Neurotrophin Receptor Activation and Expression in Human Postmortem Brain: Effect of Suicide

The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75 NTR) and a family of tropomyosin receptor kinases (Trks A, B, and C). We recently reported that expression of neurotrophins and TrkB were reduced in brains of suicide subjects. This...

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Veröffentlicht in:Biological psychiatry (1969) Jg. 65; H. 4; S. 319 - 328
Hauptverfasser: Dwivedi, Yogesh, Rizavi, Hooriyah S., Zhang, Hui, Mondal, Amal C., Roberts, Rosalinda C., Conley, Robert R., Pandey, Ghanshyam N.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York, NY Elsevier Inc 15.02.2009
Elsevier
Schlagworte:
Adult and adolescent clinical studies
Antidepressive Agents - poisoning
Antidepressive Agents - therapeutic use
Biological and medical sciences
Blotting, Western
Brain Chemistry - physiology
Depression
Depressive Disorder, Major - metabolism
gene expression
Hippocampus - metabolism
Humans
Immunoprecipitation
Medical sciences
Mood disorders
p75 NTR
Phosphorylation
Phosphotyrosine - metabolism
postmortem brain
Prefrontal Cortex - metabolism
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptor, Nerve Growth Factor - biosynthesis
Receptor, Nerve Growth Factor - genetics
Receptor, trkA - biosynthesis
Receptor, trkA - genetics
Receptor, trkB - biosynthesis
Receptor, trkB - genetics
Receptor, trkC - biosynthesis
Receptor, trkC - genetics
Receptors, Nerve Growth Factor - biosynthesis
Receptors, Nerve Growth Factor - physiology
RNA, Complementary - biosynthesis
RNA, Complementary - genetics
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Suicide
Trk
Depression
postmortem brain
Trk
p75 NTR
gene expression
suicide
Mood disorder
Human
Neurotrophin
p75NTR
suicide,Trk
Central nervous system
Postmortem
Activation
Gene expression
Suicide
Genetic determinism
Encephalon
Genetics
Biological receptor
ISSN:0006-3223, 1873-2402, 1873-2402
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Zusammenfassung:The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75 NTR) and a family of tropomyosin receptor kinases (Trks A, B, and C). We recently reported that expression of neurotrophins and TrkB were reduced in brains of suicide subjects. This study examines whether expression and activation of Trk receptors and expression of p75 NTR are altered in brain of these subjects. Expression levels of TrkA, B, C, and of p75 NTR were measured by quantitative reverse transcription polymerase chain reaction and Western blot in prefrontal cortex (PFC) and hippocampus of suicide and normal control subjects. The activation of Trks was determined by immunoprecipitation followed by Western blotting using phosphotyrosine antibody. In hippocampus, lower mRNA levels of TrkA and TrkC were observed in suicide subjects. In the PFC, the mRNA level of TrkA was decreased, without any change in TrkC. However, the mRNA level of p75 NTR was increased in both PFC and hippocampus. Immunolabeling studies showed similar results as observed for the mRNAs. In addition, phosphorylation of all Trks was decreased in hippocampus, but in PFC, decreased phosphorylation was noted only for TrkA and B. Increased expression ratios of p75 NTR to Trks were also observed in PFC and hippocampus of suicide subjects. Our results suggest not only reduced functioning of Trks in brains of suicide subjects but also that increased ratios of p75 NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiology of suicide.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0006-3223
1873-2402
1873-2402
DOI:10.1016/j.biopsych.2008.08.035