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), NT-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], NT-3 [p < .001], and NT-4/5 [p
< .001]). 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.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effects of NT-4, BDNF, or NGF on the survival and phenotypic differentiation of septal cholinergic neurons in long-term cultures.Soc Neurosci Abstr. 1993; 19: 666
- Neurotrophin-4/5 selectively protects nigral calbindin-containing neurons in rats with medial forebrain bundle transections.Neuroscience. 1996; 72: 911-921
- Identification of genes regulated by chronic psychosocial stress and antidepressant treatment in the hippocampus.Eur J Neurosci. 2004; 19: 659-666
- The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic systems during behaviorally effective infusions to the substantia nigra.Exp Neurol. 1994; 130: 31-40
- The hippocampus and parahippocampus in schizophrenia, suicide, and control brains.Arch Gen Psychiatry. 1990; 47: 1029-1034
- Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression.Neuroreport. 2000; 11: 1369-1373
- Autoradiographic demonstration of increased serotonin 5HT2 and β-adrenergic receptor binding sites in the brain of suicide victims.Arch Gen Psychiatry. 1990; 47: 1038-1047
- Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims.Brain Res. 1995; 688: 121-133
- Fewer pigmented locus coeruleus neurons in suicide victims.Biol Psychiatry. 1996; 39: 112-120
- Elevated CSF CRF in suicide victims.Biol Psychiatry. 1989; 25: 355-359
- Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo.Nature. 1994; 367: 368-371
- Neurotrophic factors and their receptors.Curr Opin Cell Biol. 1995; 7: 148-155
- Data and hypotheses on the role of nerve growth factor and other neurotrophins in psychiatric disorders.Med Hypotheses. 2000; 55: 199-207
- Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims.Synapse. 1992; 10: 79-82
- Noradrenergic neurons in locus coeruleus.Soc Neurosci Abstr. 1993; 19: 1101
- Nerve growth factor.Stroke. 1990; 21: 177
- Suicide.Psychiatr Clin North Am. 1985; 8: 203-214
- Delayed death of septal cholinergic neurons after excitotoxic ablation of hippocampal neurons during early postnatal development in the rat.Exp Neurol. 1996; 139: 143-155
- Expression of calcium-binding proteins in the neurotrophin-3-dependent subpopulation of rat embryonic dorsal root ganglion cells in culture.Brain Res Dev Brain Res. 1994; 81: 57-65
- Structural abnormalities in depression.CNS Spectrum. 2002; 7: 140-147
- Depression.Biol Psychiatry. 2004; 56: 140-145
- Neuronal plasticity and survival in mood disorders.Biol Psychiatry. 2000; 48: 732-739
- Neurotrophic factors and the pathophysiology of schizophrenic psychoses.Eur Psychiatry. 2004; 19: 326-337
- Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects.Arch Gen Psychiatry. 2003; 60: 273-282
- Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects.Arch Gen Psychiatry. 2003; 60: 804-815
- Differential actions of neurotrophins in the locus coeruleus and basal forebrain.Exp Neurol. 1993; 119: 72-78
- Prefrontal cortex dysfunction in clinical depression.Depression. 1994; 2: 59-72
- Regulation of hippocampal neurogenesis in adulthood.Biol Psychiatry. 2000; 48: 715-720
- The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies.Neurosci Lett. 1995; 200: 151-154
- Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls.Mol Psychiatry. 2001; 6: 540-546
- Neurotrophins.Annu Rev Neurosci. 2001; 24: 677-736
- Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon.J Neurosci. 1994; 14: 335-347
- Dati acquisiti ed ipotesi emergenti sul ruolo delle neurotrofine, in particolare dell’NGF, in patologie di natura psichiatrica.Giorn Ital Psicopat. 1998; 4: 383-392
- Decreased serum brain-derived neurotrophic factor levels in major depressed patients.Psychiatry Res. 2002; 109: 143-148
- Reduced levels of norepinephrine transporters in the locus coeruleus in major depression.J Neurosci. 1997; 17: 8451-8458
- Physiology of the neurotrophins.Annu Rev Neurosci. 1996; 19: 289-317
- Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims.Neuroendocrinology. 1992; 56: 491-501
- Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis.Implications for the neurobiology of suicide. Ann N Y Acad Sci. 1997; 836: 106-134
- Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 193: 266-275
- Course of illness, hippocampal function, and hippocampal volume in major depression.Proc Natl Acad Sci U S A. 2003; 100: 1387-1392
- Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain.J Neurosci. 1995; 15: 7929-7939
- The neurobiology of suicide.Nat Med. 1998; 4: 25-30
- Increased serotonin2 and β-adrenergic receptor binding in the frontal cortices of suicide victims.Arch Gen Psychiatry. 1986; 43: 954-959
- Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors.J Neurosci. 1994; 14: 1262-1270
- Neurotrophins and neuronal differentiation in the central nervous system.Cell Mol Life Sci. 2001; 58: 1054-1060
- Neurotrophins and synaptic plasticity.Annu Rev Neurosci. 1999; 22: 295-318
- Stress and hippocampal plasticity.Annu Rev Neurosci. 1999; 22: 105-122
- Morphological brain changes in depression.CNS Drugs. 2002; 16: 361-372
- Epidemiology of suicide.Epidemiol Rev. 1987; 9: 51-69
- Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims.Arch Gen Psychiatry. 1988; 45: 577-579
- Higher expression of serotonin 5HT2A receptors in the postmortem brains of teenage suicide victims.Am J Psychiatry. 2002; 159: 419-429
- Expression of nerve growth factor and neurotrophin-3 mRNAs in hippocampal interneurons.J Comp Neurol. 1998; 365: 73-90
- Neurotrophins as synaptic modulators.Nat Rev Neurosci. 2001; 2: 24-32
- Rapid and opposite effects of BDNF and NGF on the functional organization of the adult cortex in vivo.Nature. 1996; 381: 702-706
- Morphometric methods for studying the prefrontal cortex in suicide victims and psychiatric patients.Ann N Y Acad Sci. 1997; 836: 253-268
- Histopathology of the prefrontal cortex in major depression.Prog Brain Res. 2000; 126: 397-412
- Stress and hippocampal abnormalities in psychiatric disorders.Eur Neuropsychopharmacol. 2004; 14: 393-405
- Stress, glucocorticoids, and damage to the nervous system.Stress. 1996; 1: 1-19
- The possibility of neurotoxicity in the hippocampus in major depression.Biol Psychiatry. 2000; 48: 755-765
- Nerve growth factor brain concentration and stress.Int Dev Neurosci. 2000; 18: 469-479
- Untreated depression and hippocampal volume loss.Am J Psychiatry. 2003; 160: 1516-1518
- Amelioration of delayed neuronal death in the hippocampus by nerve growth factor.J Neurosci. 1991; 11: 2914-2919
- Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.Biol Psychiatry. 2003; 54: 70-75
- Calcium-binding protein (calbindin-D28K) and paravalbumin immunocytochemistry.J Comp Neurol. 1989; 280: 183-196
- Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNA in the hippocampus.J Neurosci. 1995; 15: 1768-1777
- Survival of adult basal cholinergic neurons after loss of target neurons.Science. 1990; 247: 338-342
- Prefrontal abnormality of schizophrenia revealed by DNA microarray.Ann N Y Acad Sci. 2004; 1025: 84-91
- Hippocampal function in cognition.Psychopharmacology. 2004; 174: 99-110
- The changing scene of neurotrophic factors.Trends Neurosci. 1991; 14: 165-170
- Neurotrophins and activity-dependent plasticity.Prog Brain Res. 2000; 128: 183-191
- Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain.Neurosci Res. 1997; 28: 103-110
- Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons.Brain Res. 1990; 531: 225-231
Article info
Publication history
Published online: June 06, 2005
Accepted:
April 12,
2005
Received in revised form:
April 11,
2005
Received:
December 6,
2004
Footnotes
This work was supported by grant RO1MH68777 from the National Institute of Mental Health, a Career Development Award (KO1MH 01836) from the National Institute of Mental Health, and a Young Investigator Award from the American Foundation for Suicide Prevention to YD.
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.