Glutamate signaling proteins and tyrosine hydroxylase in the locus coeruleus of alcoholics.
It has been postulated that alcoholism is associated with abnormalities in glutamatergic neurotransmission. This study examined the density of glutamate NMDA receptor subunits and its associated proteins in the noradrenergic locus coeruleus (LC) in deceased alcoholic subjects. Our previous research indicated that the NMDA receptor in the human LC is composed of obligatory NR1 and regulatory NR2C subunits. At synapses, NMDA receptors are stabilized through interactions with postsynaptic density protein (PSD-95). PSD-95 provides structural and functional coupling of the NMDA receptor with neuronal nitric oxide synthase (nNOS), an intracellular mediator of NMDA receptor activation. LC tissue was obtained from 10 alcohol-dependent subjects and eight psychiatrically healthy controls. Concentrations of NR1 and NR2C subunits, as well as PSD-95 and nNOS, were measured using Western blotting. In addition, we have examined tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of norepinephrine. The amount of NR1 was lower in the rostral (-30%) and middle (-41%) portions of the LC of alcoholics as compared to control subjects. No differences in the amounts of NR2C, PSD-95, nNOS and TH were detected comparing alcoholic to control subjects. Lower levels of NR1 subunit of the NMDA receptor in the LC implicates altered glutamate-norepinephrine interactions in alcoholism.
Karolewicz
Beata
B
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, USA.
Johnson
Laurel
L
Szebeni
Katalin
K
Stockmeier
Craig A
CA
Ordway
Gregory A
GA
D000328:Adult; D000437:Alcoholism / Q000175:diagnosis* / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005971:Glutamates / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D008125:Locus Coeruleus / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism*
D002352:Carrier Proteins; C485668:GRIN1 protein, human; D005971:Glutamates; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase