Chronic formaldehyde inhalation reduces parvalbumin immunoreactivity and modulates glial activation in the rat brain

Formalin is the principal fixative used in gross anatomy dissection, and its vapour (formaldehyde) constitutes a recognised occupational hazard for anatomists, technicians, and students during prolonged cadaveric exposure. While the respiratory and mucosal effects of formaldehyde inhalation are well documented, its impact on the brain’s cellular architecture, particularly on fast-spiking, parvalbumin-expressing interneurons that regulate cortical and hippocampal network activity, remains poorly characterised under a chronic, inhalation-based, exposure paradigm exceeding typical modern occupational breathing-zone concentrations, modelling a high-exposure/worst-case scenario relevant to poorly ventilated or historically under-regulated dissection settings. This study examined the neuroanatomical consequences of 28-day formaldehyde inhalation in adult male Wistar rats. Exposed animals showed a significant, time-dependent decline in body weight gain, a reduction in absolute brain weight, and an elevation in brain formaldehyde concentration relative to controls. Neurobehavioral testing revealed impaired motor coordination, spatial memory, and exploratory behaviour. Formaldehyde-exposed brains showed significantly elevated lipid peroxidation and depleted antioxidant enzyme activities. Quantitative immunohistochemical and morphometric analysis revealed a marked reduction in the number and soma size of parvalbumin-expressing interneurons in the cerebellar Purkinje layer, hippocampal CA1 region, and cerebral cortex, accompanied by pronounced astrocytic and microglial activation across these regions and the olfactory bulb. Because this pattern was observed in every region and layer examined rather than in a subset of regions, these findings indicate that chronic formaldehyde inhalation produces measurable, widespread neurodegeneration and neuroinflammation in a rodent model that closely mirrors occupational exposure conditions in anatomy dissection settings. The results underscore the need for stricter formaldehyde exposure controls in anatomical education and raise concern regarding the long-term neurological safety of personnel routinely exposed to formalin vapour in dissection halls. As only male rats were examined, the generalizability of these findings to female subjects remains to be established.