ORCID Profile
0000-0002-8543-4590
Current Organisations
Isfahan University of Technology
,
Nagoya University Graduate School of Medicine
,
生理学研究所/National Institute for Physiological Sciences
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Publications
Dual microglia effects on blood brain barrier permeability induced by systemic inflammation
Publisher: Springer Science and Business Media LLC
Date: 20-12-2019
DOI: 10.1038/S41467-019-13812-Z
Abstract: Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.
Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity
Publisher: Wiley
Date: 29-08-2019
DOI: 10.1002/GLIA.23713
Cortical astrocytes prime the induction of spine plasticity and mirror image pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-04-2018
DOI: 10.1097/J.PAIN.0000000000001248
Abstract: Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Because synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo 2-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 after a peripheral nerve injury. We found that cross-callosal inputs enhanced the activity of both S1 astrocytes and inhibitory neurons, whereas activity of excitatory neurons decreased. When local inhibitory circuits were blocked, astrocyte-dependent spine plasticity and allodynia were revealed. Thus, we propose that cortical astrocytes prime the induction of spine plasticity and mirror image pain after peripheral nerve injury. Moreover, this result suggests that cortical synaptic rewiring could be sufficient to cause allodynia on the uninjured periphery.
Microglia Enhance Synapse Activity to Promote Local Network Synchronization
Publisher: Society for Neuroscience
Date: 09-2018
Clustering of Neuronal K+-Cl− Cotransporters in Lipid Rafts by Tyrosine Phosphorylation
Publisher: Elsevier BV
Date: 10-2009
Early Changes in KCC2 Phosphorylation in Response to Neuronal Stress Result in Functional Downregulation
Publisher: Society for Neuroscience
Date: 14-02-2007
DOI: 10.1523/JNEUROSCI.3104-06.2007
Abstract: The K + Cl − cotransporter KCC2 plays an important role in chloride homeostasis and in neuronal responses mediated by ionotropic GABA and glycine receptors. The expression levels of KCC2 in neurons determine whether neurotransmitter responses are inhibitory or excitatory. KCC2 expression is decreased in developing neurons, as well as in response to various models of neuronal injury and epilepsy. We investigated whether there is also direct modulation of KCC2 activity by changes in phosphorylation during such neuronal stressors. We examined tyrosine phosphorylation of KCC2 in rat hippoc al neurons under different conditions of in vitro neuronal stress and the functional consequences of changes in tyrosine phosphorylation. Oxidative stress (H 2 O 2 ) and the induction of seizure activity (BDNF) and hyperexcitability (0 Mg 2+ ) resulted in a rapid dephosphorylation of KCC2 that preceded the decreases in KCC2 protein or mRNA expression. Dephosphorylation of KCC2 is correlated with a reduction of transport activity and a decrease in [Cl − ] i , as well as a reduction in KCC2 surface expression. Manipulation of KCC2 tyrosine phosphorylation resulted in altered neuronal viability in response to in vitro oxidative stress. During continued neuronal stress, a second phase of functional KCC2 downregulation occurs that corresponds to decreases in KCC2 protein expression levels. We propose that neuronal stress induces a rapid loss of tyrosine phosphorylation of KCC2 that results in translocation of the protein and functional loss of transport activity. Additional understanding of the mechanisms involved may provide means for manipulating the extent of irreversible injury resulting from different neuronal stressors.
Functions of microglia in the central nervous system – beyond the immune response
Publisher: Cambridge University Press (CUP)
Date: 02-2011
DOI: 10.1017/S1740925X12000063
Abstract: Microglia cells are the immune cells of the central nervous system and consequently play important roles in brain infections and inflammation. Recent in vivo imaging studies have revealed that in the resting healthy brain, microglia are highly dynamic, moving constantly to actively survey the brain parenchyma. These active microglia can rapidly respond to pathological insults, becoming activated to induce a range of effects that may contribute to both pathogenesis, or to confer neuronal protection. However, interactions between microglia and neurons are being recognized as important in shaping neural circuit activity under more normal, physiological conditions. During development and neurogenesis, microglia interactions with neurons help to shape the final patterns of neural circuits important for behavior and with implications for diseases. In the mature brain, microglia can respond to changes in sensory activity and can influence neuronal activity acutely and over the long term. Microglia seem to be particularly involved in monitoring the integrity of synaptic function. In this review, we discuss some of these new insights into the involvement of microglia in neural circuits.
Assessment of reference evapotranspiration across an arid urban environment having poor data monitoring system
Publisher: Wiley
Date: 23-07-2020
DOI: 10.1002/HYP.13851
Abstract: Estimation of reference evapotranspiration (ET 0 ) in urban areas is challenging but essential in arid urban climates. To evaluate ET 0 in an urban environment and non‐urban areas, air temperature and relative humidity were measured at five different sites across the arid city of Isfahan, Iran, over 4 years. Wind speed and sunshine hours were obtained from an urban surrounding weather station over the same period and used to estimate ET 0 . Calculated ET 0 was compared with satellite‐based ET 0 retrieved from the MOD16A2 PET product. Although MODIS PET was strongly correlated with the Valiantzas equation, it overestimated ET 0 and showed average accuracy ( r = 0.93–0.94, RMSE = 1.18–1.28 mm/day, MBE = 0.73–0.84 mm/day). The highest ET 0 differences between an urban green space and a non‐urban area were 1.1 and 0.87 mm/day, which were estimated by ground measurements and MODIS PET, respectively. The sensitivity of ET 0 to wind speed and sunshine hours indicated a significant effect on cumulative ET 0 at urban sites compared to the non‐urban site, which has a considerable impact on the amount of irrigation required in those areas. Although MODIS PET requires improvement to accurately reflect field level microclimate conditions affecting ET 0 , it is beneficial to hydrological applications and water resource managers especially in areas where data is limited. In addition, our results indicated that using limited data methods or meteorological data from regional weather stations, leads to incorrect estimation of ET 0 in urban areas. Therefore, decision‐makers and urban planners should consider the importance of precisely estimating ET 0 to optimize management of urban green space irrigation, especially in arid and semi‐arid climates such as the city of Isfahan.
Evaluating the spatiotemporal variations of daytime surface and canopy urban heat islands: an arid climate case study
Publisher: Informa UK Limited
Date: 11-07-2022
Metallothionein promotes regenerative axonal sprouting of dorsal root ganglion neurons after physical axotomy
Publisher: Springer Science and Business Media LLC
Date: 11-08-2011
Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target
Publisher: American Association for the Advancement of Science (AAAS)
Date: 25-09-2020
Abstract: Upregulation of N-type Ca 2+ channel dependent subunits increases functional connections and synchronization for pain formation.
Microglia: actively surveying and shaping neuronal circuit structure and function
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.TINS.2012.11.007
Abstract: The traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. Recent evidence extends their role to healthy brain homeostasis, including the regulation of cell death, synapse elimination, neurogenesis, and neuronal surveillance. These actions contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Here we review microglial contributions to the development, plasticity, and maintenance of neural circuits with a focus on interactions with synapses. We introduce this topic by reviewing recent studies on the migration and proliferation of microglia within the brain, and conclude with the proposal that microglia dysfunction may adversely affect brain function, and thereby contribute to the development of psychiatric and neurological disorders.
Microglia and synapse interactions: fine tuning neural circuits and candidate molecules
Publisher: Frontiers Media SA
Date: 2013
Microglial Contact Prevents Excess Depolarization and Rescues Neurons from Excitotoxicity
Publisher: Society for Neuroscience
Date: 05-2016
DOI: 10.1523/ENEURO.0004-16.2016
Abstract: Microglia survey and directly contact neurons in both healthy and damaged brain, but the mechanisms and functional consequences of these contacts are not yet fully elucidated. Combining two-photon imaging and patch cl ing, we have developed an acute experimental model for studying the role of microglia in CNS excitotoxicity induced by neuronal hyperactivity. Our model allows us to simultaneously examine the effects of repetitive supramaximal stimulation on axonal morphology, neuronal membrane potential, and microglial migration, using cortical brain slices from Iba-1 eGFP mice. We demonstrate that microglia exert an acute and highly localized neuroprotective action under conditions of neuronal hyperactivity. Evoking repetitive action potentials in in idual layer 2/3 pyramidal neurons elicited swelling of axons, but not dendrites, which was accompanied by a large, sustained depolarization of soma membrane potential. Microglial processes migrated to these swollen axons in a mechanism involving both ATP and glutamate release via volume-activated anion channels. This migration was followed by intensive microglial wrapping of affected axons and, in some cases, the removal of axonal debris that induced a rapid soma membrane repolarization back to resting potentials. When the microglial migration was pharmacologically blocked, the activity-induced depolarization continued until cell death ensued, demonstrating that the microglia–axon contact served to prevent pathological depolarization of the soma and maintain neuronal viability. This is a novel aspect of microglia surveillance: detecting, wrapping, and rescuing neuronal soma from damage due to excessive activity.
Microglia contact induces synapse formation in developing somatosensory cortex
Publisher: Springer Science and Business Media LLC
Date: 25-08-2016
DOI: 10.1038/NCOMMS12540
Abstract: Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8–10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca 2+ transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.
In Vivo Two-Photon Imaging of Microglial Synapse Contacts
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9658-2_20
Abstract: Microglia are traditionally known as immune sentinels of the brain and as key player in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, or amyotrophic lateral sclerosis. Recently, they were also identified as synaptic organizer, promoting formation and maturation of synapses as well as modifying synaptic activity. Interestingly, microglia-mediated synaptic pruning and microglia-mediated changes in synaptic plasticity were observed both during brain development and in neurodegenerative diseases, stressing the key role of microglia-synapse interaction in these processes. Here we descried a technique for noninvasive in vivo monitoring of microglia-synapse interactions by means of two-photon microscopy.
Groundwater sustainability under land-use and land-cover changes
Publisher: Springer Science and Business Media LLC
Date: 03-2023
Maternal immune activation induces sustained changes in fetal microglia motility
Publisher: Springer Science and Business Media LLC
Date: 07-12-2020
DOI: 10.1038/S41598-020-78294-2
Abstract: Maternal infection or inflammation causes abnormalities in brain development associated with subsequent cognitive impairment and in an increased susceptibility to schizophrenia and autism spectrum disorders. Maternal immune activation (MIA) and increases in serum cytokine levels mediates this association via effects on the fetal brain, and microglia can respond to maternal immune status, but consensus on how microglia may respond is lacking and no-one has yet examined if microglial process motility is impaired. In this study we investigated how MIA induced at two different gestational ages affected microglial properties at different developmental stages. Immune activation in mid-pregnancy increased IL-6 expression in embryonic microglia, but failed to cause any marked changes in morphology either at E18 or postnatally. In contrast MIA, particularly when induced earlier (at E12), caused sustained alterations in the patterns of microglial process motility and behavioral deficits. Our research has identified an important microglial property that is altered by MIA and which may contribute to the underlying pathophysiological mechanisms linking maternal immune status to subsequent risks for cognitive disease.
Physiological Implications of Microglia–Synapse Interactions
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9658-2_6
Abstract: Microglia are the sole immune responding cells in the central nervous system. Their role as neuroimmune cells in the pathogenesis of various neurodegenerative and infectious diseases of the brain have been extensively studied. Upon brain disease and infection, they adopt an activated phenotype associated with the release of cytokines and neurotrophic factors and resulting in neuroprotective or neurotoxic outcomes. However, microglia are resident also in the healthy or physiological brain, but much less is known about their role(s) in the healthy brain, partly due to technical limitations regarding investigation of these highly reactive cells in the intact brain. Recent developments in molecular probes and in vivo optical imaging techniques has now helped to characterize microglia in the physiological or healthy brain. In vivo two-photon imaging of fluorescently labeled microglia have revealed that they are highly motile cells in the healthy brain, extending and retracting their processes that extend from a largely stationary cell soma. In this chapter, we briefly summarize some of the physiological functions of microglia in the uninjured brain, with a focus on interactions they have with synapses.
Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning
Publisher: Wiley
Date: 20-07-2023
DOI: 10.1002/GLIA.24441
Abstract: Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels and this adaptive myelination is associated with improved learning of motor tasks, suggesting such plasticity may enhance effective learning. In this study, we examined whether another aspect of myelin plasticity—changes in myelin lipid synthesis and composition—may also be associated with motor learning. We combined a motor learning task in mice with in vivo two‐photon imaging of neural activity in the primary motor cortex (M1) to distinguish early and late stages of learning and then probed levels of some key myelin lipids using mass spectrometry analysis. Sphingomyelin levels were elevated in the early stage of motor learning while galactosylceramide levels were elevated in the middle and late stages of motor learning, and these changes were correlated across in idual mice with both learning performance and neural activity changes. Targeted inhibition of oligodendrocyte‐specific galactosyltransferase expression, the enzyme that synthesizes myelin galactosylceramide, impaired motor learning. Our results suggest regulation of myelin lipid composition could be a novel facet of myelin adaptations associated with learning.
Holographic microscope and its biological application
Publisher: Elsevier BV
Date: 06-2022
Resting Microglia Directly Monitor the Functional State of SynapsesIn Vivoand Determine the Fate of Ischemic Terminals
Publisher: Society for Neuroscience
Date: 04-2009
DOI: 10.1523/JNEUROSCI.4363-08.2009
Abstract: Recent studies have identified the important contribution of glial cells to the plasticity of neuronal circuits. Resting microglia, the primary immune effector cells in the brain, dynamically extend and retract their processes as if actively surveying the microenvironment. However, just what is being s led by these resting microglial processes has not been demonstrated in vivo , and the nature and function of any interactions between microglia and neuronal circuits is incompletely understood. Using in vivo two-photon imaging of fluorescent-labeled neurons and microglia, we demonstrate that the resting microglial processes make brief (∼5 min) and direct contacts with neuronal synapses at a frequency of about once per hour. These contacts are activity-dependent, being reduced in frequency by reductions in neuronal activity. After transient cerebral ischemia, the duration of these microglia–synapse contacts are markedly prolonged (∼1 h) and are frequently followed by the disappearance of the presynaptic bouton. Our results demonstrate that at least part of the dynamic motility of resting microglial processes in vivo is directed toward synapses and propose that microglia vigilantly monitor and respond to the functional status of synapses. Furthermore, the striking finding that some synapses in the ischemic areas disappear after prolonged microglial contact suggests microglia contribute to the subsequent increased turnover of synaptic connections. Further understanding of the mechanisms involved in the microglial detection of the functional state of synapses, and of their role in remodeling neuronal circuits disrupted by ischemia, may lead to novel therapies for treating brain injury that target microglia.
Related Organisations
Isfahan University Of Technology
Location: Iran (Islamic Republic of)
Related Funding Activities
No related grants have been discovered for Hiroaki WAKE.