Reduction in brain-derived neurotrophic factor protein level in the hippocampal CA1 dendritic field precedes the delayed neuronal damage in the rat brain.
Utilizing a specific polyclonal antibody against a peptide unique for brain-derived neurotrophic factor (BDNF), we investigated the regional and temporal profiles of immunoreactivity of the BDNF protein in the rat hippocampus after transient forebrain ischemia. The pattern of immunoreactivity for the BDNF receptor (TrkB) was also examined and compared with that for BDNF. In the early phase after ischemia, we observed a distinct regional difference in immunoreactivity between the pyramidal cell layer and the stratum radiatum of the CA1 subfield. In the pyramidal cell layer, there was a rapid and transient increase in the positive immunostaining for both BDNF and TrkB. By contrast, in the stratum radiatum there was a marked decrease in BDNF immunoreactivity, but not one in that of TrkB. One week after ischemia, high immunoreactivity for both BDNF and TrkB was observed in the reactive astrocytes in the dendritic field of the CA1 subfield. These findings suggest that a transport of BDNF from the neuronal soma to the dendrites of the stratum radiatum might be ceased after the ischemic insult. Thus, a dysfunctional autocrine mechanism of BDNF within the CA1 neuron may be involved in the pathogenesis of selective neuronal damage after ischemia.
Hanno Research Center, Taiho Pharmaceutical Co. Ltd., Saitama, Japan. yamasaki@taiho.co.jp
Y
Y
Yamasaki
T
T
Shigeno
Y
Y
Furukawa
S
S
Furukawa
D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases