Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects.
BACKGROUND
Suicide is a major public health concern. Although authors of many studies have examined the neurobiological aspects of suicide, the molecular mechanisms associated with suicidal behavior remain unclear. Brain-derived neurotrophic factor (BDNF), one of the most important neurotrophins, after binding with and activating receptor tyrosine kinase B (trk B), is directly involved in many physiological functions in the brain, including cell survival and synaptic plasticity. The present study was performed to examine whether the expression of BDNF and/or trk B isoforms was altered in postmortem brain in subjects who commit suicide (hereafter referred to as suicide subjects) and whether these alterations were associated with specific psychopathologic conditions.


METHODS
These studies were performed in prefrontal cortex in Brodmann area 9 and hippocampus obtained in 27 suicide subjects and 21 nonpsychiatric control subjects. Levels of messenger RNA and protein levels of BDNF and trk B were determined with competitive reverse transcriptase-polymerase chain reaction and Western blot technique, respectively. The level of neuron-specific enolase messenger RNA as a neuronal marker was also determined in these brain areas.


RESULTS
Messenger RNA levels of BDNF and trk B were significantly reduced, independently and as a ratio to neuron-specific enolase, in both prefrontal cortex and hippocampus in suicide subjects, as compared with those in control subjects. These reductions were associated with significant decreases in the protein levels of BDNF and of full-length trk B but not trk B's truncated isoform. These changes were present in all suicide subjects regardless of psychiatric diagnosis and were unrelated to postmortem interval, age, sex, or pH of the brain.


CONCLUSIONS
Given the importance of BDNF in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF and trk B in postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.
Dwivedi
Yogesh
Y
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 60612, USA. ydwivedi@psych.uic.edu
Rizavi
Hooriyah S
HS
Conley
Robert R
RR
Roberts
Rosalinda C
RC
Tamminga
Carol A
CA
Pandey
Ghanshyam N
GN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002423:Cause of Death; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008396:Maryland; D001523:Mental Disorders / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D017397:Prefrontal Cortex / Q000473:pathology*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020813:Receptor, trkB / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013405:Suicide
D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D020813:Receptor, trkB; D010751:Phosphopyruvate Hydratase