Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims.
The development of new therapies for the treatment of psychiatric disorders requires an in-depth knowledge of the molecular bases underlying these pathologies, which remain largely unknown. Alterations in adrenoceptors, serotonin receptors, and other G protein-coupled receptors (GPCRs) have been associated with suicide and depression. However, to date, there is little information about mRNA expression of the GPCRs in the frontal cortex of suicide victims. Our goal was to study the expression in the brain of these receptors. For this purpose, we measured mRNA levels by RT-PCR. We found that the expressions of alpha2A-adrenoceptors, 5-HT1A, 5-HT2A serotonin receptors, and mu-opioid receptors were elevated in the post-mortem brains of these suicide victims with respect to matched controls. Moreover, in the case of alpha2A-adrenoceptors (the only for which these data were available), a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of this receptor was not influenced by post-translational regulatory mechanisms. In addition, the degree of adrenoceptor and 5-HT receptor expressions appeared to be correlated in the brains of suicide victims and control subjects. Alterations in the expression of adrenoceptors, serotonin, and opioid receptors indicate that these signaling proteins might be related to the etiopathology of suicidal and depressive behaviors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. The results also suggest that these receptors could share common regulatory mechanisms.
Escribá
Pablo V
PV
Laboratory of Neuropharmacology, Associated Unit of the Cajal Institute (CSIC), Department of Biology, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba.uib.es
Ozaita
Andrés
A
García-Sevilla
Jesús A
JA
D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis* / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000096:biosynthesis* / Q000235:genetics; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013405:Suicide
C547768:ADRA2A protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin