Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue

Genetic variance in autism spectrum disorder (ASD) is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated...

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Main Authors: Cheryl Brandenburg, Gene J. Blatt
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2022.838918/full
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author Cheryl Brandenburg
Cheryl Brandenburg
Gene J. Blatt
author_facet Cheryl Brandenburg
Cheryl Brandenburg
Gene J. Blatt
author_sort Cheryl Brandenburg
collection DOAJ
description Genetic variance in autism spectrum disorder (ASD) is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated in ASD. PNNs are found in high density within output structures of the cerebellum and basal ganglia, two regions that are densely connected to many other brain areas and have the potential to participate in the diverse array of symptoms present in an ASD diagnosis. The dentate nucleus (DN) and globus pallidus (GP) were therefore assessed for differences in PNN expression in human postmortem ASD brain tissue. While Purkinje cell loss is a consistent neuropathological finding in ASD, in this cohort, the Purkinje cell targets within the DN did not show differences in number of cells with or without a PNN. However, the density of parvalbumin positive neurons with a PNN were significantly reduced in the GP internus and externus of ASD cases, which was not dependent on seizure status. It is unclear whether these alterations manifest during development or are a consequence of activity-dependent mechanisms that lead to altered network dynamics later in life.
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spelling doaj.art-686ebeda431c4a8b89944d37347cb8cf2022-12-22T02:39:03ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-04-011510.3389/fnmol.2022.838918838918Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain TissueCheryl Brandenburg0Cheryl Brandenburg1Gene J. Blatt2Hussman Institute for Autism, Baltimore, MD, United StatesDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United StatesHussman Institute for Autism, Baltimore, MD, United StatesGenetic variance in autism spectrum disorder (ASD) is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated in ASD. PNNs are found in high density within output structures of the cerebellum and basal ganglia, two regions that are densely connected to many other brain areas and have the potential to participate in the diverse array of symptoms present in an ASD diagnosis. The dentate nucleus (DN) and globus pallidus (GP) were therefore assessed for differences in PNN expression in human postmortem ASD brain tissue. While Purkinje cell loss is a consistent neuropathological finding in ASD, in this cohort, the Purkinje cell targets within the DN did not show differences in number of cells with or without a PNN. However, the density of parvalbumin positive neurons with a PNN were significantly reduced in the GP internus and externus of ASD cases, which was not dependent on seizure status. It is unclear whether these alterations manifest during development or are a consequence of activity-dependent mechanisms that lead to altered network dynamics later in life.https://www.frontiersin.org/articles/10.3389/fnmol.2022.838918/fullperineuronal net (PNN)dentate nucleus of the cerebellumglobus pallidus (GP)autism spectrum disoder (ASD)parvalbumin (PV)
spellingShingle Cheryl Brandenburg
Cheryl Brandenburg
Gene J. Blatt
Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
Frontiers in Molecular Neuroscience
perineuronal net (PNN)
dentate nucleus of the cerebellum
globus pallidus (GP)
autism spectrum disoder (ASD)
parvalbumin (PV)
title Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
title_full Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
title_fullStr Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
title_full_unstemmed Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
title_short Region-Specific Alterations of Perineuronal Net Expression in Postmortem Autism Brain Tissue
title_sort region specific alterations of perineuronal net expression in postmortem autism brain tissue
topic perineuronal net (PNN)
dentate nucleus of the cerebellum
globus pallidus (GP)
autism spectrum disoder (ASD)
parvalbumin (PV)
url https://www.frontiersin.org/articles/10.3389/fnmol.2022.838918/full
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