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- W2000994300 abstract "Type 2 diabetes mellitus (T2DM) is known to be associated with increased risk of cognitive impairment including Alzheimer's disease. Recent studies proposed the interaction between angiotensin II and N-Methyl-D-aspartic acid (NMDA) glutamate receptors. We reported that stimulation of angiotensin II type 2 (AT 2) receptor exerts brain protective effects partly due to an increase in cerebral blood flow (CBF) and enhancement of neuronal differentiation. Newly developed AT 2 receptor agonist, compound 21 (C21), enables us to examine the effect of direct AT 2 receptor stimulation in vivo. Accordingly, we examined the possible synergistic effect of C21 and memantine on cognitive impairment in T2DM mice. Ten week-old male T2DM mice, KKAy, were divided into four groups; 1) control, 2) treatment with C21 (10 m g/kg/day), 3) treatment with memantine (20 mg/kg/day), 4) treatment with both memantine and C21 for 2 weeks. Mice were subjected to the Morris water maze tasks. Cerebral blood flow (CBF) was analyzed by 2D-laser speckle flowmetry. Extracellular acetylcholine concentrations in the striatum were measured by in vivo microdialysis. Blood pressure, plasma glucose concentration and body weight were not different among all groups. KKAy showed impaired spatial leaning memory in the Morris water maze tasks. Treatment with C21 or memantine alone at these doses tended to shorten escape latency compared to the control group without significant difference. C21 treatment increased CBF, but memantine did not influence CBF. Treatment with C21, memantine or C21 plus memantine tended to increase hippocampal field-excitatory postsynaptic potential (f-EPSP). However, interestingly, we observed that co-administration of C21 and memantine significantly improved swim latency in KKAy. Moreover, we observed that treatment with memantine increased acetylcholine levels, which was lower in KKAy compared to wild-type mice, and that C21 treatment enhanced memantine-induced acetylcholine secretion. Furthermore, we observed that treatment with C21 promoted neurite outgrowth of cultured hippocampal neurons. T his study will provide us with new idea of approaches to understand the interaction of angiotensin II and neurotransmitter. We could expect new therapeutic approach against cognitive decline with C21 and memantine." @default.
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- W2000994300 date "2013-07-01" @default.
- W2000994300 modified "2023-09-27" @default.
- W2000994300 title "P2-029: Possible synergistic effect of direct angiotensin II type 2 receptor stimulation by compound 21 with memantine on cognitive impairment in type 2 diabetic mouse" @default.
- W2000994300 doi "https://doi.org/10.1016/j.jalz.2013.05.671" @default.
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