Ueno H.,Okayama University |
Suemitsu S.,Kawasaki Medical University |
Matsumoto Y.,Okayama University |
Okamoto M.,Okayama University
Neural Plasticity | Year: 2015
Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity. © 2015 Hiroshi Ueno et al.
Miwa K.,Osaka University |
Tanaka M.,Stroke Center |
Okazaki S.,Osaka University |
Yagita Y.,Kawasaki Medical University |
And 3 more authors.
Journal of Alzheimer's Disease | Year: 2015
Background: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia. Objective: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors. Methods:Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 εmol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia. Results: In the 643 subjects (age: 67.2±8.4 years, male: 59%; education: 12.9±2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE ε4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant. Conclusions: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk. © 2016 - IOS Press and the authors.
Okabe N.,Kagawa University |
Nakamura T.,Kagawa University |
Toyoshima T.,Kagawa University |
Miyamoto O.,Kawasaki Medical University |
And 2 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2011
Previous studies have demonstrated that the generation of reactive oxygen species and an excessive inflammatory reaction are involved in the progression of neural damage following brain ischemia. In this study, we focused on the anti-inflammatory and antioxidant properties of eicosapentaenoic acid (EPA). Gerbils were treated intraperitoneally with 500 mg/kg of EPA ethyl for 4 weeks until the day of forebrain ischemia, which was induced by occluding the bilateral common carotid artery for 5 minutes. In the first part of the 2-part experiment, the effect of EPA treatment was evaluated using hematoxylin and eosin staining and deoxynucleotidyl transferase-mediated dUTP nick-end labeling as a marker of cell death (n = 3 per group). The inflammatory reaction was evaluated using anti-Iba1 immunohistochemistry, a marker of microglial activation (n = 3 per group), and detection of 8-hydroxyl-2′- deoxyguanosine, a marker of oxidative DNA damage (n = 4 per group). In the second part of the experiment, the effect of EPA treatment on memory function was examined using an 8-arm radial maze (n = 6 per group). EPA treatment significantly inhibited DNA oxidative damage (P < .05) and accumulation of Iba1-positive cells in the CA1 area at 12 and 72 hours after the induction of ischemia, and also decreased apoptotic neurons and neuronal death (P < .001) at 72 hours after ischemia. EPA treatment also significantly improved memory function (P < .05). These findings suggest that EPA inhibits the inflammatory reaction and oxidative damage occurring after ischemic brain injury, and also may contribute to the prevention of neural damage and memory impairment following such injury. © 2011 by National Stroke Association.
Le N.A.,Kanazawa University |
Katsuyama M.,Kanazawa University |
Demura M.,Kanazawa University |
Tanii H.,Kanazawa University |
And 2 more authors.
Environmental Health and Preventive Medicine | Year: 2014
Objectives: Serine protease inhibitor Kazal type-5 (SPINK5) plays a crucial role in deciding the timing of desquamation of the skin. Its gene expression is limited at the very surface of the stratum granulosum (SG), whereas expression of kallikreins (KLKs) encoding proteases is usually found throughout the stratum spinosum and SG. Methods: To explore the difference in expression regulation of these proteases/inhibitors, the function of SPINK5 promoter was examined using luciferase assay. Results: Luciferase assay targeting the SPINK5 promoters (nucleotide -676/-532 and -318/-146 from the major transcription start site) showed high intensity in NHEK human keratinocyte. These two sites had neither common cis-elements nor GATA3 element but electrophoretic mobility shift assay showed similar retardation bands. Moreover, DNA footprinting did not display specific protected bands. Thus, we could not identify cis-element(s) that controlled these elements. Differentiation induced by high Ca2+ medium failed to alter their luciferase activities. Transfection of GATA3 expressing vector significantly but slightly increased them and that of vector expressing its dominant negative form decreased. Conclusions: Although GATA3 is reportedly important for inhibition of proliferation and induction of differentiation of keratinocytes, its effect on SPINK5 expression was indirect and GATA3 alone was insufficient for final differentiation of keratinocytes where full SPINK5 expression was observed. © 2014 The Author(s).
Lu F.,Kagawa University |
Nakamura T.,Kagawa University |
Toyoshima T.,Kagawa University |
Liu Y.,Kagawa University |
And 7 more authors.
Brain Research | Year: 2014
The present study investigates the potential protective effects of granulocyte colony-stimulating factor (G-CSF) and underlying mechanisms in a gerbil model of global cerebral ischemia. We examined neuronal death, inflammatory reaction and neurogenesis in hippocampus 72 h after transient forebrain ischemia and investigated functional deficits. G-CSF was administered intraperitoneally 24 h before ischemia and then daily. Treatment with G-CSF at 25-50 μg/kg significantly reduced neuronal loss in the hippocampus CA1 area but not at 10 ug/kg. G-CSF at 50 μg/kg significantly decreased the level of TNF-α, the number of Iba1 (microglia marker) positive cells and reduced locomotor activity 72 h after transient forebrain ischemia. Furthermore, the number of DCX-positive cells in the hippocampal dentate gyrus increased in with G-CSF treatment. Our findings indicate that G-CSF reduces hippocampal neuronal cell death dose-dependently and attenuates sensorimotor deficits after transient forebrain ischemia. These neuroprotective effects of G-CSF may be linked to inhibition of inflammation and possibly increased neurogenesis in the hippocampus. © 2013 Elsevier B.V. All rights reserved.