Suicide brain is associated with decreased expression of neurotrophins

被引:99
作者
Dwivedi, Y
Mondal, AC
Rizavi, HS
Conley, RR
机构
[1] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA
[2] Maryland Psychiat Res Ctr, Baltimore, MD USA
关键词
neurotrophins; suicide; depression; prefrontal cortex; hippocampus; mRNA; ELISA;
D O I
10.1016/j.biopsych.2005.04.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Neurotrophins mediate diverse biological responses, including maintenance and growth of neurons and synaptic plasticity in adult brain. This study examined whether suicide brain is associated with changes in the expression of neurotrophins. Methods. Messenger ribonucleic acid (mRNA) levels of nerve growth factor (NGF), neurotrophin (NT)-3, NT-4/5, and of cyclophilin and neuron-specific enolase (NSE) were measured by quantitative reverse transcriptase polymerase chain reaction, whereas protein levels of neurotrophins were determined by enzyme-linked immunosorbent assay, in prefrontal cortex (PFC) and hippocampus from 28 suicide victims and 21 control subjects. Results: In hippocampus of suicide subjects compared with control subjects mRNA levels of NGF (p <.001), Arf-3 (p <.001), and NT-4/5 (p <.001) were decreased, whether or not they were expressed as a ratio to cyclophilin or NSE. This was accompanied by a decrease in their respective protein levels (NGF [p <.001], AT-3 [p <.001], and AT-4/5 [p <. 0011). In PFC, however, mRNA (p =.001) and protein (p <.001) levels of NT-4/5 and only protein level of NGF (p <.001) were decreased; NT-3 levels were unchanged. Conclusions. Given the role of neurotrophins in synaptic plasticity and maintenance of adult neurons, our findings of altered expression of neurotrophins in postmortem brain of suicide victims suggest that these molecules might play a vital role in the pathophysiology of suicide.
引用
收藏
页码:315 / 324
页数:10
相关论文
共 72 条
[31]   Neurotrophins: Roles in neuronal development and function [J].
Huang, EJ ;
Reichardt, LF .
ANNUAL REVIEW OF NEUROSCIENCE, 2001, 24 :677-736
[32]  
HYMAN C, 1994, J NEUROSCI, V14, P335
[33]  
IANNITELLI A, 1998, GIORN ITAL PSICOPAT, V4, P383
[34]   Decreased serum brain-derived neurotrophic factor levels in major depressed patients [J].
Karege, F ;
Perret, G ;
Bondolfi, G ;
Schwald, M ;
Bertschy, G ;
Aubry, JM .
PSYCHIATRY RESEARCH, 2002, 109 (02) :143-148
[35]  
Klimek V, 1997, J NEUROSCI, V17, P8451
[36]   Physiology of the neurotrophins [J].
Lewin, GR ;
Barde, YA .
ANNUAL REVIEW OF NEUROSCIENCE, 1996, 19 :289-317
[37]   LOCALIZATION AND QUANTIFICATION OF PROOPIOMELANOCORTIN MESSENGER-RNA AND GLUCOCORTICOID RECEPTOR MESSENGER-RNA IN PITUITARIES OF SUICIDE VICTIMS [J].
LOPEZ, JF ;
PALKOVITS, M ;
ARATO, M ;
MANSOUR, A ;
AKIL, H ;
WATSON, SJ .
NEUROENDOCRINOLOGY, 1992, 56 (04) :491-501
[38]   Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis -: Implications for the neurobiology of suicide [J].
López, JF ;
Vázquez, DM ;
Chalmers, DT ;
Watson, SJ .
NEUROBIOLOGY OF SUICIDE: FROM THE BENCH TO THE CLINIC, 1997, 836 :106-134
[39]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[40]   Course of illness, hippocampal function, and hippocampal volume in major depression [J].
MacQueen, GM ;
Campbell, S ;
McEwen, BS ;
MacDonald, K ;
Amano, S ;
Joffe, RT ;
Nahmias, C ;
Young, LT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (03) :1387-1392