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dc.contributor.authorAgis Balboa, Roberto Carlos 
dc.contributor.authorGuidotti, Alessandro
dc.contributor.authorPinna, Graziano
dc.date.accessioned2017-06-07T06:58:52Z
dc.date.available2017-06-07T06:58:52Z
dc.date.issued2014
dc.identifier.issn0033-3158
dc.identifier.urihttp://hdl.handle.net/20.500.11940/1297
dc.description.abstractRATIONALE: The implications of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one [allopregnanolone (Allo)] in neuropsychiatric disorders have been highlighted in several recent clinical investigations. For instance, Allo levels are decreased in the cerebrospinal fluid (CSF) of patients with posttraumatic stress disorder (PTSD) and major unipolar depression. Neurosteroidogenic antidepressants [i.e., selective brain steroidogenic stimulants (SBSSs)], including fluoxetine and analogs, correct this decrease in a manner that correlates with improved depressive symptoms. Allo positively and allosterically modulates GABA action at postsynaptic and extrasynaptic GABAA receptors. It is synthesized in both the human and rodent brain cortices by principal glutamatergic pyramidal neurons from progesterone by the sequential action of 5alpha-reductase type I (5alpha-RI), which is the rate-limiting step enzyme in Allo biosynthesis, and 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), which converts 5alpha-dehydroprogesterone into Allo. HYPOTHESIS: We thus hypothesized that decreased CSF levels of Allo in depressed patients could reflect a brain dysfunction of 5alpha-RI. METHODS: In a pilot study of samples from six patients per group [six depressed patients and six nonpsychiatric subjects (NPS)], we studied the expression of 5alpha-RI messenger RNA (mRNA) in prefrontal cortex Brodmann's area 9 (BA9) and cerebellum from depressed patients obtained from the Maryland Brain Collection at the Maryland Psychiatric Research Center (Baltimore, MD) that were age-matched with NPS. RESULTS: The levels of 5alpha-RI mRNA were decreased from 25 +/- 5.8 in NPS to 9.1 +/- 3.1 fmol/pmol neuronal specific enolase (NSE) (t1,10 = 2.7, P = 0.02) in depressed patients. These differences are absent in the cerebellum of the same p
dc.language.isoeng
dc.subject.meshAdult
dc.subject.meshDepressive Disorder, Major
dc.subject.meshDown-Regulation
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPilot Projects
dc.subject.meshPrefrontal Cortex
dc.subject.meshPyramidal Cells
dc.subject.meshRNA, Messenger
dc.subject.meshSuicide
dc.subject.meshTissue Banks
dc.subject.meshYoung Adult
dc.title5alpha-reductase type I expression is downregulated in the prefrontal cortex/Brodmann's area 9 (BA9) of depressed patients.
dc.typeArtigo
dc.authorsophosAgis-Balboa, Roberto Carlos
dc.authorsophosGuidotti, Alessandro
dc.authorsophosPinna, Graziano;
dc.identifier.doi10.1007/s00213-014-3567-5
dc.identifier.isi340684300029
dc.identifier.pmid24781515
dc.identifier.sophos17485
dc.issue.number17
dc.journal.titlePSYCHOPHARMACOLOGY
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Vigo::IBI - Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number231


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