Injury-induced axonal sprouting in the hippocampus is initiated by activation of trkB receptors.
Penetrating head injuries are often accompanied by the delayed development of post-traumatic epilepsy. Schaffer collateral transection leads to axonal sprouting and hyperexcitability in area CA3 of hippocampal slice cultures. We used this model to test the hypothesis that the injury-induced axonal sprouting results from increased neurotrophin signaling via trkB receptors near the lesion. Using rats and mice, we established that sprouting CA3 pyramidal cell axons are labeled with an antibody to the growth-associated protein GAP-43. We observed two- to threefold increases in the level of brain-derived neurotrophic factor and trkB protein in area CA3 by 24-48 h after Schaffer collateral transection, preceding the onset of axonal sprouting. Finally, we demonstrated that injury-induced axonal sprouting of GAP-43-immunoreactive axons is impaired in hippocampal slice cultures from mice expressing low levels of trkB receptors. We conclude that injury-induced axonal sprouting is initiated by brain-derived neurotrophic factor-trkB signaling and suggest that this process may be critical for the genesis of post-traumatic epilepsy.
Dinocourt
Céline
C
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Gallagher
Sandra E
SE
Thompson
Scott M
SM
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology* / Q000293:injuries; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D020813:Receptor, trkB / Q000172:deficiency / Q000378:metabolism*; D013266:Stilbamidines; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019922:GAP-43 Protein; D013266:Stilbamidines; D049452:Green Fluorescent Proteins; D020813:Receptor, trkB