What may be surprising is that pathways related to neuronal development and connectivity appear to be activated, with most genes in axonal guidance and synaptogenesis pathways increased in expression. The cholesterol biosynthesis pathway was decreased. TP53-controlled genes included some affecting the cell cycle, which may indicate that cell cycle were being slowed by checkpoint mechanisms. Stress systems like the unfolded protein response were activated; NFκB1 expression is increased and genes downstream of NFκB were affected. Another surprising finding was that the many changes evoked by the CIE exposure over 3 weeks returned nearly to baseline after only 24 h of withdrawal. It is possible that more lasting changes could result from exposures over a much longer period, or that chronic heavy exposure of individuals might lead to changes in connectivity within the brain, or might predispose to stronger effects of ethanol on reexposure.
