The Role of Golgi Morphology in Post-Alcohol Recovery of Hepatocytes: Observations in Cellular and Animal Models

Background: In hepatocytes and alcohol-metabolizing cultured cells, Golgi undergoes ethanol (EtOH)-induced disorganization. Periniclear and organized Golgi is important in liver homeostasis, but how the Golgi remains intact is unknown. Work from our laboratories showed that EtOH-altered cellular function could be reversed after alcohol removal; we wanted to determine whether this recovery would apply to Golgi. Methods: We used alcohol-metabolizing HepG2 (VA-13) cells (cultured with or without EtOH for 72 h) and rat hepatocytes (control and EtOH-fed (Lieber-DeCarli diet). For recovery, EtOH was removed and replenished with control medium (48 hours for VA-13 cells) or control diet (10 days for rats). Results: EtOH-induced Golgi disassembly was associated with de-dimerization of the largest Golgi matrix protein giantin, along with impaired transport of selected hepatic proteins. After recovery from EtOH, Golgi regained their compact structure, and alterations in giantin and protein transport were restored. In VA-13 cells, when we knocked down giantin, Rab6a GTPase or non-muscle Myosin IIB, minimal changes were observed in control conditions, but post-EtOH recovery was impaired. Conclusions: These data provide a link between Golgi organization and plasma membrane protein expression and identify several proteins whose expression is important to maintain Golgi structure during the recovery phase after EtOH administration.

Neuronal effects of experimentally induced hydrocephalus in newborn rats

✓ To determine the effects of increased cerebrospinal fluid (CSF) pressure on neuronal morphology, obstructive hydrocephalus was induced by injecting kaolin into the fourth ventricle and cisterna magna of 1-day-old rats. The animals were sacrificed 10 to 12 days later, at which time severe ventriculomegaly and cortical thinning were apparent in the parieto-occipital region. Tissue from this area was processed by rapid Golgi methods. Well impregnated pyramidal neurons were examined by light microscopy, and their somatic and dendritic features compared to those of age-matched littermate controls. The somata of medium pyramidal neurons were unaffected, but their basilar dendrites had fewer branches and those that remained were shorter. A variable reduction in dendritic spines occurred, such that some branches were totally denuded while others exhibited spine densities similar to those seen in control animals. The most striking alteration was the occurrence of frequent dendritic varicosities. These enlargements of the dendritic shaft separated by extremely thin constrictions gave the affected segment a beaded appearance. Both dendritic spine loss and varicosity formation were most notable on distal portions of individual branches and within regions of the dendritic tree closest to the ventricular and meningeal surfaces. These alterations are consistent with other reports of dendritic changes associated with aging, mental retardation, and alcohol exposure. These observations suggest that hydrocephalus causes dendritic deterioration or retardation of dendritic maturation. The fact that neuronal morphology was not more severely affected may indicate that these effects are reversible.