Occlusal Disharmony Transiently Impairs Learning and Memory in the Mouse by Increasing Dynorphin A Levels in the Amygdala

Occlusal Disharmony Transiently Impairs Learning and Memory in the Mouse by Increasing Dynorphin A Levels in the Amygdala

KENTARO YAMADA,^1,2 YUMIE ONO,^1,2, KIN-YA KUBO,³ TOSHIHARU YAMAMOTO^2,4 and MINORU ONOZUKA^1,2

¹Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka, Kanagawa, Japan
²Research Center of Brain and Oral Science, Kanagawa Dental College, Yokosuka, Kanagawa, Japan
³Seijoh University Graduate School of Health Care Studies, Tokai, Aichi, Japan
⁴Department of Human Biology, Kanagawa Dental College, Yokosuka, Kanagawa, Japan

Occlusal disharmony sometimes causes not only stiffness of neck but also psychiatric depression, suggesting that the condition of oral cavity may affect the central nervous system. Dynorphin A is an endogenous opioid peptide that specifically binds the κ-opioid receptor and has a protective role against stress. Dynorphinergic nervous system is intensely distributed in the amygdala and hippocampus that are coping areas with stress. As a model of malocclusion, we placed dental resin on the molars to increase the occlusal vertical dimension (bite-raise). After various survival times, we analyzed the amygdala and hippocampus by immunohistochemistry and immunosorbent assay (ELISA). Furthermore, the effects on learning and memory were assessed by Morris water maze test. In the amygdala, the levels of dynorphin A were increased on the 1st day after increasing the vertical dimension as indicated by immunohistochemical and ELISA assessments. The levels of dynorphin A returned to control levels on the 5th day. In the hippocampus, there were no noticeable changes in dynorphin A levels. The water maze test indicated that increasing the vertical dimension caused longer escape latency times on the 3rd day compared to those of sham-operated group. However, the bite-raised mice treated with a dynorphin antagonist, nor-binaltorphimine, showed similar escape latency times to the times of sham-operated group, even on the 3rd day. These results suggest that occlusal disharmony causes stress resulting in a transient increase of dynorphin A levels at least in the amygdala and that the increased dynorphin A levels transiently impair learning and memory.

keywords —— amygdala; dynorphin; hippocampus; malocclusion; stress

===============================

Tohoku J. Exp. Med., 2013, 230, 49-57

Correspondence: Toshiharu Yamamoto, Department of Human Biology, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan.

e-mail: t.yamamoto@kdu.ac.jp