- Mast cells and histamine
- Sleep and Wakefulness Research
- Circadian rhythm and melatonin
- Olfactory and Sensory Function Studies
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Alzheimer's disease research and treatments
- Polyamine Metabolism and Applications
- Allergic Rhinitis and Sensitization
- Amino Acid Enzymes and Metabolism
- Neuroendocrine regulation and behavior
- Cholinesterase and Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Pharmacy and Medical Practices
- Neuropeptides and Animal Physiology
- Dementia and Cognitive Impairment Research
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Immune Cell Function and Interaction
- Sleep and related disorders
- Hemodynamic Monitoring and Therapy
- Cancer, Stress, Anesthesia, and Immune Response
- Neurological disorders and treatments
- Advanced Glycation End Products research
Hokkaido University
2024-2025
Tohoku Medical and Pharmaceutical University
2016-2024
Tohoku University
2013-2024
Beth Israel Deaconess Medical Center
2018-2024
Tohoku Medical and Pharmaceutical University Hospital
2018-2023
American Pharmacists Association
2022
Pharmac
2020
Harvard University
2018-2019
Komatsu (Japan)
2017
Histamine clearance is an essential process for avoiding excessive histaminergic neuronal activity. Previous studies using rodents revealed the predominant role of astrocytes in brain histamine clearance. However, molecular mechanism has remained unclear. We detected N ‐methyltransferase (HNMT), a histamine‐metabolizing enzyme, primary human and specimens. Immunocytochemical analysis subcellular fractionation assays that active HNMT localized to cytosol, suggesting transport into cytosol...
Histamine is a neurotransmitter that regulates diverse physiological functions including the sleep-wake cycle. Recent studies have reported histaminergic dysfunction in brain associated with neuropsychiatric disorders. N-methyltransferase (HNMT) an enzyme expressed central nervous system specifically metabolises histamine; yet, exact roles of HNMT are unknown. Accordingly, we phenotyped Hnmt knockout mice (KO) to determine relevance various functions. First, showed deficiency enhanced...
Sleep and wakefulness are greatly influenced by various physiological psychological factors, but the neuronal elements responsible for organizing sleep-wake behavior in response to these factors largely unknown. In this study, we report that a subset of neurons lateral hypothalamic area (LH) expressing neuropeptide neurotensin (Nts) is critical orchestrating responses acute challenges or stressors. We show selective activation NtsLH with chemogenetic optogenetic methods elicits rapid...
Abstract Histamine plays a role as neurotransmitter to exert wake-promoting effects in the brain. Decreased histamine concentration cerebrospinal fluid of narcolepsy patients suggested that dysfunction system was involved pathophysiology, suggesting drugs increasing brain level ameliorated symptoms. Thus, we hypothesized inhibition metabolizing enzyme, N-methyltransferase (HNMT), could increase and alleviate cataplexy by activating system. First, examined pharmacological actions metoprine,...
Histamine is a physiological amine which initiates multitude of responses by binding to four known G-protein coupled histamine receptor subtypes as follows: H1 (H1 R), H2 R, H3 and H4 R. Brain elicits neuronal excitation regulates variety processes such learning memory, sleep-awake cycle appetite regulation. Microglia, the resident macrophages in brain, express receptors; however, effects on critical microglial functions chemotaxis, phagocytosis, cytokine secretion have not been examined...
Abstract Histamine is an important neurotransmitter that contributes to various processes, including the sleep-wake cycle, learning, memory, and stress responses. Its actions are mediated through histamine H 1 –H 4 receptors. Gene knockout pharmacological studies have revealed importance of receptors in learning regulation aggression, wakefulness. abundantly expressed on neurons astrocytes. However, date, selectively investigating roles neuronal astrocytic behaviour lacking. We generated...
Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, mechanism of transport by is not entirely clear. We aimed elucidate transporters responsible for 1321N1, a human astrocytoma-derived cell line. First, we confirmed 1321N1 cells transported dopamine, serotonin, norepinephrine, histamine time- dose-dependent manner. Kinetics...
The dysregulation of monoamine clearance in the central nervous system occurs various neuropsychiatric disorders, and role polyspecific transporters is increasingly highlighted recent studies. However, no study to date has properly characterized mouse brain. In present study, we examined kinetic properties three [organic cation transporter 2 (Oct2), Oct3, plasma membrane (Pmat)] compared absolute mRNA expression levels these brain areas. First, evaluated affinities each for noradrenaline,...
ORIGINAL RESEARCH article Front. Syst. Neurosci., 11 June 2012 https://doi.org/10.3389/fnsys.2012.00045
Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation histaminergic neurons in tuberomamillary nucleus (HA TMN neurons) has produced inconsistent effects on sleep–wake cycle, possibly due use Hdc-Cre mice driving Cre recombinase and DREADDs activity outside targeted region. Moreover, previous studies have not examined locomotor...
Abstract Quantification of in vivo reactive astrogliosis, which represents neural inflammation and remodeling the brain, is an emerging methodology for evaluation patients with neurodegenerative diseases. [18F]THK-5351 a positron emission tomography (PET) tracer monoamine oxidase B (MAO-B), molecular marker astrogliosis. We performed PET patient who at autopsy was found to have argyrophilic grain disease (AGD) comorbid pathology visualize astrogliosis first time. aimed validate...
Pancreatic α‐cells secrete glucagon to maintain energy homeostasis. Although histamine has an important role in homeostasis, the expression and function of receptors pancreatic remains unknown. We found that H 3 receptor (H R) was expressed mouse αTC1.6 cells, a α‐cell line. R inhibited secretion from cells by inhibiting increase intracellular Ca 2+ concentration. also immepip, selective agonist, decreased serum concentration rats. These results suggest modulates α‐cells.
Abstract Purpose Noninvasive imaging of protein aggregates in the brain is critical for early diagnosis, disease monitoring, and evaluation effectiveness novel therapies Alzheimer’s (AD). Near-infrared fluorescence (NIRF) with specific probes a promising technique vivo detection deposits without radiation exposure. Comprehensive screening fluorescent compounds identified compound, THK-565, amyloid-β (Aβ) mouse brain. This study assessed whether THK-565 could detect AD model. Procedures The...