ICAM5如何调节酒精依赖？海马过表达模型的神经保护机制解析

Alcohol dependence, also known as alcohol use disorder, is a complex chronic relapsing brain disease characterized by a strong craving for alcohol, loss of control over drinking behavior, and tolerance and withdrawal reactions to alcohol. Alcohol dependence not only poses a serious threat to human health but also imposes a heavy socioeconomic burden, making it an urgent public health issue. Chronic alcohol exposure can lead to the remodeling of brain reward and neuroregulatory pathways, causing pathological damage in multiple brain regions, including the prefrontal cortex, hippocampus, cerebellum, and amygdala. This damage is primarily associated with changes in neurotransmitter release and synaptic plasticity, with the hippocampus, a key brain region involved in drug addiction memory and relapse behavior, being the most extensively studied. Intercellular adhesion molecule 5 (ICAM5), also known as telencephalin, is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily, specifically expressed in mammalian telencephalic neurons (particularly in the dendrites and cell bodies of excitatory neurons). ICAM5 can regulate neuronal signaling by modulating synaptic plasticity and also functions as an immune regulatory factor, participating in the bidirectional regulation of neuroinflammation, thereby potentially offering neuroprotective effects. However, the mechanisms by which ICAM5 contributes to the pathophysiology of alcohol addiction remain unclear. Our previous research has shown that ICAM5 can modulate the structural plasticity of dendritic spines in hippocampal neurons of alcohol-dependent mice. Building on this, we used a two-bottle choice drinking mouse model to investigate the effects of hippocampal overexpression of ICAM5 on mice's alcohol preference, learning and memory abilities, and motor balance, and to explore the potential molecular mechanisms. This study aims to provide new experimental evidence for the mechanisms underlying alcohol addiction and to identify potential therapeutic targets for alcohol withdrawal.