Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish

Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200 μM physostigmine, which was inhibited by pretreatment with 200 μM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200 μM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30 min treatment with 200 μM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200 μM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20 μM physostigmine. These results suggest that 200 μM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish.