Influence of Chronic Electroconvulsive Seizures on Plasticity-Associated Gene Expression and Perineuronal Nets Within the Hippocampi of Young Adult and Middle-Aged Sprague-Dawley Rats

Abstract

Background Electroconvulsive seizure therapy is often used in both treatment-resistant and geriatric depression. However, preclinical studies identifying targets of chronic electroconvulsive seizure (ECS) are predominantly focused on animal models in young adulthood. Given that putative transcriptional, neurogenic and neuroplastic mechanisms implicated in the behavioral effects of chronic ECS themselves exhibit age-dependent modulation, it remains unknown whether the molecular and cellular targets of chronic ECS vary with age. Methods We subjected young adult (2 – 3 months) and middle-aged (12 – 13 months), male Sprague Dawley rats to sham or chronic ECS, and assessed for despair-like behaviour, hippocampal gene expression, hippocampal neurogenesis, and neuroplastic changes in the extracellular matrix, reelin and perineuronal net (PNN) numbers. Results Chronic ECS reduced despair-like behavior at both ages, accompanied by overlapping and unique changes in activity-dependent and trophic factor gene expression. Whilst chronic ECS had a similar impact on quiescent neural progenitor numbers at both ages, the eventual increase in hippocampal progenitor proliferation was substantially higher in young adulthood. We noted a decline in reelin⁺ cell numbers following chronic ECS only in young adulthood. In contrast, an age-invariant, robust dissolution of PNNs that encapsulate parvalbumin⁺ neurons in the hippocampus was observed following chronic ECS. Conclusion Our findings indicate that age is a key variable in determining the nature of chronic ECS evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioural changes in an age-dependent manner.

Electroconvulsive therapy increases cortical thickness in depression: A systematic review

“…Surprisingly, however, both pretreatment CT and the early increase in CT seem to represent predictive biomarkers of the clinical response to antidepressants(Phillips et al, 2015) suggesting that various processes can underlie its clinical effectiveness. Neuroplasticity, including the processes of neurogenesis, synaptogenesis, dendrogenesis, gliogenesis, and angiogenesis, has been hypothesised to be the biological mechanism for the effects of ECT on CT (Hellsten et al, 2005; Jaggar et al, 2023; Wennström et al, 2004; Zhang et al, 2023). In particular, animal studies have reported that rats subjected to electroconvulsive stimulation show increased genesis of hippocampal neurons with the potential for long-term survival (Altar et al, 2003; Madsen et al, 2005; Olesen et al, 2017).…”