The neurotrophic effects of ebiratide, an analog of ACTH4-9, on cultured septal cells and aged rats.
The neurotrophic effects of ebiratide, an ACTH4-9 analog, have been examined using both fetal rat septal cultures and aged rats. The 5-day treatment with ebiratide (10-100 pmol/ml) partially prevented neuronal degeneration that occurred in the cultures in which cells were sparsely plated. Ebiratide (10 pmol/ ml) increased choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities up to 1.5 and 1.2 times the respective control values in the sub-confluent cultures. AChE cytochemistry of the cultures has shown that ebiratide increased the stained area per cell. Ebiratide subcutaneously administered by constant infusion (10 nmol/body/hr) for 4 weeks elevated ChAT activities in the septum (35% over control), neocortex (79%) and hippocampus (89%) of aged rats. Thus, the present study indicates that ebiratide shares neurotrophic properties which may prove beneficial in the therapy for CNS degenerative disorders, especially Alzheimer's disease.
Matsumoto
T
T
Drug Discovery Research Laboratories, Hiroshima University School of Medicine, Japan.
Tsuda
S
S
Nakamura
S
S
D000110:Acetylcholinesterase / Q000819:agonists; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000648:ultrastructure; D002455:Cell Division; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000819:agonists; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012688:Septum Pellucidum / Q000187:drug effects* / Q000648:ultrastructure
D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; C057139:ebiratide; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase