Ultrastructural remodeling of mitochondria-associated vesicular structures in the rat medial prefrontal cortex...

Propionic acid (PPA), a short-chain fatty acid produced by the gut microbiota, has been implicated in neurodevelopmental and neurological disorders, including autism. The PPA animal model is widely used to investigate mitochondrial dysfunction and associated cellular alterations; however, ultrastructural changes in mitochondrial quality-control pathways, particularly those involving mitochondria-derived vesicles, remain poorly characterized. In the present study, we investigated the effects of a single intraperitoneal injection of PPA on mitochondrial vesicular associations in neurons of the medial prefrontal cortex of adolescent male Wistar rats. Animals were randomly assigned to control (PBS, n = 5) and PPA-treated (175 mg/kg, n = 5) groups. Ten days after treatment, brain tissue was processed for transmission electron microscopy, followed by quantitative morphometric analysis of mitochondria associated with single- and double-membrane vesicular structures in neuronal perikarya, neuronal processes, and pre- and postsynaptic compartments. In control animals, mitochondria associated with single-membrane vesicular structures were more frequently observed than mitochondria associated with double-membrane vesicular structures across all analyzed compartments. PPA exposure produced compartment-specific alterations in these associations, characterized by a significant reduction in mitochondria associated with single-membrane vesicular structures in neuronal perikarya and synaptic compartments, together with an increased number of mitochondria associated with double-membrane vesicular structures in presynaptic terminals. Total mitochondrial number remained unchanged following PPA treatment. These findings demonstrate that PPA induces selective remodeling of mitochondrial-associated vesicular structures in the medial prefrontal cortex without affecting overall mitochondrial abundance. The observed alterations suggest that PPA influences mitochondrial quality-control pathways and reveal ultrastructural changes in mitochondrial vesicular trafficking as a previously underexplored feature of this model. Further studies combining ultrastructural, molecular, and functional approaches are required to determine the mechanisms underlying these changes and their relevance to neurodevelopmental disorders.