Caspase inhibition decreases cell death in regions of adult neurogenesis.
The generation of new neurons in adult neurogenic regions is paralleled by a high rate of cell death. To further characterize the interplay between generation and removal of new cells, we studied the role of caspase 2 (Nedd 2) and 3 (CPP 32) on the basis of the high expression of these cysteine proteases in neurogenic regions. By injecting the broad spectrum caspase inhibitor BOC-Asp(OMe)-fluoromethyl ketone into the lateral ventricle of adult rats, a 60% ;reduction of terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) profiles was observed in all neurogenic regions without changing the number of newly generated cells. These data suggest that inhibiting the caspase activity in vivo decreases the rate of cell death, but has no influence on the generation of new neurons.
Biebl
Manfred
M
Department of Neurology, University of Regensburg, Regensburg, Germany.
Winner
Beate
B
Winkler
Jürgen
J
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C103192:butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone; D020169:Caspases; D001973:Bromodeoxyuridine