Biology subjects

Shioda, S.

Publications and source records attributed to Shioda, S..

3 recordsLinked to original sources

bioRxiv2020

Angiopathy with impaired glucose logistics observed in schizophrenia-like model mice

Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high-simple-sugar diets contribute to pathogenesis of these diseases. Here we demonstrate that a high-sucrose diet during adolescence induces psychosis-related behavioral endophenotypes, including hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function in mice deficient for glyoxalase-1 (Glo1), an enzyme involved in detoxification of sucrose metabolites. Further, the high-sucrose diet induced microcapillary impairments and reduced brain glucose uptake in brains of Glo1 deficient mice. Aspirin protected against this angiopathy, enhancing brain glucose uptake, and preventing abnormal behavioral phenotypes. Similar vascular damage to our model mice was found in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.

neuroscience↗

bioRxiv2020

GPCR-mediated clearance of tau in post-synaptic compartments attenuates tau pathology in vivo

Accumulation of pathological tau in synapses has been identified as an early pathogenic event in Alzheimers disease (AD) and correlates strongly with cognitive decline in patients with AD. Tau is a cytosolic, axonal protein. However, in the disease condition, tau accumulates in post-synaptic compartments and pre-synaptic terminals, either due to missorting within neurons, trans-synaptic transfer between neurons or due to failure of clearance systems in synapses. Using a sub-cellular fractionation assay, we show that progressive deposition of seed competent tau occurs predominantly in post-synaptic compartments in a tau transgenic mouse and in AD patient brain, making these neuronal structures particularly vulnerable to tau toxicity. Tau-mediated post-synaptic toxicity could be further exacerbated by impaired proteasome activity which we detected by measuring the levels of polyubiquitin chains that target proteins to proteasomal degradation. To combat the accumulation of tau and proteasome impairment at the subcellular level, we devised a therapeutic strategy of proteasome-mediated clearance of tau restricted to the post-synaptic compartment. Utilizing the pharmacology of GPCRs, we show that in vivo stimulation of the PAC1R receptor by its ligand can propagate intracellular PKA signaling leading to enhanced synaptic proteasome activity and reduced tau in the post-synaptic compartment. Over time, clearance of post-synaptic tau led to reduced tauopathy and cognitive decline in rTg4510 mice. Together, these results highlight a novel therapeutic strategy of targeting GPCRs that propagate cAMP/PKA signaling as a tool to activate proteolysis restricted to synapses to prevent the accumulation of tau in the early stages of AD.

neuroscience↗

bioRxiv2019

Cold Vacuum Extracts of Double Cherry Blossom (Gosen-Sakura) Leaves Show Antitumor Activity

The present research examines the possibility of finding bio-molecular compounds from the double cherry blossom (termed as Gosen-Sakura of Gosen-city, Niigata-prefecture, Japan) leaves, which have been long used in the preparation of the traditional Japanese sweet (wagashi) - sakura-mochi. Based on its indicated anti-microbial properties historically, our study provides a new low temperature vacuum extraction method for extracting near natural form of water soluble leaf (cell) extracts from the Gosen-Sakura, and demonstrates the presence of some novel compound(s) with anti-tumor cell lines proliferation inhibitory affects through the MTT assay. To our knowledge, no reports exist on the sakura tree leaf (cell) extracts inhibiting tumor cell line growth. We further examined and compared the effects of known compounds with anti-tumor activity, coumarin and benzyl alcohol with Gosen-Sakura leaf extract; results lead us to hypothesize that the Gosen-Sakura leaf extract contains substance(s) other than the above 2 known compounds, with antitumor effect. Additionally, we speculate on the underlying mechanism of action of the Gosen-Sakura leaf extract by targeting cell division at the point of DNA synthesis and causing apoptosis. In conclusion, we present scientific evidence on the presence of a certain novel biomolecule(s), with anti-tumor activity, in the Gosen-Sakura leaf which has been long used as a Japanese - the sakura-mochi.

plant biology↗