Abstract
We recently reported reduced [3H]cyclic adenosine monophosphate binding and catalytic activity of protein kinase
A in prefrontal cortex of depressed suicide victims. Here we examined the molecular
basis of these alterations and whether these findings can be replicated in another
cohort.
Prefrontal cortex from depressed suicide victims and nonpsychiatric controls were
obtained from the Lenhossek Human Brain Program, Budapest and the Maryland Brain Collection
Program. [3H]cyclic adenosine monophosphate binding and protein kinase A activity were determined
by radioligand binding and enzymatic assay, respectively. Expression of catalytic
and regulatory subunits was determined by quantitative reverse transcription polymerase
chain reaction and Western blot, respectively.
[3H]cyclic adenosine monophosphate binding and total and endogenous protein kinase A
activity were significantly decreased in membrane and cytosol fractions of prefrontal
cortex of depressed suicide victims from the Budapest cohort, with a similar magnitude
(33%–40% reduction) as reported for the Maryland cohort. In both cohorts, selective
reduction (36%–41%) in mRNA and protein expression of the regulatory RIIβ and the
catalytic Cβ was observed.
Our results suggest abnormalities in [3H]cyclic adenosine monophosphate binding and catalytic activity kinase A in brain
of depressed suicide victims, which could be due to reduced expression of RIIβ and
Cβ. These abnormalities in PKA may be critical in the pathophysiology of depression.Keywords
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Article info
Publication history
Accepted:
November 5,
2003
Received in revised form:
October 21,
2003
Received:
April 16,
2003
Footnotes
☆Supported by a Career Development Award (KO1 MH 01836) from the National Institute of Mental Health (NIMH) and a Young Investigator Award from the American Foundation for Suicide Prevention to Dr. Yogesh Dwivedi and by RO1 MH48153 from the NIMH to Dr. G.N. Pandey. We acknowledge with thanks the cooperation of John Smialek, M.D., Chief Medical Examiner, and Dennis Chute, M.D., Assistant Medical Examiner, in the collection of brain samples, Ms. Terri U’ Prichard for performing the psychological autopsies, Boris Lapidus, M.D., for the dissections, and Ms. Barbara Brown and Ms. Miljana Petkovich for organizing the brain tissues.
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
