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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Propionic acid affects the synaptic architecture of rat hippocampus and prefrontal cortex
Mzia G Zhvania1, Giorgi Lobzhanidze2, Nino Pochkhidze1
1School 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.
Insights
Propionic acid (PPA) exposure alters synapse structure in rat brain regions linked to autism. Even low doses impact mitochondrial size in the hippocampus and prefrontal cortex, suggesting potential links to cognitive function.
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.
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.
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