ReviewA Neurotrophic Model for Stress-Related Mood Disorders
Section snippets
Opposing Actions of Stress and Antidepressant Treatment on BDNF
The time delay for the therapeutic action of antidepressant treatment suggests that adaptations of receptor-coupled signal transduction proteins and their corresponding genes could contribute to the actions of antidepressants. In contrast, alterations in the expression of signaling proteins could also contribute to the effects of stress-related mood disorders. A role for BDNF in the effects of stress and the response to antidepressant treatment is supported by studies demonstrating opposing
BDNF Polymorphisms in Mood Disorders
Based on basic and clinical work on BDNF, recent studies have been undertaken to identify and evaluate BDNF polymorphisms in mood disorders. A functional variant of BDNF at codon 66 (val66met) has been identified with the met allele that results in abnormal intracellular packaging and secretion of BDNF (Egan et al 2003). Carriers of the met allele are reported to have poorer episodic memory and reduced hippocampal N-acetyl aspartate (Egan et al 2003). Studies of the val66met alleles in
Influence of BDNF in Cellular Models of Depression
The regulation of BDNF and other neurotrophic factors by stress and antidepressant treatment could result in alterations at the cellular and behavioral levels. At a cellular level, one of the most interesting areas of research is neurogenesis in the adult hippocampus and the opposing actions of stress and antidepressant treatment. The potential use of neurogenesis as a cellular model for studies of depression and antidepressant response is covered in more detail in another review in this issue.
Influence of BDNF in Behavioral Models of Depression
Studies of adult neurogenesis are useful for identifying cellular actions of antidepressants, but ultimately, it is essential that the behavioral actions of neurotrophic factors are also determined. In this context, the role of BDNF in several established models of depression has been determined. In addition to providing a review of these behavioral data, this section will provide a brief review of the current models of depression/antidepressant response, including the strengths and weaknesses
Limitations of the Neurotrophic Hypothesis
Although there is strong evidence from basic and clinical studies to support a neurotrophic hypothesis of depression, there are also several limitations. Some of the limitations or inconsistencies have been discussed. These include: 1) not all studies report an upregulation of BDNF by antidepressant treatments (Table 1); and 2) not all studies of mutant mice demonstrate a role for BDNF in models of depression. Some of these concerns can be explained by the experimental paradigm used (e.g., dose
Summary
The results of this review support the hypothesis that a reduction of BDNF could contribute to depression and that antidepressants mediate their therapeutic benefit, in part, by increasing levels of this factor in the hippocampus. In addition, the regulation of other neurotrophic/growth factors, including VEGF, IGF-I, and FGF2, may also play a role in the pathophysiology and/or treatment of depression. Two common actions of these different classes of factors are the activation of tyrosine
References (134)
- et al.
The timecourse of induction of brain-derived neurotrophic factor nRNA and protein in the rat hippocampus following voluntary exercise
Neurosci Lett
(2004) - et al.
Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain
Biol Psychiatry
(2003) - et al.
Insulin-like growth factor-I and neurogenesis in the adult mammalian brain
Brain Res Dev Brain Res
(2002) - et al.
Brain-derived neurotrophic factor mRNA downregulation induced by social isolation is blocked by intrahippocampal interleukin-1 receptor anatagonist
Neuroscience
(2003) - et al.
Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication
Biol Psychiatry
(2001) - et al.
Mice with reduced bran-derived neurotrophic factor expression show decreased choline acetyltransferade activity, but regular brain monoamine levels and unaltered emotional behavior
Brain Res Mol Brain Res
(2004) - et al.
Bi-phasic change in BDNF gene expression following antidepressant drug treatment
Neuropharmacology
(2003) - et al.
Assessing antidepressant activity in rodentsRecent developments and future needs
Trends Pharmacol Sci
(2002) - et al.
Fluoxetiine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment
Neuroscience
(2004) - et al.
Differentiation regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain
Neuropharmacology
(2003)
Hippocampal neurogenesisRegulation by stress and antidepressants
Biol Psych
DepressionA case of neuronal life and death?
Biol Psychiatry
The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function
Cell
Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain
Pharmacol Biochem Behav
Regulation of hippocampal neurogenesis in adulthood
Biol Psychiatry
Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder
Biol Psychiatry
Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects
Brain Res
Decreased serum brain-derived neurotrophic factor levels in major depressed patients
Psychol Res
Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs
Brain Res Mol Brain Res
Effect of chronic restraint stress and tianeptine on growth factors, growth-associated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus
Brain Res Mol Brain Res
Hippocampal apoptosis in major depression is a minor event and absent from sub-areas at risk for glucocorticoid overexposure
Am J Pathol
Increased neurogenesis in a model of electro convulsive therapy
Biol Psychiatry
The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain
Mol Cell Neurosci
Effects of adverse experiences for brain structure and function
Biol Psychiatry
Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain
Neuropsychopharmacology
Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder
Neurosci Lett
Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain
Brain Res
Neurobiology of depression
Neuron
The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorderEvidence from a family-based association study
Am J Hum Genet
Repeated stress increases catalytic TrkB mRNA in rat hippocampus
Neurosci Lett
Transport of brain-derived neurotrophic factor across the blood-brain barrier
Neuropharmacology
Acute social defeat reduces neurotrophin expression in brain cortical and susbcortical areas in mice
Brain Res
Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression
Biol Psychiatry
Postnatal repeated maternal deprivation produces age-dependent changes of brain-derived neurotrophic factor expression in selected rat brain regions
Biol Psychiatry
Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression
Neuropsychopharmacology
Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus
Neuroscience
Peripheral infusion of IGF-1 selectively induces neurogenesis in the adult rat hippocampus
J Neurosci
Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways
J Neurosci
The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patientsA preliminary study
Prog Neuropsychopharmacol Biol Psychiatry
Regulation of neurotrophin mRNA expression in the rat brain by glucocorticoids
Eur J Neurosci
Adenoviral brain-derived neurotropohic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain
J Neurosci
The effects of chronic antidepressant treatment in an animal model of anxiety
Psychopharmacology (Berl)
MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder
Am J Psychiatry
Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis
Eur J Neurosci
VEGF links hippocampal activity with neurogenesis, learning and memory
Nat Genet
Is mood chemistry?
Nat Rev Neurosci
Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus
Endocrinology
CREB is essential for the upregulation of BDNF transcription, but not the behavioral or endocrine responses to antidepressant drugs
J Neurosci
Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder
Arch Gen Psychiatry
Use of dopamine-beta-hydroxylase-deficient mice to determine the role of norepinephrine in the mechanism of action of antidepressant drugs
J Pharmacol Exp Ther
Cited by (2796)
Polarization to M1-type microglia in the hippocampus is involved in depression-like behavior in a mouse model of olfactory dysfunction
2024, Neurochemistry InternationalBrain derived neurotrophic factor and treatment outcomes among veterans attending an intensive treatment program for posttraumatic stress disorder
2024, Journal of Psychiatric ResearchSynergistic effects of citicoline and silymarin nanomicelles in restraint stress-exposed mice
2024, Behavioural Brain Research