Exploring Autophagy Dynamics and Cell Death Signaling in Chronic Methamphetamine-Exposed Striatal Tissue

Abstract

This study aimed to explore autophagy dynamics and cell death signaling in chronic METH-exposed striatal tissue to elucidate the pathophysiological mechanisms underlying METH-induced neurotoxicity. Utilizing a rodent model of chronic METH exposure, we investigated changes in autophagy-related markers, including LC3-II/I ratio and p62 expression, as well as activation of cell death signaling pathways, such as caspase-3 activation and PARP cleavage, in the striatum. The results demonstrate dysregulated autophagy dynamics characterized by impaired autophagosome formation and accumulation of autophagic substrates in METH-exposed striatal tissue. Moreover, this paper observed the activation of apoptotic signaling cascades, indicating METH-induced neuronal cell death via caspase-mediated pathways. These findings provide novel insights into the molecular mechanisms underlying METH-induced neurotoxicity and highlight the interplay between dysregulated autophagy and apoptotic cell death in the striatum. Understanding these mechanisms may facilitate the development of targeted therapeutic interventions aimed at mitigating the adverse neurological effects of chronic METH use.