Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression.

Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2002; 22(8):3251-61. DOI: 10.3410/f.1005737.68355
Source: PubMed


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.

20 Reads
    • "BDNF regulates synaptic neuronal survival and peripheral and central neuroplasticity (Binder and Scharfman 2004). It has been studied in pathological conditions such as depression and chronic pain (Hu and Russek 2008; Shirayama et al. 2002). In healthy subjects, the modulating effect of BDNF on the nervous system is gender dependent (Stefani et al. 2012). "

    Life sciences 10/2015; DOI:10.1016/j.lfs.2015.10.011 · 2.70 Impact Factor
  • Source
    • "Conversely, antidepressants, including the atypical antidepressant ketamine , have been shown to enhance BDNF production, or even transactivate the BDNF-TrkB (tropomyosin receptor kinase B) receptor, thereby counteracting depressionassociated BDNF-TrkB downregulation (Lindholm and Castrén, 2014). That antidepressants could act through supraspinal BDNF-TrkB activation is supported by data showing that direct intracerebral administration of BDNF itself exerts antidepressant-like effects in validated rodent models of depression (Shirayama et al., 2002). However, it would be irrelevant to infer that an upregulation of BDNF always contributes to an antidepressant action because direct injection of BDNF into the ventral tegmental area was found to cause depression-like behavior, whereas BDNF signaling blockade in the nucleus accumbens produced antidepressant-like effects (Berton et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague-Dawley male rats were either injected intrathecally with BDNF (3.0ng i.t.) or subjected to unilateral CCI-SN. Their respective responses to anti-hyperalgesic drugs were assessed using the Randall-Selitto test and both immunohistochemical and RT-qPCR approaches were used to investigate molecular/cellular mechanisms underlying hyperalgesia in both models. Long lasting hyperalgesia and allodynia were induced by i.t. BDNF in intact healthy rats like those found after CCI-SN. Acute treatment with the BDNF-TrkB receptor antagonist cyclotraxin B completely prevented i.t. BDNF-induced hyperalgesia and partially reversed this symptom in both BDNF-pretreated and CCI-SN lesioned rats. Acute administration of the anticonvulsant pregabalin, the NMDA receptor antagonist ketamine, the opioid analgesics morphine and tapentadol or the antidepressant agomelatine also transiently reversed hyperalgesia in both i.t. BDNF injected- and CCI-SN lesioned-rats. Marked induction of microglia activation markers (OX42, Iba1, P-p38), proinflammatory cytokine IL-6, NMDA receptor subunit NR2B and BDNF was found in spinal cord and/or dorsal root ganglia of CCI-SN rats. A long lasting spinal BDNF overexpression was also observed in BDNF i.t. rats, indicating an autocrine self-induction, with downstream long lasting TrkB-mediated neuropathic-like pain. Accordingly, TrkB blockade appeared as a relevant approach to alleviate not only i.t. BDNF- but also nerve lesion-evoked neuropathic pain.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 09/2015; 25(11). DOI:10.1016/j.euroneuro.2015.07.026 · 4.37 Impact Factor
    • "Brain-derived neurotrophic factor (BDNF) is a well-studied neurotrophin directly implicated in the pathophysiology of MD and in the mechanism of action of antidepressants. Intra-hippocampal injection or viral overexpression of BDNF produce antidepressant effects in animal models for depression [4] [5] [6] [7], while reducing BDNF by means of RNA interference in the DG or by a conditional BDNF deletion in the forebrain attenuates antidepressant efficacy [8] [9]. A conditional knock-out of BDNF in the forebrain induces depressionlike behavior in female mice [8], and local silencing of BDNF in the dorsal DG in male rats increases anhedonia and despair [10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Brain-derived neurotrophic factor (BDNF) exerts antidepressant-like effects in the hippocampus and pro-depressant effects in the nucleus accumbens (NAc). It is thought that downstream signaling of the BDNF receptor TrkB mediates the effects of BDNF in these brain structures. Here, we evaluate how TrkB regulates affective behavior in the hippocampus and NAc. We overexpressed TrkB by electroporating a non-viral plasmid in the NAc or hippocampus in mice. Depression- and anxiety-like behaviors were evaluated in the sucrose test (anhedonia), the forced swim test (despair) and the elevated zero maze (anxiety). Targeted brain tissue was biochemically analyzed to identify molecular mechanisms responsible for the observed behavior. Overexpressing TrkB in the NAc increased the number of young neuronal cells and decreased despair and basal corticosterone levels. TrkB overexpression in the hippocampus increased astrocyte production and activation of the transcription factor CREB, yet without altering affective behavior. Our data suggest antidepressant effects of BDNF-TrkB in the NAc, which could not be explained by activation of the transcription factors CREB or β-catenin. The effects TrkB has on depression-related behavior in different brain regions appear to critically depend on the targeted cell type.
    Behavioural brain research 08/2015; 296. DOI:10.1016/j.bbr.2015.08.027 · 3.03 Impact Factor
Show more

Preview (2 Sources)

20 Reads
Available from