Elevated levels of oxidative stress or decreased antioxidant defense mechan
isms may underlie the regionally increased oxidative damage to brain observ
ed in many neurodegenerative disorders. Phase I detoxification pathways for
reactive aldehydes generated from lipid peroxidation include aldehyde dehy
drogenases, alcohol dehydrogenases and aldo-keto reductases (AKR). In the p
resent study, we examined the cellular expression of AKR family member, suc
cinic semialdehyde reductase (AKR7A2) that reduces toxic aldehydes as well
as catalyzing the biosynthesis of the neuromodulator gamma -hydroxybutyrate
(GHB). Our results show that in the cerebral cortex and hippocampus, AKR7A
2 is primarily localized to glial cells, astrocytes and microglia. In the m
idbrain, AKR7A2 was found in glia and neuromelanin-containing neurons of th
e substantia nigra, and the periaqueductal gray. In sections of cerebral co
rtex and hippocampus from patients with AD and DLB, AKR7A2 immunoreactivity
was elevated in reactive astrocytes and microglial cells. Furthermore, tot
al AKR7A2 protein levels were elevated in the cerebral cortex of patients w
ith AD versus control individuals. Our data suggest that reactive gliosis,
as a response to injury, may affect GHB neuromodulatory pathways in neurode
generative disease and elevate aldehyde detoxification pathways. (C) 2001 E
lsevier Science B.V. All rights reserved.