PACAP and NGF cooperatively enhance choline acetyltransferase activity in postnatal basal forebrain neurons by complementary induction of its different mRNA species.
Both nerve growth factor (NGF) and pituitary adenylate cyclase activating polypeptide (PACAP) have neurotrophic effects on basal forebrain cholinergic neurons. They promote differentiation, maturation, and survival of these cholinergic neurons in vivo and in vitro. Here we report on the cooperative effects of NGF and PACAP on postnatal, but not embryonic, cholinergic neurons cultured from rat basal forebrain. Combined treatment with NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and PACAP induced an additive increase in choline acetyltransferase (ChAT) activity. There were no cooperative effects on the number of cholinergic neurons, suggesting that ChAT mRNA expression had been induced in each cholinergic neuron. Further analysis revealed that NGF and PACAP led to complementary induction of different ChAT mRNA species, thus enhancing total ChAT mRNA expression. These results explain the cooperative neurotrophic action of NGF and PACAP on postnatal cholinergic neurons.
Yuhara
Aki
A
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Ishii
Kyoko
K
Nishio
Chika
C
Abiru
Yasuhiro
Y
Yamada
Masashi
M
Nawa
Hiroyuki
H
Hatanaka
Hiroshi
H
Takei
Nobuyuki
N
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; C073922:neurotrophin 4