Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS).
Nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells can be increased after the treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Since the increase of NGF is not blocked by the treatment with decarboxylase inhibitor, DOPS may have direct effect to increase the NGF content. NGF and its receptor (NGFR) are suggested to play an important role in the neuronal survival and regeneration under pathologic conditions. In this study, we studied a possible protective effect of DOPS against the hippocampal CA1 cell death after transient forebrain ischaemia in gerbils in relation to the change of NGFR immunoreactivity. We found that treatment with DOPS (300 mg kg-1) in combination with a decarboxylase inhibitor (benserazide, 10 mg kg-1) protected ischaemic hippocampal CA1 cell against delayed neuronal death (neuronal density = 125 +/- 24 mm-1) as compared to the treatment with vehicle (49 +/- 11 mm-1) (p < 0.01). The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group. However, it was slightly and transiently induced from 8 h to 2 days in the DOPS plus benserazide treated group. These data suggest that the protective role of DOPS on the ischaemic hippocampal CA1 cells may act through the NGF and its receptor system.
Lee
T H
TH
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Abe
K
K
Nakamura
M
M
Kogure
K
K
Itoyama
Y
Y
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D015103:Droxidopa / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D017475:Receptors, Nerve Growth Factor; D001545:Benserazide; D015103:Droxidopa