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Bacopa monnieri Ameliorates Memory Deficits in Olfactory Bulbectomized Mice: Possible Involvement of Glutamatergic and Cholinergic Systems

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Abstract

This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-d-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

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Acknowledgments

This work was in part supported by a Grant-in-Aid for the 2010 and 2012 Cooperative Research Project II from the Institute of Natural Medicine, University of Toyama (to H. T. N. P. and K. M.). L. T. X. is the recipient of a scholarship from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Xoan Thi Le, Hang Thi Nguyet Pham, Phuong Thi Do, Hironori Fujiwara & Kinzo Matsumoto

  2. Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama, Japan

    Ken Tanaka

  3. Research Promotion Office, Institute of Natural Medicine, University of Toyama, Toyama, Japan

    Feng Li

  4. National Institute of Medicinal Materials, Hanoi, Vietnam

    Xoan Thi Le, Hang Thi Nguyet Pham, Phuong Thi Do, Tai Van Nguyen & Khoi Minh Nguyen

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  1. Xoan Thi Le
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Le, X.T., Pham, H.T.N., Do, P.T. et al. Bacopa monnieri Ameliorates Memory Deficits in Olfactory Bulbectomized Mice: Possible Involvement of Glutamatergic and Cholinergic Systems. Neurochem Res 38, 2201–2215 (2013). https://doi.org/10.1007/s11064-013-1129-6

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