A5003443371- Alzheimer's disease research and treatments
- Ion Transport and Channel Regulation
- Urinary Bladder and Prostate Research
- Ion channel regulation and function
- Urological Disorders and Treatments
- Neuroscience and Neuropharmacology Research
- Hormonal Regulation and Hypertension
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebrospinal fluid and hydrocephalus
- Nitric Oxide and Endothelin Effects
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Ureteral procedures and complications
- Spinal Dysraphism and Malformations
- Heart Failure Treatment and Management
- Virus-based gene therapy research
- Renin-Angiotensin System Studies
- Pelvic floor disorders treatments
- Electrolyte and hormonal disorders
- Neuroendocrine regulation and behavior
- Parkinson's Disease Mechanisms and Treatments
- Pediatric Urology and Nephrology Studies
- Cardiac electrophysiology and arrhythmias
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
The University of Tokyo
2015-2024
Sanraku Hospital
1994-2023
St. Marianna University School of Medicine
2022
Ono Pharmaceutical (Japan)
2021
National Institute of Health Sciences
2017
Osnabrück University
2017
Takeda (Japan)
2017
Osaka University
1999-2017
Hope Center for Neurological Disorders
2013-2014
Okayama University
2009-2013
Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it also found in the extracellular space of brain at appreciable concentrations. Although its presence there may be relevant to intercellular spread tau pathology, cellular mechanisms regulating release into are not well understood. To test this context neuronal networks vivo, we used vivo microdialysis. Increasing activity rapidly increased steady-state levels vivo. Importantly, presynaptic glutamate sufficient...
Although tau is a cytoplasmic protein, it also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated can be transferred between cells and aggregates might mediate spread of pathology. Despite these data, details whether normally released into the interstitial fluid (ISF), its concentration ISF relation to CSF, influenced by aggregation are unknown. To address issues, we developed microdialysis technique analyze monomeric levels within hippocampus awake,...
Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation tau substantially reduces hyperexcitability AD mouse lines, induced seizure models, vivo models epilepsy. These data demonstrate that an important regulator excitability. However, developmental compensation knock-out line may account for protective effect against seizures. To test...
Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal (CSF). However, it remains elusive whether clearance impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), major driver glymphatic system, facilitates elimination from to CSF subsequently deep cervical lymph nodes....
α-Synuclein is a presynaptic protein abundant in the cytoplasmic compartment of neurons, whereas its presence extracellular space has also been observed under physiological conditions. Extracellular α-synuclein pathological significance, exhibiting cellular toxicity and impairment synaptic transmission. Notably, misfolded drives cell-to-cell propagation pathology via space. However, primary mechanism that regulates levels remains to be determined. Using several mechanistically distinct...
Based on epidemiological and experimental studies, type 2 diabetes mellitus (T2DM), especially insulin resistance that comprises the core mechanism of T2DM, has been recognized as a significant risk factor for Alzheimer's disease (AD). Studies in humans diabetic AD model mice have indicated correlation between increased amyloid deposition brain. Paradoxically, with targeted disruption genes involved signaling pathway showed protective effects against AD-related pathology. These conflicting...
Amyloid β (Aβ) immunotherapy is emerging as a promising disease-modifying therapy for Alzheimer's disease, although the precise mechanisms whereby anti-Aβ antibodies act against amyloid deposition and cognitive deficits remain elusive. To test “peripheral sink” theory, which postulates that effects of in systemic circulation are to promote Aβ efflux from brain blood, we studied clearance 125 I-Aβ 1-40 microinjected into mouse brains after intraperitoneal administration an monoclonal antibody...
The metabolism of amyloid β peptide (Aβ) in the brain is crucial to pathogenesis Alzheimer disease. A body evidence suggests that Aβ actively transported from parenchyma blood across blood-brain barrier (BBB), although precise mechanism remains unclear. To unravel cellular and molecular transport BBB, we established a new vitro model initial internalization step using TR-BBB cells, conditionally immortalized endothelial cell line rat brain. We show cells rapidly internalize through...
Intracellular accumulation of tau as neurofibrillary tangles (NFTs) is the hallmark Alzheimer's disease (AD) well in other tauopathies. Tau present not only cytoplasm but also extracellular space such cerebrospinal fluid (CSF) and brain interstitial (ISF). Although clearance one critical parameter leading to intracellular/extracellular accumulation, vivo turnover has been characterized. The current study attempted precisely determine rates utilizing tet-off regulatable mice. In particular,...
We recently demonstrated that stimulation of gp130 by a combination soluble interleukin 6 receptor (sIL-6R) and IL-6 but not alone significantly stimulates the ex vivo expansion primitive hematopoietic progenitors generation erythroid cells from human CD34+ in presence stem cell factor (SCF). Here, we show is found low positively on most cells, whereas IL-6R expressed only 30-50% these cells. Although colonies generated FACS-sorted CD34+IL-6R+ were granulocyte/macrophage (GM) colonies,...
Recombinant lentiviral vectors stably transduce both dividing and nondividing cells. Virus pseudotyping with vesicular stomatitis virus envelope G (VSV-G) protein broadens the host range of vector enables concentration by ultra-centrifugation. However, as a result concentration, contaminating debris derived from vector-producing cell culture media is toxic to target cells reduces transduction efficiency. Here we report new rapid technique for purifying lentivirus using strong anion exchange...
An EtOH extract of fruits Piper longum was found to exhibit a potent inhibitory effect against alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led the isolation prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These crude P. may have suppressive effects pigmentation by skin.
Natriuretic peptide type C (NPPC) and its high affinity receptor, natriuretic receptor 2 (NPR2), have been assumed to be involved in female reproduction recently shown play an essential role maintaining meiotic arrest of oocytes. However, the overall NPPC/NPR2 signaling ovarian function is still less clear. Here we report defects observed oocytes follicles mice homozygous for Nppc(lbab) or Npr2(cn), mutant alleles Nppc Npr2 respectively clarify exact consequences lack reproductive systems....
CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of hallmarks AD accumulation aggregated forms Amyloid-β (Aβ) in brain. In humans, susceptibility locus (rs9349407) associated with increased plaque burden. Aβ production highly regulated endocytosis and influenced lysosomal function. Lysosomal...
Aquaporin-4 (AQP4) has been suggested to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), which may due modulation neuroinflammation or impairment interstitial fluid bulk flow system central nervous system. Here, we show an age-dependent several behavioral outcomes 5xFAD AQP4 null mice. Twenty-four-hour video recordings and computational analyses their movement revealed that nighttime motion AQP4-deficient mice was progressively reduced...