From the, Department of Psychiatry and Behavioral Sciences, (QZ, KMP, EVS, AP, NMZ), Stanford University School of Medicine, Stanford, California.
Neuroscience Program, (KMP, AP, NMZ), SRI International, Menlo Park, California.
Alcohol Clin Exp Res. 2021 Jan;45(1):92-104. doi: 10.1111/acer.14496. Epub 2020 Nov 20.
In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4-day) intragastric ethanol (EtOH) on wild-type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment.
Herein, we used similar voxel-based comparisons of Magnetic Resonance Images collected in EtOH-exposed relative to control animals to test the hypothesis that regardless of the intoxication protocol or the rat strain, the hippocampi, thalami, and colliculi would be affected.
Two experiments [binge (4-day) intragastric EtOH in Fisher 344 rats and chronic (1-month) vaporized EtOH in Wistar rats] showed similarly affected brain regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum. While most of these regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to show response to each proximal EtOH exposure but at diminished levels with repeated cycles.
Given the high metabolic rate of these enduringly affected regions, the current findings suggest that EtOH per se may affect cellular respiration leading to brain volume deficits. Further, responsivity greatly diminished likely reflecting neuroadaptation to repeated alcohol exposure. In summary, this unbiased, in vivo-based approach demonstrating convergent brain systems responsive to 2 EtOH exposure protocols in 2 rat strains highlights regions that warrant further investigation in both animal models of alcoholism and in humans with alcohol use disorder.
在之前一项使用雅可比映射评估 4 天胃内乙醇 binge 对野生型 Wistar 大鼠脑形态影响的研究中,我们报告了丘脑可逆性缩小和侧脑室扩大,但 binge 乙醇处理后仍持续出现上、下丘缩小。
在此,我们使用磁共振成像(MRI)的基于体素比较,比较乙醇暴露动物和对照动物,以检验以下假说:无论中毒方案或大鼠品系如何,海马体、丘脑和丘脑中都会受到影响。
两个实验 [binge(4 天)胃内乙醇暴露 in Fisher 344 大鼠和慢性(1 个月)汽化乙醇暴露 in Wistar 大鼠] 显示了类似的受影响脑区,包括后扣带回皮质和扣带回皮质、背侧海马体、中央和腹后丘脑、上、下丘、中脑导水管周围灰质和胼胝体。虽然这些区域中的大多数显示出显著的恢复,但丘体和中脑导水管周围灰质的体积仍对每次近端乙醇暴露有反应,但在重复周期中反应程度降低。
鉴于这些持久受影响区域的高代谢率,目前的研究结果表明,乙醇本身可能会影响细胞呼吸,导致脑容量不足。此外,反应性大大降低,可能反映了对反复酒精暴露的神经适应。总之,这种基于无偏、体内的方法,在两种大鼠品系的两种乙醇暴露方案中证明了脑系统的一致性,突出了值得在酒精中毒动物模型和有酒精使用障碍的人类中进一步研究的区域。