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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In many areas of the nervous system, excitatory and inhibitory synapses are reconfigured during early development. We have previously described the anatomical refinement of an inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive in the developing gerbil auditory brain stem. Furthermore, these inhibitory synapses display an age-dependent form of long-lasting depression when activated at a low rate, suggesting that this process could support inhibitory synaptic refinement. Since the inhibitory synapses release both glycine and GABA during maturation, we tested whether GABA(B) receptor signaling could initiate the decrease in synaptic strength. When whole cell recordings were made from lateral superior olive neurons in a brain slice preparation, the long-lasting depression of medial nucleus of the trapezoid body-evoked inhibitory potentials was eliminated by the GABA(B) receptor antagonist, SCH-50911. In addition, inhibitory potentials could be depressed by repeated exposure to the GABA(B) receptor agonist, baclofen. Since GABA(B) receptor signaling may not account entirely for inhibitory synaptic depression, we examined the influence of neurotrophin signaling pathways located in the developing superior olive. Bath application of brain-derived neurotrophic factor or neurotrophin-3 depressed evoked inhibitory potentials, and use-dependent depression was blocked by the tyrosine kinase antagonist, K-252a. We suggest that early expression of GABAergic and neurotrophin signaling mediates inhibitory synaptic plasticity, and this mechanism may support the anatomical refinement of inhibitory connections.
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PMID:GABA(B) and Trk receptor signaling mediates long-lasting inhibitory synaptic depression. 1143 32

The present brief review was discussed about the intracellular signal transduction mediated via 5-HT and NA receptors focussing on the mechanism of antidepressants. Recent studies demonstrated that long-term antidepressant treatments resulted in activation of cAMP pathway at several levels including CREB(cAMP response element-binding protein) and BDNF(brain-derived neurotrophic factor). These pathways are elevated via 5-HT and/or NA receptors which directly couple to the cAMP system(5-HT4,6,7 receptors or beta adrenoceptors), or via receptors that lead to activation of Ca(2+)-dependent protein kinase(5-HT2 receptors or alpha 1 adrenoceptors). Such factors could be common targets for many different type of antidepressants. Elucidation of the signal transduction mediated via 5-HT and/or NA receptors, therefore, provide significant information understanding the pathophysiology of depression.
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PMID:[Intracellular signal transduction mediated via 5-HT and NA receptors]. 1151 41

Evidence suggests that brain-derived neurotrophic factor (BDNF) may be important in the pathophysiology of depression, in addition to its role as a neurotrophic factor for sensory neurons. The authors conducted a series of experiments examining the behavioral profile of BDNF heterozygous knockout and wild-type mice. The heterozygous and wild-type mice did not differ on measures of activity, exploration, or hedonic sensitivity, or in the forced swim test. When assessed in the learned helplessness paradigm, heterozygous mice were slower to escape after training than were wild-type mice (p = .02). This effect may be accounted for by the fact that these mice demonstrate a reduced sensitivity to centrally mediated pain, apparent on the hot plate and Formalin injection tests of nociception. Overall, heterozygous mice were not more likely to display anxious or depressive-like behaviors and, consequently, may not constitute a murine model of genetic vulnerability to mood and anxiety disorders.
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PMID:Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. 1158 27

Study of the norepinephrine pathway has elucidated the pathophysiology of depression and bipolar disorder. Various elements along this pathway, including adrenoreceptors, G proteins, cyclic adenosine monophosphate (AMP), cyclic AMP regulatory element binding protein and brain-derived neurotrophic factor, have been identified as potential targets for antidepressants and mood-stabilizing drugs. The results of a wide range of research in this area, along with the hypotheses now under investigation, are summarized in this paper.
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PMID:Postreceptor pathways for signal transduction in depression and bipolar disorder. 1159 Sep 65

An emerging hypothesis suggests that the pathogenesis and treatment of depression is likely to involve a plasticity of neuronal pathways. The inability of neuronal systems to exhibit appropriate, adaptive plasticity could contribute to the pathogenesis of depression. Antidepressant treatments may exert their therapeutic effects by stimulating appropriate adaptive changes in neuronal systems. Recent studies have demonstrated that chronic antidepressant administration up-regulates the cAMP signal transduction cascade resulting in an increased expression and function of the transcription factor CREB. Enhanced CREB expression leads to an up-regulation of specific target genes, including the neurotrophin BDNF. Chronic antidepressant treatments enhance BDNF expression within hippocampal and cortical neurons and can prevent the stress-induced decrease in BDNF expression. Stress has been shown to: (i) induce neuronal atrophy/death; and (ii) decrease neurogenesis of hippocampal neurons. Clinical studies indicate significant hippocampal damage in cases of major, recurrent depression. It is possible that antidepressant treatments through enhanced expression of growth and survival promoting factors like BDNF may prevent or reverse the atrophy and damage of hippocampal neurons. Indeed, studies have indicated that chronic antidepressant treatments enhance hippocampal neurogenesis, promote neuronal sprouting and prevent atrophy. The molecular mechanisms underlying the effects of antidepressant treatments including adaptations in the cAMP transduction cascade, CREB and BDNF gene expression, and structural neuronal plasticity are discussed.
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PMID:Depresssion--emerging insights from neurobiology. 1171 24

We investigated the acute effects of bath applied BDNF on synaptic input to motoneurons in the hemisected spinal cord of the neonatal rat. Motoneurons were recorded intracellularly, and BDNF-induced modulation of the synaptic response to stimulation of the homologous dorsal root (DR) and the ventrolateral funiculus (VLF) was examined. All motoneurons exhibited long-lasting (up to several hours) depression of the DR-activated monosynaptic AMPA/kainate-receptor mediated EPSP in response to BDNF but in about half of the motoneurons this was preceded by facilitation. VLF-evoked AMPA/kainate EPSPs in the same motoneurons were unaffected. BDNF effects were blocked by K252a and were not observed in neonates older than 1 week. Bath applied NMDA antagonists APV and MK-801 abolished both facilitatory and inhibitory actions of BDNF on the AMPA/kainate responses indicating the requirement for functional NMDA receptors. The pharmacologically isolated, DR-evoked, NMDA receptor-mediated response exhibited the same pattern of changes after BDNF superfusion. When introduced into the motoneuron through the recording microelectrode, MK-801 selectively blocked the facilitatory action of BDNF. Furthermore, BDNF enhanced NMDA-induced depolarization of the motoneuron in the presence of tetrodotoxin (TTX), thus, confirming its facilitatory effect on motoneuron NMDA receptors. Bath application of either BDNF or NMDA depressed the monosynaptic EPSP after selective blockade of postsynaptic NMDA receptors indicating a role for presynaptic NMDA receptors in BDNF-induced inhibitory action. Thus, BDNF-induced facilitation of monosynaptic EPSPs in neonatal rats is mediated by direct effects on postsynaptic NMDA receptors, while its inhibitory action occurs presynaptically.
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PMID:Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord. 1186 Apr 75

Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.
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PMID:Decreased serum brain-derived neurotrophic factor levels in major depressed patients. 1192 39

Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.
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PMID:Neurobiology of depression. 1193 38

Previous studies demonstrated that antidepressant treatment increases the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampus. The present study was conducted to test the hypothesis that BDNF in the hippocampus produces an antidepressant effect in behavioral models of depression, the learned helplessness (LH) and forced swim test (FST) paradigms. A single bilateral infusion of BDNF into the dentate gyrus of hippocampus produced an antidepressant effect in both the LH and FST that was comparable in magnitude with repeated systemic administration of a chemical antidepressant. These effects were observed as early as 3 d after a single infusion of BDNF and lasted for at least 10 d. Similar effects were observed with neurotrophin-3 (NT-3) but not nerve growth factor. Infusions of BDNF and NT-3 did not influence locomotor activity or passive avoidance. The results provide further support for the hypothesis that BDNF contributes to the therapeutic action of antidepressant treatment.
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PMID:Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. 1194 26

The neurotrophin (NT) brain-derived neurotrophic factor (BDNF) plays an essential role in the formation of long-term potentiation (LTP). Here, we address whether this modulation by BDNF requires its continuous presence, or whether a local increase in BDNF is necessary during a specific time period of LTP initiation. Using electrical field stimulation of primary cultures of hippocampal neurons, we demonstrate that short high-frequency bursts of stimuli that induce LTP evoke also an instantaneous secretion of BDNF. In contrast, stimuli at low frequencies, inducing long-term depression, do not enhance BDNF secretion, suggesting that BDNF is specifically present, and thus required, at the time of LTP induction. The field-stimulation-mediated BDNF secretion depends on the formation of action potentials and is induced by IP(3)-mediated Ca(2+) release from intracellular stores. Experiments, aimed at determining the sites of NT secretion that use NT6, showed similar patterns of surface labeling by field stimulation to those shown previously by high potassium.
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PMID:Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns. 1198 20


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