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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| Published in: | Biological psychiatry (1969) Vol. 65; no. 4; pp. 319 - 328 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
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New York, NY
Elsevier Inc
15.02.2009
Elsevier |
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| ISSN: | 0006-3223, 1873-2402, 1873-2402 |
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| Abstract | 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. |
|---|---|
| AbstractList | Background The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75NTR ) 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 p75NTR are altered in brain of these subjects. Methods Expression levels of TrkA, B, C, and of p75NTR 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. Results 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 p75NTR 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 p75NTR to Trks were also observed in PFC and hippocampus of suicide subjects. Conclusions Our results suggest not only reduced functioning of Trks in brains of suicide subjects but also that increased ratios of p75NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiology 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 study examines whether expression and activation of Trk receptors and expression of p75(NTR) are altered in brain of these subjects.BACKGROUNDThe 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.METHODSExpression 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.RESULTSIn 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.CONCLUSIONSOur 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. 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. 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. |
| Author | Conley, Robert R. Zhang, Hui Roberts, Rosalinda C. Dwivedi, Yogesh Pandey, Ghanshyam N. Rizavi, Hooriyah S. Mondal, Amal C. |
| AuthorAffiliation | 1 Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor St., Chicago IL, 60612, USA 3 Maryland Psychiatric Research Center, Baltimore, MD, 21201, USA 2 University of Alabama at Birmingham, 865D Sparks Center, 1720 7th Ave South, Birmingham, AL 35294, USA |
| AuthorAffiliation_xml | – name: 1 Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor St., Chicago IL, 60612, USA – name: 3 Maryland Psychiatric Research Center, Baltimore, MD, 21201, USA – name: 2 University of Alabama at Birmingham, 865D Sparks Center, 1720 7th Ave South, Birmingham, AL 35294, USA |
| Author_xml | – sequence: 1 givenname: Yogesh surname: Dwivedi fullname: Dwivedi, Yogesh email: ydwivedi@psych.uic.edu organization: Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago – sequence: 2 givenname: Hooriyah S. surname: Rizavi fullname: Rizavi, Hooriyah S. organization: Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago – sequence: 3 givenname: Hui surname: Zhang fullname: Zhang, Hui organization: Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago – sequence: 4 givenname: Amal C. surname: Mondal fullname: Mondal, Amal C. organization: Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago – sequence: 5 givenname: Rosalinda C. surname: Roberts fullname: Roberts, Rosalinda C. organization: Department of Psychiatry, University of Alabama at Birmingham – sequence: 6 givenname: Robert R. surname: Conley fullname: Conley, Robert R. organization: Maryland Psychiatric Research Center, Baltimore, Maryland – sequence: 7 givenname: Ghanshyam N. surname: Pandey fullname: Pandey, Ghanshyam N. organization: Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago |
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| Keywords | 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 |
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| Snippet | The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75
NTR) and a family of tropomyosin receptor... Background The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75NTR ) and a family of... The physiological functions of neurotrophins occur through binding to two receptors: pan75 neurotrophin receptor (p75(NTR)) and a family of tropomyosin... |
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| SubjectTerms | 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 |
| Title | Neurotrophin Receptor Activation and Expression in Human Postmortem Brain: Effect of Suicide |
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