The distributions of class III alcohol dehydrogenase (ADH), a glutathione-d
ependent formaldehyde dehydrogenase, and class I ADH in the human brain wer
e examined immunohistochemically. The most intense immunostaining of class
III ADH was observed in the dendrites and cytoplasm of cerebellar Purkinje
cells. Scattered cerebral cortical neurons in layers IV and V, and some hip
pocampal pyramidal neurons were also immunopositive. The neuronal distribut
ion of class III ADH resembled that of the vulnerable neurons in patients w
ith hypoxic encephalopathy, which in view of the intense staining in the Pu
rkinje cells, raises the possibility that this enzyme contributes to the hy
poxia and cerebellar degeneration suffered by chronic alcoholics, Perivascu
lar and subependymal astrocytes, which contribute to the maintenance of the
cerebral cellular milieu and isolate the brain from the systemic circulati
on and cerebrospinal fluid, were also class III ADH positive. As the substr
ates of this enzyme include intrinsic toxic formaldehyde, inflammatory inte
rmediate of 20-hydroxy-leukoteiene B4, and possibly ethanol, the distributi
on of class III ADH immunostaining indicates this enzyme contributes to the
defence of the brain against degenerative processes. The finding that, unl
ike ependymal cells, subependymal astrocytes were class III ADH positive, s
uggests this enzyme may be useful for differentiating astrocytes and ependy
mal cells. (C) 2000 Elsevier Science B.V. All rights reserved.