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Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism
Author(s) -
Lobzhanidze Giorgi,
Japaridze Nadezhda,
Lordkipanidze Tamar,
Rzayev Fuad,
MacFabe Derrick,
Zhvania Mzia
Publication year - 2020
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1002/jdn.10011
Subject(s) - hippocampus , hippocampal formation , butyrate , synapse , systemic administration , microglia , ultrastructure , neuroscience , prefrontal cortex , pyramidal cell , biology , synaptic vesicle , mitochondrion , endocrinology , medicine , microbiology and biotechnology , biochemistry , anatomy , inflammation , cognition , vesicle , membrane , fermentation , in vivo
Abstract Short chain fatty acids, produced as gut microbiome metabolites but also present in the diet, exert broad effects in host physiology. Propionic acid (PPA), along with butyrate and acetate, plays a growing role in health, but also in neurological conditions. Increased PPA exposure in humans, animal models and cell lines elicit diverse behavioural and biochemical changes consistent with organic acidurias, mitochondrial disorders and autism spectrum disorders (ASD). ASD is considered a disorder of synaptic dysfunction and cell signalling, but also neuroinflammatory and neurometabolic components. We examined behaviour (Morris water and radial arm mazes) and the ultrastructure of the hippocampus and medial prefrontal cortex (electron microscopy) following a single intraperitoneal (i.p.) injection of PPA (175 mg/kg) in male adolescent rats. PPA treatment showed altered social and locomotor behaviour without changes in learning and memory. Both transient and enduring ultrastructural alterations in synapses, astro‐ and microglia were detected in the CA1 hippocampal area. Electron microscopic analysis showed the PPA treatment significantly decreased the total number of synaptic vesicles, presynaptic mitochondria and synapses with a symmetric active zone. Thus, brief systemic administration of this dietary and enteric short chain fatty acid produced behavioural and dynamic brain ultrastructural changes, providing further validation of the PPA model of ASD.