Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence.
Experimenter-delivered alcohol decreases adult hippocampal neurogenesis and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis were observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggest a loss in neuronal turnover and indicate that the hippocampal neurogenic niche is highly vulnerable to alcohol.
Richardson
Heather N
HN
Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA.
Chan
Stephanie H
SH
Crawford
Elena F
EF
Lee
Youn Kyung
YK
Funk
Cindy K
CK
Koob
George F
GF
Mandyam
Chitra D
CD
D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D005452:Fluoresceins; D006624:Hippocampus / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D009930:Organic Chemicals; D017397:Prefrontal Cortex / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration / Q000379:methods
D000089622:Doublecortin Domain Proteins; D005452:Fluoresceins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D009930:Organic Chemicals; C435731:fluoro jade; D000431:Ethanol; D053148:Caspase 3; D001973:Bromodeoxyuridine