Propionic acid affects the synaptic architecture of rat hippocampus and prefrontal cortex

Area of Science:

• Neuroscience
• Autism Spectrum Disorder Research
• Toxicology

Background:

• Propionic acid (PPA) exposure in rats mimics autism spectrum disorder (ASD) characteristics.
• Previous studies show PPA causes behavioral and molecular changes, but its effect on brain ultrastructure is less understood.
• Investigating PPA's impact on synaptic architecture in brain regions relevant to ASD is crucial.

Purpose of the Study:

• To investigate the effects of propionic acid (PPA) on the ultrastructure and synaptic architecture of the hippocampus and medial prefrontal cortex.
• To quantitatively assess PPA's impact on specific axodendritic synapse parameters using electron microscopy.
• To determine if PPA alters neuronal and glial cell structures in brain regions implicated in cognitive function and autism.

Main Methods:

• Adolescent male Wistar rats received a single intraperitoneal injection of propionic acid (PPA) at 175 mg/kg.
• Electron microscopic morphometric analysis was employed to evaluate synaptic parameters.
• Key parameters assessed included synaptic active zone dimensions, mitochondrial area and proximity, and neuronal porosome complex characteristics.

Main Results:

• Postsynaptic mitochondria area significantly increased in both the hippocampus and medial prefrontal cortex following PPA treatment.
• Synaptic mitochondria were identified as the most vulnerable cellular component to PPA exposure.
• Even doses of PPA causing only minor spatial memory deficits induced alterations in synapse architecture.

Conclusions:

• Propionic acid (PPA) significantly alters synaptic architecture in the hippocampus and medial prefrontal cortex, even at doses with subtle behavioral effects.
• The observed changes in synaptic mitochondria suggest a direct impact on neuronal function and energy metabolism.
• These findings highlight PPA's potential role in neurodevelopmental alterations relevant to autism pathogenesis and suggest a possible link to microbiome-mediated neurotransmission control.