Disease relevance of BDNF

• Following acoustic trauma, regenerated hair cells acquired BDNF mRNA expression at early stages of differentiation [1].
• These results indicate that BDNF and NT-3 may not directly regulate the expression of K+ channels in chick cochlear ganglion neurons [2].
• Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels [3].

Psychiatry related information on BDNF

• Intracerebral administration of antisense ODNs to BDNF 6-12 h prior to training induced amnesia for the avoidance response by 3 h after training [4].
• Here the role of brain-derived neurotrophic factor (BDNF) in the critical period of thermal control establishment in chicks was investigated [5].
• Role of brain-derived neurotrophic factor and presynaptic proteins in passive avoidance learning in day-old domestic chicks [6].

High impact information on BDNF

• Here we report that in vivo treatment of chick embryos with brain-derived neurotrophic factor rescues motoneurons from naturally occurring cell death [7].
• These data implicate a role for the p75 receptor in NGF's neurotoxicity and indicate that this receptor is involved in the mechanism by which ION neurons respond to BDNF and NT-3 in the target [8].
• Moreover, CaM inhibition prevented the cell survival triggered by NGF or BDNF [9].
• Previous studies suggested that there are other pro-apoptotic molecules, nerve growth factor (NGF) and brain-derived neurotrophic factor, that induce cell death in the nervous system [10].
• Retinal ganglion cells (RGC) are supported by brain-derived neurotrophic factor (BDNF), but it is not known if BDNF acts as a target-derived factor or as an afferent or autocrine trophic factor [11].

Biological context of BDNF

• Control of early cell death by BDNF in the chick retina [12].
• These results suggest that normal SRA plays a role in regulating the axonal transport of endogenous BDNF protein [13].
• During embryogenesis, BDNF mRNA was first seen in early differentiating hair cells [1].
• We found that high concentrations of BDNF and NT-3 administered together, and low concentrations of both neurotrophins combined and administered with RA suppress otocyst cell numbers after 24 h in vitro [14].
• Thus, NT-3 promotes the conversion of neuroepithelial cells into neurons, whereas BDNF and NGF control the programmed cell death (apoptosis) that affects early postmitotic neuroblasts [15].

Anatomical context of BDNF

• The addition of BDNF to embryos resulted in about 70% increase in the number of retinal ganglion cells in both E6 and E9 retinas relative to controls [12].
• Here, we show that the application of brain-derived neurotrophic factor (BDNF) to chick embryos in ovo prevented retinal cell death in the early period, whereas exogenously applied NGF and neurotrophin-3 had no such effect [12].
• BDNF is first expressed in both the pigment epithelium and neural retina of embryonic day 4 embryos, and at the same stage of development, its TrkB receptor is expressed in the neural retina [12].
• The axonal transport of retinal-derived BDNF in segments of the optic nerve as well as tectal-derived BDNF protein transported in segments of the optic tract were both significantly reduced after very brief periods of activity blockade [13].
• High levels of BDNF mRNA persisted in surviving hair cells and trkB mRNA in cochlear neurons after noise exposure [1].

Associations of BDNF with chemical compounds

• CVG cells were explanted from chick embryos after 90 h of incubation into a defined-medium containing BDNF, NT-3, or NT-4/5 and an insulin, transferrin, selenium, and progesterone supplement [16].
• Retinoic acid increases BDNF-dependent regeneration of chick retinal ganglion cells in vitro [17].
• The concurrent delivery of BDNF or GDNF with ethanol to the embryonic chick from E10 to E15 was designed to examine the capacity of these NTFs to provide in vivo neuroprotection for this ethanol-sensitive motoneuron population [3].
• Nonsynaptic factors, including corticosterone and BDNF, can modulate retention of the avoidance response, enhancing the salience of otherwise weakly retained memory [18].
• The tissue was subsequently fixed, sectioned frozen, mounted and subjected to in situ hybridization analysis using probes for brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor, trkB [19].

Physical interactions of BDNF

• When binding of brain-derived neurotrophic factor was determined in the presence of other neurotrophins, neurotrophin-3 was found efficiently to prevent the binding of brain-derived neurotrophic factor to both the ctrkB cell line and embryonic sensory neurons [20].

Regulatory relationships of BDNF

• Truncated TrkB receptors may regulate the BDNF concentration available to neurites, and they might have an important role during reinnervation [1].
• A similar high level of neurotrophin-3 neither promotes the survival of BDNF-dependent ventrolateral trigeminal ganglion neurons nor affects the dose response of these neurons to BDNF [21].

Other interactions of BDNF

• For both receptors the down-regulation was greater in NT-3-treated chicks than those treated with BDNF [22].
• BDNF and IGF-I promoted neurite outgrowth from ION explants, whereas GDNF and NT-4 had no effect [23].
• Conversely, growth cones chronically cultured in NGF rapidly increase their sensitivity to collapsin-1 with acute exposure to BDNF [24].
• IGF-I may be an afferent trophic factor for the ION, and NT-4 may act as an antagonist to BDNF, either by competing with BDNF for p75 and/or trkB binding or by signaling cell death via p75 [23].
• Treatment with BDNF-antisense reduced both BDNF mRNA and BDNF protein in the chick brain, but did not alter mRNA levels of glyceraldehyde-3-phosphate dehydrogenase [4].

Analytical, diagnostic and therapeutic context of BDNF

• After injection of all-trans RA onto the chorio-allantoic membrane of stage E16 chick embryos, axonal regeneration was monitored in organ cultures supplemented with BDNF [17].
• Amacrine cells rather than RGC were the main source of BDNF mRNA in the ganglion cell layer, as determined by in situ hybridization that was combined with retrograde labeling of RGC and destruction of RGC by optic stalk transection, followed by quantitative RT-PCR [11].
• To explore which region(s) within these neurotrophic factors might determine their differential actions on various subpopulations of peripheral neurons, a systematic series (homolog-scanning mutagenesis) of chimeric NGF/BDNF molecules was prepared using PCR overlap-extension techniques [25].

References