Liver hydrolysate produces antidepressant and antidementia effects in olfactory bulbectomized mice

[Speaker] Osamu Nakagawasai:1
[Co-author] Kotaro Yamada:2, Takayo Odaira:1, Wakana Sakuma:1, Wataru Nemoto:1, Hidetomo Sakurai:2, Koichi Tan-No:1
1:Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan, 2:Consumer Healthcare Products Development, ZERIA Pharmaceutical Co., Ltd., Japan

[Background] Some studies demonstrated that voluntary exercise improves depressive symptoms and cognitive dysfunctions through AMP-activated protein kinase (AMPK) activation. We reported that liver hydrolysate (LH) produced an anti-fatigue effect through activation of AMPK in the liver and soleus muscle (Nakagawasai et al., J. Pharmacol. Sci. 123, 328-35, 2013). However, the effects of LH on emotional and cognitive functions are unknown. The aim of this study was to explore the effects and underlying mechanisms of LH on depressive-like behavior and memory-related behavioral impairment in olfactory bulbectomized (OBX) mice, an experimental animal model of depression and dementia.
[Methods] Male ddY mice weighing 26 - 28 g were used. Sham and OBX groups were both divided into two groups receiving either drinking water or LH in drinking water. LH treatment began either on the 7th day before operation, the operation day, or the 7th day after operation. Depressive-like behavior was measured as the prolonged immobility time in the tail-suspension test on the 21st day after operation. Long-term memory was assessed using the step-through passive avoidance test on the 28th day after operation. The expression of hippocampal phosphorylated AMPK, phosphorylated cyclic-AMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) were measured by immunoblot.
[Results] Our results show that oral administration of LH from the 7th day after operation reversed the prolonged immobility time in OBX mice. Daily administration of LH from 7th day before operation protected against the impairment of memory-related behavior in OBX mice. Immunoblotting studies revealed that pAMPK, pCREB and BDNF were significantly increased in the hippocampus of OBX mice treated with LH.
[Conclusions] The present study has shown that LH has antidepressant and antidementia via hippocampal AMPK/CREB/BDNF signaling pathways.
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