interaction and by restricted and repetitive behaviours and interests from early childhood on, causing significant impairment. While it is clear that no animal model captures the full complexity of ASD in humans, genetic models are extremely useful for studying specific symptoms associated with ASD and the underlying cellular and molecular mechanisms. In this review we summarize the behavioral paradigms used in rodents to model ASD symptoms as they …

Pathological Changes In Microvascular Morphology, Density, Size And Responses Following Comorbid Cerebral Injury, Zareen Amtul, Jun Yang, Ting-Yim Lee, David F. Cechetto

Anatomy and Cell Biology Publications

Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and A beta deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of beta-amyloid (A beta) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 …

Pathological Changes In Microvascular Morphology, Density, Size And Responses Following Comorbid Cerebral Injury, Zareen Amtul, Jun Yang, Ting-Yim Lee, David F. Cechetto

Anatomy and Cell Biology Publications

Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer’s disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of β-amyloid (Aβ) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The …

Moderating Effect Of Cortical Thickness On Bold Signal Variability Age-Related Changes, Daiana R. Pur, Roy Eagleson, Anik De Ribaupierre, Nathalie Mella, Sandrine De Ribaupierre

Anatomy and Cell Biology Publications

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or "BOLDSD", is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between …

Ablation Of Both Cx40 And Panx1 Results In Similar Cardiovascular Phenotypes Exhibited In Cx40 Knockout Mice, Nicole M. Novielli-Kuntz, Meghan L. Jelen, Kevin Barr, Leon J. Delalio, Qingping Feng, Brant E. Isakson, Robert Gros, Dale Laird

Anatomy and Cell Biology Publications

Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore channel-forming proteins that participate in cellular communication via small molecular exchange with the extracellular microenvironment, or in the case of connexins, directly between cells. Given the putative functional overlap between single membrane-spanning connexin hemichannels and Panx channels, and cardiovascular system prevalence, we generated the first Cx40(-/-)Panx1(-/-) mouse with the anticipation that this genetic modification would lead to a severe cardiovascular phenotype. Mice null for both Cx40 and Panx1 produced litter sizes and adult growth progression similar to wild-type (WT), Cx40(-/-) and Panx1(-/-) mice. Akin to Cx40(-/-) mice, Cx40(-/-) Panx1(-/-) mice exhibited …

Predicting Alzheimer’S Disease Progression Using Multi-Modal Deep Learning Approach, Garam Lee, Kwangsik Nho, Byungkon Kang, Kyung-Ah Sohn, Dokyoon Kim, Alzheimer's Disease Neuroimaging Initiative

Anatomy and Cell Biology Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer’s Disease Neuroimaging …

Fluctuation Of Primary Motor Cortex Excitability During Cataplexy In Narcolepsy, Bei Huang, Zhenying Qian, Zongwen Wang, Jihui Zhang, Kun Chen, Tao Xu, Jijun Wang, David F. Cechetto, Zhongxin Zhao, Huijuan Wu

Anatomy and Cell Biology Publications

Objective Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results Based on the video and electromyogram observations, a typical cataplectic …

Detection Of Active Caspase-3 In Mouse Models Of Stroke And Alzheimer's Disease With A Novel Dual Positron Emission Tomography/Fluorescent Tracer [68ga]Ga-Tc3-Ogdota., Valeriy G Ostapchenko, Jonatan Snir, Mojmir Suchy, Jue Fan, M.Rebecca Cobb, Blaine Chronik, Michael Kovacs, Vania F. Prado, Robert H.E. Hudson, Stephen H. Pasternak, Marco A.M. Prado, Robert Bartha

Anatomy and Cell Biology Publications

Apoptosis is a feature of stroke and Alzheimer's disease (AD), yet there is no accepted method to detect or follow apoptosis in the brain in vivo. We developed a bifunctional tracer [Ga-68]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and Ga-68-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [Ga-68]Ga-TC3-OGDOTA to accumulate in apoptotic cells. In vitro, Ga-TC3-OGDOTA labeled apoptotic neurons following exposure to camptothecin, oxygen-glucose deprivation, and -amyloid oligomers. In vivo, PET showed accumulation of [Ga-68]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of …

Dissociable Cognitive Impairments In Two Strains Of Transgenic Alzheimer's Disease Mice Revealed By A Battery Of Object-Based Tests, Samantha D. Creighton, Ari L. Mendell, Daniel Palmer, Bettina E. Kalisch, Neil J. Maclusky, Vania F Prado, Marco A.M Prado, Boyer D. Winters

Anatomy and Cell Biology Publications

Object recognition tasks detect cognitive deficits in transgenic Alzheimer's disease (AD) mouse models. Object recognition, however, is not a unitary process, and there are many uncharacterized facets of object processing with relevance to AD. We therefore systematically evaluated object processing in 5xFAD and 3xTG AD mice to clarify the nature of object recognition-related deficits. Twelve-month-old male and female 5xFAD and 3xTG mice were assessed on tasks for object identity recognition, spatial recognition, and multisensory object perception. Memory and multisensory perceptual impairments were observed, with interesting dissociations between transgenic AD strains and sex that paralleled neuropathological changes. Overreliance on the widespread …

Effects Of Prenatal Exercise On Fetal Heart Rate, Umbilical And Uterine Blood Flow: A Systematic Review And Meta-Analysis, Rachel J. Skow, Margie H. Davenport, Michelle Mottola, Gregory A. Davies, Veronica J. Poitras, Casey E. Gray, Alejandra Jaramillo Garcia, Nick Barrowman, Victoria L. Meah, Linda G. Slater, Kristi B. Adamo, Ruben Barakat, Stephanie-May Ruchat

Anatomy and Cell Biology Publications

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics.

Design Systematic review with random-effects meta-analysis and meta-regression.

Data sources Online databases were searched up to 6 January 2017.

Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other …

Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable To Low Intensity Electric Fields Delivered By Intratumoral Modulation Therapy, Andrew Deweyert, Erin Iredale, Hu Xu, Eugene Wong, Susanne Schmid, Matthew O. Hebb

Anatomy and Cell Biology Publications

Introduction

Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT).

Methods

DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. …

Double Deletion Of Panx1 And Panx3 Affects Skin And Bone But Not Hearing, J M. Abitbol, B L. O'Donnell, C B. Wakefield, E Jewlal, J J. Kelly, K Barr, K E. Willmore, B. L. Allman, S Penuela

Anatomy and Cell Biology Publications

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). …

First M87 Event Horizon Telescope Results. I. The Shadow Of The Supermassive Black Hole, Aaron Faber, Kazunori Akiyama, Antxon Alberdi, Walter Alef, Keiichi Asada, Rebecca Azulay, Anne-Kathrin Baczko, David Ball, Mislav Baloković, John Barrett, Dan Bintley

Anatomy and Cell Biology Publications

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, …

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …

Linked Mri Signatures Of The Brain's Acute And Persistent Response To Concussion In Female Varsity Rugby Players, Kathryn Y. Manning, Alberto Llera, Gregory A Dekaban, Robert Bartha, Christy Barreira, Arthur Brown, Lisa Fischer, Tatiana Jevremovic, Kevin A. Blackney, Tim Doherty, Douglas D. Fraser, Jeff Holmes, Christian F. Beckmann, Ravi S. Menon

Anatomy and Cell Biology Publications

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of …

Inhibition Of Pannexin 1 Reduces The Tumorigenic Properties Of Human Melanoma Cells, Taylor J. Freeman, Samar Sayedyahossein, Rafael E. Sanchez-Pupo, Brooke O'Donnell, Kenneth Huang, Zameena Lakhani, Daniel Nouri-Nejad, Kevin J. Barr, Luke Harland, Steven Latosinsky, Aaron Grant, Lina Dagnino, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment …

The Connexin 30 A88v Mutant Reduces Cochlear Gap Junction Expression And Confers Long-Term Protection Against Hearing Loss, John J. Kelly, Julia Abitbol, Stephanie Hulme, Eric R. Press, Dale Laird, Brian L. Allman

Anatomy and Cell Biology Publications

Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2) and Cx30 (GJB6) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30(A88V/A88V) mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant …