Cigarette smoke exposure has region-specific effects on GDAP1 expression in mouse hippocampus

Abstract

Early detection markers for substance use disorders are urgently needed. Recently, an association between the methylation of Ganglioside-induced differentiation-associated protein 1 (GDAP1) and alcohol addiction was found in a US and German population. In this study, we investigate whether GDAP1 expression might be affected by cigarette smoke as well and thus might be a marker of substance addiction in general. 11 adult female C57BL/6 J mice (6 wildtype and 5 lacking the NO-sensitive guanylyl cyclase1 (NO-GC1 KO)) were exposed to cigarette smoke over a period of 5 weeks, their brains immunohistochemically stained and compared to 11 non exposed mice (5 WT and 6 KO). The deletion of NO-GC1 results in a complete loss of synaptic plasticity, therefore, addiction-related alterations might become more obvious. Co-staining of anti-GDAP1 and DAPI revealed protein in the stratum granulare of the hippocampus. Three randomized frames for dentate gyrus (DG) and three for Cornu Ammonis region 1 (CA1) were used to count GDAP1. Cigarette smoke exposure significantly influenced GDAP1 expression depending on the hippocampal region but was not influenced by guanyl cyclase. In conclusion, cigarette smoke exposure alone had an effect on GDAP1 amount in both regions. Therewith, GDAP1might be a biomarker for substance addiction in general.

Keywords: CA1; Dentate gyrus; Immunohistochemistry; Mouse model; Nicotinic acetylcholine receptors.