Biomedical subjects

Hatsue Waki

Publications and source records attributed to Hatsue Waki.

4 recordsLinked to original sources

PubMed2004

Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats.

The effects of long-term carnitine supplementation on age-related changes in tissue carnitine levels and in lipid metabolism were investigated. The total carnitine levels in heart, skeletal muscle, cerebral cortex, and hippocampus were approximately 20% less in aged rats (22 months old) than in young rats (6 months old). On the contrary, plasma carnitine levels were not affected by aging. Supplementation of acetyl-l-carnitine (ALCAR; 100 mg/kg body weight/day for 3 months) significantly increased tissue carnitine levels in aged rats but had little effect on tissue carnitine levels in young rats. Plasma lipoprotein analyses revealed that triacylglycerol levels in VLDL and cholesterol levels in LDL and in HDL were all significantly higher in aged rats than in young rats. ALCAR treatment decreased all lipoprotein fractions and consequently the levels of triacylglycerol and cholesterol. The reduction in plasma cholesterol contents in ALCAR-treated aged rats was attributable mainly to a decrease of cholesteryl esters rather than to a decrease of free cholesterol. Another remarkable effect of ALCAR was that it decreased the cholesterol content and cholesterol-phospholipid ratio in the brain tissues of aged rats. These results indicate that chronic ALCAR supplementation reverses the age-associated changes in lipid metabolism.

Acetylcarnitine↗

PubMed2004

Synaptic function of cholinergic-specific Chol-1alpha ganglioside.

The function of a cholinergic-specific ganglioside, Chol-1alpha, was investigated. The release of acetylcholine from synaptosomes was inhibited by anti-Chol-1alpha monoclonal antibody but not by monoclonal antibodies against other brain gangliosides tested. Chol-1alpha ganglioside stimulated the high-affinity choline uptake by synaptosomes and consequently enhanced acetylcholine synthesis, resulting in an increased release of acetylcholine from synaptosomes. The memory and learning abilities of rats given anti-Chol-1alpha antibody were remarkably suppressed. These in vitro and in vivo studies suggest that Chol-1alpha ganglioside plays a pivotal role in cholinergic synaptic transmission and participates in cognitive function.

Animals↗

PubMed2002

Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine.

A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration.

Aging↗

PubMed2002

Effects of the mono- and tetrasialogangliosides GM1 and GQ1b on ATP-induced long-term potentiation in hippocampal CA1 neurons.

The effects of the mono- and tetrasialogangliosides, GM1 and GQ1b, on ATP-induced long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Application of 5 or 10 microM ATP for 10 min resulted in a transient depression followed by a slow augmentation of synaptic transmission, leading to LTP. LTP induced by treatment with 5 microM ATP was facilitated in hippocampal slices prepared from animals treated for 6 days with a ceramide analog, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol, which stimulates ganglioside biosynthesis. In addition, LTP induced by 5 microM ATP was significantly enhanced when naive slices were incubated with GQ1b but not with GM1. These results suggest that a cooperative effect between extracellular ATP and GQ1b enhances ATP-induced LTP in hippocampal CA1 neurons. In addition, the LTP induced by 10 microM ATP was blocked by coapplication of the NMDA antagonist AP5 (5 microM or 50 microM), and this effect was partially inhibited by GQ1b pretreatment of the slices, suggesting that in hippocampal CA1 neurons, the enhancing effect of GQ1b on ATP-induced LTP is mediated by modulation of NMDA receptors/Ca(2+) channels.

Adenosine Triphosphate↗