Objective: This study delineates the age-dependent susceptibility of hippocampal CA1 circuits to chronic toluene toxicity, specifically investigating whether synaptic degradation is reversible or marks the onset of persistent neurodegenerative alterations.

Background: Chronic toluene inhalation triggers neurodegenerative cascades, often manifesting as progressive movement disorders and cognitive decline. Despite an established neurotoxic profile, the hippocampal capacity for ultrastructural restoration remains undefined, particularly regarding the resilience gap between the developing and the adult brain.

Method: Adolescent (PND 25-30) and adult (PND 90-95) male rats underwent chronic toluene exposure (2000 ppm) for 40 days. Behavioral assessments via the Barnes Maze were conducted 24 hours post-exposure (acute toxicity) and after a 90-day washout period (to evaluate late-stage persistent deficits). High-resolution morphometric analysis of the CA1 region was performed using Transmission Electron Microscopy (TEM) to quantify synaptic vesicle docking, PSD thickness, and mitochondrial integrity.

Results: Results demonstrate a stark divergence in hippocampal recovery trajectories. While immediate cognitive-motor impairment was evident in both cohorts ($p < 0.05$), adult rats exhibited structural recovery of synaptic integrity after the 90-day washout period. Conversely, the adolescent group displayed irreversible pathological hallmarks: a persistent reduction in docked vesicles and PSD thinning, which correlated with a failure in long-term spatial strategy acquisition despite the extended recovery timeframe.

Conclusion: Adolescent toluene exposure induces permanent structural-functional dissociation in hippocampal networks. Unlike the fully developed brain, the developing synaptic architecture lacks the regenerative capacity to surmount chronic toxic insult, leading to lifelong neurobiological deficits. These findings highlight a critical window of vulnerability and necessitate age-specific neuroprotective strategies.

References: This work was supported by the Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [Grant Number YS-24-194].

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-related-susceptibility-of-hippocampal-synaptic-ultrastructure-and-spatial-cognition-to-chronic-toluene-exposure-a-comparative-study-of-immediate-and-long-term-effects/