Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation

Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation

Abstract
Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKII╬▒ (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKC╬▒ (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR.

Scientific Studies & Papers

Author of Study or Paper
Moriguchi S, Tanaka T, Tagashira H, Narahashi T, Fukunaga K.
Source
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
Date Published
2013 in Behavioural brain research.

Contact Us

Email
Info@LimitlessMindset.com
Phone
+1 720 924 1872

Community Login

Content Copyright 2011 - 2023 LimitlessMindset.com. All Rights Reserved.

  • All trademarks, logos, and service marks displayed are registered and/or unregistered Trademarks of their respective owners.
  • Reproduction in whole or in any form without express written permission is prohibited.
  • This is not medical advice.
  • The content on this website is for entertainment purposes.
  • These statements have not been evaluated by the Food and Drug Administration.
  • These products are not intended to treat, cure, prevent, or diagnose any disease.

Website by Roseland Digital