ABSTRACT
Previously, we reported that ovariectomy (OVX) combined with ß-amyloid peptide (Aß) impaired spatial memory by decreasing extracellular acetylcholine (ACh) levels in the dorsal hippocampus. Here, we investigated the effect of tokishakuyakusan (TSS), a Kampo medicine, on the impairment of spatial memory induced by OVX combined with Aß in rats. Repeated administration of TSS (300 mg/kg, p.o.) significantly decreased the number of errors in the eight-arm radial maze test. Though TSS had no effect on extracellular ACh levels at baseline, TSS significantly increased extracellular ACh levels in the dorsal hippocampus. These results suggest that TSS improves the impairment of spatial memory induced by OVX combined with Aß by (at least in part) increasing extracellular ACh levels in the dorsal hippocampus.
Subject(s)
Acetylcholine/metabolism , Amyloid beta-Peptides/toxicity , Drugs, Chinese Herbal/pharmacology , Hippocampus/metabolism , Memory Disorders/drug therapy , Memory Disorders/etiology , Ovariectomy/adverse effects , Spatial Memory/drug effects , Animals , Drugs, Chinese Herbal/administration & dosage , Female , Maze Learning/drug effects , Memory Disorders/psychology , Rats, WistarABSTRACT
Amyloid beta protein (Abeta) is the major component of senile plaques, the pathological hallmark of the neurodegeneration associated with Alzheimer's disease (AD). This study investigated the effect of Toki-shakuyaku-san (TSS), a traditional medicine, on Abeta25-35-induced neuronal death and lipid peroxidation assessed by measuring lactate dehydrogenase (LDH) and malondialdehyde (MDA), respectively. Abeta25-35 at 10 microM induced neuronal damage and increased the LDH and MDA. TSS at concentrations of 100 and 300 microg/mL significantly reduced the Abeta25-35-induced neuronal death and the lipid peroxidation. These results suggest that TSS has a protective effect against Abeta25-35-induced neuronal damage. TSS may be beneficial for the treatment of AD.
Subject(s)
Drugs, Chinese Herbal , Neurons/drug effects , Neuroprotective Agents/pharmacology , Phytotherapy , Amyloid beta-Peptides , Animals , Apoptosis/drug effects , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Dose-Response Relationship, Drug , L-Lactate Dehydrogenase/metabolism , Lipid Peroxidation/drug effects , Malondialdehyde/metabolism , Neurons/cytology , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/therapeutic use , Peptide Fragments , Rats , Rats, WistarABSTRACT
Previously we have reported that Toki-shakuyaku-san (TSS) ameliorated the impairment of spatial memory induced by single cerebral ischemia (1 x 10 minutes) and scopolamine, a muscarinic receptor antagonist. In this experiment, we studied the effect of TSS on repeated cerebral ischemia (2 x 10 minutes, 1-hour interval) induced impairment of spatial memory and neuronal injury in rats. The 8-day post-ischemic treatment with TSS (30-300 mg/kg) was administered p.o. once per day. TSS dose-dependently prevented the impairment of spatial memory, neuronal death and TUNEL positive cells induced by repeated cerebral ischemia. In order to determine the mechanism of TSS, we also studied the effect of TSS on GluR2 mRNA, one of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor subunits. Repeated cerebral ischemia significantly decreased GluR2 flop mRNA at 1 and 3 days after the occlusion. TSS (300 mg/kg) significantly suppressed the decrease in GluR2 flop at 3 days after repeated cerebral ischemia. These results suggested that the TSS has neuroprotective action which may be indirectly mediated by the AMPA receptor, and TSS may be beneficial for the treatment of cerebrovascular dementia.