Altered Oligodendroglial and Neuroglial Gene Expression in Adult Rat Cerebral White Matter Following Short- and Long-Term Ethanol Exposures and Abbreviated Abstinence

Ethanol-mediated white matter degeneration is associated with impaired oligodendrocyte functions linked to myelin maintenance. This study examines ethanol-induced time course-dependent shifts in myelin gene expression in a chronic+binge exposure model and assesses therapeutic responses to short-term abstinence. Six-week-old male Long Evans rats were fed isocaloric liquid diets with 0% or 26% ethanol (caloric content) for 3 or 8 weeks. During the last 2 weeks of ethanol feeding, the rats were binged with 2 g/kg ethanol by intraperitoneal injection, 3x/week. In a subgroup pair-fed for 6 weeks, ethanol was tapered over 2 days and then withdrawn for 12 days. Gene expression in temporal lobe white matter was measured by qRT-PCR analysis. Chronic+binge ethanol exposures caused short-term, long-term, or step-wise changes in neuroglial gene expression such that: 1) NCAM1 mRNA levels were significantly elevated after 3 weeks (P=0.04); 2) PLP was reduced after 8 weeks (P=0.003); and 3) MAG (P=0.008) and RTN4 (P=0.02) progressively declined from 3 to 8 weeks of exposure. Abstinence did not reverse long-term ethanol effects on PLP, MAG or RTN4. Instead, it significantly reduced RPAIN (P=0.002) and Olig2 (P=0.02) relative to responses after 8 weeks of continuous ethanol exposure. In conclusion, chronic+binge ethanol exposures mainly inhibited mature myelin-associated gene expression. Short-term abstinence failed to abrogate those adverse effects of ethanol. Instead, the corresponding reductions in RPAIN and Olig2 expression suggest that during the acute phase of withdrawal or abstinence, molecular indices of white matter degeneration may worsen and that additional therapeutic measures may be required for optimum recovery.