Novel cognitive enhancer SAK3 improves cognitive impairments by methimazole-induced hypothyroidism
-
1
Tohoku University Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Japan
Methimazole (MMI) is used as the first-line therapy in the hyperthyroidism and Graves' disease management. Nonetheless, the long term MMI therapy can ignite hypothyroidism which in turn can be an indirect cause of neuropsychiatric toxicity. Hypothyroidism has been implicated with depression, dementia in the patients. Recently, we have developed novel cognitive enhancer spiroimidazopyridine derivative SAK3 (PCT/JP2013/51388). Here, we investigate the potential therapeutic properties of SAK3 in the hypothyroidism mice induced by MMI. Acute exposure of MMI impaired cognition and spatial memory which have been improved by administration of SAK3 (0.1, 0.5 and 1 mg/kg). The choline acetyltransferase (ChAT) is known to rate-limiting enzyme that produces acetylcholine. Notably, MMI treated mice showed a significant decrease in ChAT positive cells in the medial septum area. The SAK3 (0.1, 0.5 and 1 mg/kg) administration restored the reduction of ChAT positive cell numbers seen in MMI-treated mice. Taking into account, SAK3 treatment is an attractive therapeutic strategy to attenuate cognitive dysfunction of patients with hypothyroidism via improvement of impaired cholinergic neurons.
Keywords:
Hypothyroidism,
therapy,
in vivo,
cognitive enhancer,
cholinergic neurones
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Poster Presentation Session
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Husain
N,
Yabuki
Y and
Fukunaga
K
(2016). Novel cognitive enhancer SAK3 improves cognitive impairments by methimazole-induced hypothyroidism.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00177
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Prof. Kohji Fukunaga, Tohoku University Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Sendai, Miyagi, 980-8578, Japan, fukunaga@mail.phar.tohoku.ac.jp