Disease relevance of Bdnf

• BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease [1].
• PNT-1 also promoted survival of a greater number of embryonic dorsal root ganglion neurons than any of the other neurotrophins alone, and its effects were equivalent to a combination of NGF, BDNF, and NT-3 [2].
• BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period [3].
• Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3'-kinase pathway [4].
• Ischemia and reperfusion increased hippocampal levels of BDNF [5].

Psychiatry related information on Bdnf

• Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations [3].
• Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease [6].
• In parallel studies, we observed a higher level of BDNF in EDL muscle during the critical period of development when motor neurons are highly susceptible to target removal [7].
• Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats [8].
• 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 [9].

High impact information on Bdnf

• Thus trkB encodes an essential component of a functional receptor for BDNF and NT-3, but not for NGF [10].
• BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization [11].
• A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely, is released on neuron depolarization, and triggers rapid intracellular signals and action potentials in central neurons [11].
• Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens both during development and in adulthood [11].
• We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration [12].

Chemical compound and disease context of Bdnf

• Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF [5].
• Finally, with the accumulating evidence linking BDNF to synaptic plasticity, we investigated whether BDNF-induced hyperalgesia in normal mice involves the N-methyl-D-aspartate (NMDA) receptor [13].
• Brain-derived neurotrophic factor (BDNF) promotes the survival of dopamine (DA) neurons, enhances expression of DA neuron characteristics, and protects these cells from 6-hydroxydopamine (6-OHDA) toxicity in vitro [14].
• Peripheral inflammation increases expression of BDNF preferentially in dorsal root ganglion cells that contain substance P and/or calcitonin gene-related peptide, known nociceptive transmitters for which synthesis is also increased during inflammatory states [13].
• Involvement of the brain-derived neurotrophic factor/TrkB pathway in neuroprotecive effect of cyclosporin A in forebrain ischemia [15].

Biological context of Bdnf

• Bdnf mRNA showed transient up-regulation after 2 and 5 h of reperfusion and remained at control levels thereafter [16].
• Grafting of P3 hypothyroid rats with cell lines expressing high levels of neurotrophin 3 (NT-3) or BDNF prevented hypothyroidism-induced cell death in neurons of the internal granule cell layer at P15 [17].
• Furthermore trkB phosphorylation, and thus BDNF signaling, is reduced in both NCAM knockout mice and Endo-N-treated slice cultures [18].
• Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors [19].
• Moreover, cortical NPY neuron numbers increased after NT4 and BDNF transfection of a cocultured tectal explant innervated selectively by cortical layer V pyramidal neurons [20].

Anatomical context of Bdnf

• Bdnf was expressed in the myocytes of the viable border zone [16].
• Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum [12].
• In adult rats, injection of NT-3 (but not BDNF) into the lesioned spinal cord increases the regenerative sprouting of the transected CST [21].
• BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro [1].
• Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra [1].

Associations of Bdnf with chemical compounds

• Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are secreted and cleaved extracellularly by the serine protease plasmin and by selective matrix metalloproteinases (MMPs) [22].
• In contrast to BDNF, the action of NT4 was independent of calcium influx through NMDA receptors and L-type calcium channels [20].
• Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons [23].
• The effects of BDNF and NT-3 on dopamine uptake activity showed no additivity [24].
• In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula [25].

Physical interactions of Bdnf

• Herein, we determined whether some kinases of this pathway connect BDNF to the cyclic AMP response element -binding protein (CREB), a transcription factor also involved in plasticity and survival [26].
• A calcium/calmodulin kinase pathway connects brain-derived neurotrophic factor to the cyclic AMP-responsive transcription factor in the rat hippocampus [26].
• BDNF binds to TrkB, a receptor tyrosine kinase, which results in the activation of a variety of signaling molecules to exert the various functions of BDNF [27].
• Brain-derived neurotrophic factor and the anti-p75 monoclonal antibody MC192 have been shown to interfere with the binding of nerve growth factor to p75 [28].

Enzymatic interactions of Bdnf

• In contrast, multiple bolus microinjections of BDNF accelerated kindling development and did not affect the level of phosphorylated Trks or TrkB receptors [29].
• In contrast to shams, the acutely exercised FPI rats failed to show activity-dependent BDNF upregulation and had significant decreases of phosphorylated synapsin I and total CREB [30].
• These factors may act as the eventual repressors for BDNF expression via competition and heterodimerization with phosphorylated CREB, a transcription factor important for BDNF expression [31].
• Shp-2 specifically regulates several tyrosine-phosphorylated proteins in brain-derived neurotrophic factor signaling in cultured cerebral cortical neurons [27].

Co-localisations of Bdnf

• The BDNF mRNA signal belatedly co-localizes with CRH and AVP mRNA signals in the PVN, as determined by in situ hybridization [32].
• BDNF was preferentially colocalized with glutamatergic markers VGLUT1 and NR1 ( approximately 30% each) [33].
• Although hippocampal neurons do not express typical LDCV proteins, transfected chromogranins A, B, and brain-derived neurotrophic factor (BDNF) colocalize with VMAT2 [34].

Regulatory relationships of Bdnf

• The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3 [35].
• Intracerebroventricular BDNF injections (5 microg/rat) in non-anesthetized adult male rats induce a gradual increase in the CRH mRNA signal whereas AVP mRNA signal progressively decreases in the parvocellular and magnocellular PVN portions [32].
• Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB [36].
• AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3-kinase-dependent activation in extracellular signal-regulated kinase to upregulate BDNF gene expression [37].
• The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity [38].

Other interactions of Bdnf

• We find that NT-3 injected locally specifically enhances this sprouting, whereas BDNF has no effect [21].
• A marked increase of BDNF and NT-4 mRNAs in the distal segment of the sciatic nerve was seen 2 wk after the lesion [39].
• Transcellular induction of neuropeptide Y expression by NT4 and BDNF [20].
• BDNF protein was rapidly upregulated within 24 hr after lesion, whereas CNTF protein upregulation was delayed reaching maximal levels by 3 d [40].
• Because sustained [Ca2+]i is believed to be causally related to neuronal injury, we suggest that BDNF and FGF2 may protect cerebellar granule cells against excitotoxicity by altering the NMDA receptor-Ca2+ signaling via a downregulation of NMDA receptor subunit expression [41].

Analytical, diagnostic and therapeutic context of Bdnf

• The increase in BDNF mRNA was mediated by a selective activation of the BDNF exon IV promoter and adrenalectomy attenuated this increase by 50% [39].
• In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants [42].
• In situ hybridizations for BDNF and trkB mRNA revealed that virtually all CSNs express trkB, whereas only half of them express BDNF [43].
• As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip [25].
• We found that single or repeated immobilization markedly reduced brain-derived neurotrophic factor (BDNF) mRNA levels in the dentate gyrus and hippocampus [44].

References