Calmodulin Mediates Brain-derived Neurotrophic Factor Cell Survival Signaling Upstream of Akt Kinase in Embryonic Neocortical Neurons

Cheng, Ann‐Lii; Wang, Shuqin; Yang, Dongmei; Xiao, Rui-Ping; Mattson, Mark P.

doi:10.1074/jbc.m207232200

Cited by 86 publications

(74 citation statements)

References 68 publications

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“…It has been shown previously that BDNF can rescue neurons from injury-induced death [36][37][38][39]. BDNF may exerts this neuroprotective effects through calmodulin [48,49]. BDNF may also be involved in the suppression of injury-induced delayed apoptosis [50], possibly through the increase of the antiapoptotic molecule, Bcl-xl [51].…”

Section: Discussionmentioning

confidence: 96%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

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The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.

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Section: Discussionmentioning

confidence: 96%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

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“…The Akt pathway is activated by the C fragment of the tetanus toxin after 30 minutes of incubation with neuronal cultures, and afterwards the activation decreases [34,35]. On the contrary, the activation with BDNF extends after this time, up to 240 minutes [36]. For this reason, in order to know if the neurotrophic factor remained active, the induction of the Akt pathway was analysed after 60 minutes in cortical neuronal cells treated with the BDNF-TTC, in which time no TTC effect should be observed.…”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

Ciriza¹,

García‐Ojeda

Martín-Burriel³

et al. 2008

Open Life Sciences

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Neurotrophic factors have been widely suggested as a treatment for multiple diseases including motorneuron pathologies, like Amyotrophic Lateral Sclerosis. However, clinical trials in which growth factors have been systematically administered to Amyotrophic Lateral Sclerosis patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. A possible strategy is the use of the atoxic C fragment of the tetanus toxin as a neurotrophic factor carrier to the motorneurons.The activity of trophic factors should be tested because their genetic fusion to proteins could alter their folding and conformation, thus undermining their neuroprotective properties. For this purpose, in this paper we explored the Brain Derived Neurotrophic Factor (BDNF) activity maintenance after genetic fusion with the C fragment of the tetanus toxin. We demonstrated that BDNF fused with the C fragment of the tetanus toxin induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and maintains its antiapoptotic neuronal activity in Neuro2A cells.

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“…26,27 As shown in Figure 6a, the culture that received adenovirus expressing EGFP alone exhibited a slight increase of cells within the first 2 days after B27 withdrawal and thereafter a decreased cell viability was observed, as determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8) formazan assay. In contrast, the cultures that received adenovirus expressing FosB or DFosB exhibited more growth than the control cells within the first 2 days, and showed a decreased viability on the 4th day.…”

mentioning

confidence: 97%

Selective induction of ΔFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of ΔFosB and galectin-1 in neuroprotection and neurogenesis

et al. 2005

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Transient forebrain ischemia causes selective induction of DFosB, an AP-1 (activator protein-1) subunit, in cells within the ventricle wall or those in the dentate gyrus in the rat brain prior to neurogenesis, followed by induction of nestin, a marker for neuronal precursor cells, or galectin-1, a b-galactoside sugarbinding lectin. The adenovirus-mediated expression of FosB or DFosB induced expression of nestin, glial fibrillary acidic protein and galectin-1 in rat embryonic cortical cells. DFosBexpressing cells exhibited a significantly higher survival and proliferation after the withdrawal of B27 supplement than the control or FosB-expressing cells. The decline in the DFosB expression in the survivors enhanced the MAP2 expression. The expression of DFosB in cells within the ventricle wall of the rat brain also resulted in an elevated expression of nestin. We therefore conclude that DFosB can promote the proliferation of quiescent neuronal precursor cells, thus enhancing neurogenesis after transient forebrain ischemia.

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Calmodulin Mediates Brain-derived Neurotrophic Factor Cell Survival Signaling Upstream of Akt Kinase in Embryonic Neocortical Neurons

Cited by 86 publications

References 68 publications

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

Selective induction of ΔFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of ΔFosB and galectin-1 in neuroprotection and neurogenesis

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