P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice.
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ABSTRACT:
SUBMITTER: Garre JM
PROVIDER: S-EPMC7156443 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice.
Garré Juan Mauricio JM Silva Hernandez Moura HM Lafaille Juan J JJ Yang Guang G
Nature communications 20200414 1
Dysregulated immunity has been implicated in the pathogenesis of neurodevelopmental disorders but its contribution to synaptic and behavioral deficits in Rett syndrome (RTT) remains unknown. P2X7 receptors (P2X7Rs) are unique purinergic receptors with pro-inflammatory functions. Here, we report in a MECP2-deficient mouse model of RTT that the border of the cerebral cortex exhibits increased number of inflammatory myeloid cells expressing cell-surface P2X7Rs. Total knockout of P2X7Rs in MECP2 def ...[more]
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Project description:IntroductionWe aimed to investigate phenotypic heterogeneity in the behavioral variant of frontotemporal dementia (bvFTD) through assessment of inhibition deficits.MethodsWe assessed occurrences of 16 behavioral inhibition deficits from video recordings of 15 bvFTD patients (early stage) and 15 healthy controls (HC) in an ecological setting. We extracted dimensions of inhibition deficit and analyzed their correlations with cognitive and clinical measures. Using these dimensions, we isolated patient clusters whose atrophy patterns were explored.ResultsAfter identifying two patterns of inhibition deficit (compulsive automatic behaviors and socially unconventional behaviors), we isolated three behavioral clusters with distinct atrophy patterns. BvFTD-G0 (N = 3), an outlier group, showed severe behavioral disturbances and more severe ventromedial prefrontal cortex/orbitofrontal cortex atrophy. Compared to bvFTD-G1 (N = 6), bvFTD-G2 (N = 6) presented higher anxiety and depression along with less diffuse atrophy especially in midline regions.DiscussionIdentifying clinico-anatomical profiles through behavior observation could help to stratify bvFTD patients for adapted treatments.
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