Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics.
Patients with alcoholism exhibit behavioral adaptations to ethanol such as tolerance, dependence, and addiction. Molecular mechanisms that underlie these altered behavioral responses to ethanol are largely unclear. We have performed oligonucleotide microarray analysis in postmortem prefrontal cortices of alcoholics. Among about 12,000 genes represented on microarray, a total of 79 genes showed differential expression changes in alcoholics compared with control subjects, consisting of 54 up- and 25 down-regulated genes. Altered expressions in alcoholics were observed in genes having a wide range of biological functions. The remarkable findings were up-regulation of myelin-related genes and molecular chaperones in alcoholics. Among the genes identified, decreased expressions of NEFH and PCP4/PEP19 were further examined. NEFH encodes a component of neurofilament protein in neurons. PCP4/PEP19 encodes protein involved in calcium signaling and neuronal apoptosis. Observation of their down-regulations in alcoholics in microarray analysis was confirmed by real-time quantitative RT-PCR, and was also confirmed in the independent set of postmortem brains of alcoholics. The present results may provide some insights into understanding the mechanism of ethanol-induced altered behavioral responses at the molecular level.
Iwamoto
Kazuya
K
Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
Bundo
Miki
M
Yamamoto
Megumi
M
Ozawa
Hiroki
H
Saito
Toshikazu
T
Kato
Tadafumi
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors
D002492:Central Nervous System Depressants; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C050394:PCP4 protein, human; C051774:neurofilament protein H; D000431:Ethanol