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

Mzia G Zhvania; Giorgi Lobzhanidze; Nino Pochkhidze; Nadezhda Japaridze; Pavel Tchelidze; Fuad Rzayev; Eldar Gasimov

doi:10.1016/j.micron.2024.103624

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

Micron. 2024 Jun:181:103624. doi: 10.1016/j.micron.2024.103624. Epub 2024 Mar 4.

Authors

Mzia G Zhvania¹, Giorgi Lobzhanidze², Nino Pochkhidze³, Nadezhda Japaridze⁴, Pavel Tchelidze⁵, Fuad Rzayev⁶, Eldar Gasimov⁶

Affiliations

¹ School of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili Avenue, Tbilisi 0162, Georgia; Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, Tbilisi 0160, Georgia. Electronic address: mzia_zhvania@iliauni.edu.ge.
² Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, Tbilisi 0160, Georgia.
³ School of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili Avenue, Tbilisi 0162, Georgia; Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, Tbilisi 0160, Georgia.
⁴ Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, Tbilisi 0160, Georgia; New Vision University, 1A Evgeni Mikeladze Street, Tbilisi 0159, Georgia.
⁵ New Vision University, 1A Evgeni Mikeladze Street, Tbilisi 0159, Georgia.
⁶ Azerbaijan Medical University, 23 Bakikhanov Street, Baku 1022, Azerbaijan.

PMID: 38492241
DOI: 10.1016/j.micron.2024.103624

Abstract

It is well documented that propionic acid (PPA) produces behavioral, morphological, molecular and immune responses in rats that are characteristic of autism spectrum disorder in humans. However, whether PPA affects the ultrastructure and synaptic architecture of regions of autistic brain has not been adequately addressed. Earlier we show that single intraperitoneal (IP) injection of PPA (175 mg/kg) produces superficial changes in the spatial memory and learning of adolescent male Wistar rats. However, in neurons, synapses and glial cells of hippocampal CA1 area and medial prefrontal cortex transient (mainly) or enduring alterations were detected. In this study, we used electron microscopic morphometric analysis to test the effect of PPA on different structural parameters of axodendritic synapses of the hippocampus and prefrontal cortex. The animals were treated with a single IP injection of PPA (175 mg/kg). The length and width of synaptic active zone, the area of presynaptic and postsynaptic mitochondria, the distance between presynaptic mitochondria and the synapse active zone, the distance between postsynaptic mitochondria and postsynaptic density and the depth and opening diameter of neuronal porosome complex were evaluated. Our results show that synaptic mitochondria of the hippocampus and prefrontal cortex are the most vulnerable to PPA treatment: in both regions, the area of postsynaptic mitochondria were increased. In general, our results show that even small dose of PPA, which produces only superficial effects on spatial memory and learning is able to alter the synapse architecture in brain regions involved in cognition and autism pathogenesis. Therefore, the microbiome may be involved in the control of neurotransmission in these regions.

Keywords: Adolescent male rats; Hippocampus; Prefrontal cortex; Propionic acid; Synapse architecture.