Your search for: 'author:("Hisatsune, Tatsuhiro")' has returned 3 results. (0.011s) Save search

Authors: Matsuda, Takeshi | Hisatsune, Tatsuhiro

Article Type: Research Article

Abstract: We previously reported that neuroinflammation contributes to the amnesia of AβPPswe/PSEN1dE9 Alzheimer’s disease model mice fed a high-fat diet to induce type-2 diabetes (T2DM-AD mice), but the underlying mechanism for the memory decline remained unclear. Recent studies have suggested that cholinergic modulation is involved in neuroinflammatory cellular reactions including neurogenesis and gliosis, and in memory improvement. In this study, we administered a broad-spectrum cholinesterase inhibitor, rivastigmine (2 mg/kg/day, s.c.), into T2DM-AD mice for 6 weeks, and evaluated their memory performance, neurogenesis, and neuroinflammatory reactions. By two hippocampal-dependent memory tests, the Morris water maze and contextual fear conditioning, rivastigmine improved the memory …deterioration of the T2DM-AD mice (n  = 8, p  < 0.01). The number of newborn neurons in the hippocampal dentate gyrus was 1138±324 (Ave±SEM) in wild-type littermates, 2573±442 in T2DM-AD-Vehicle, and 2165±300 in T2DM-AD-Rivastigmine mice, indicating that neurogenesis was accelerated in the two T2DM-AD groups (n  = 5, p  < 0.05). The dendritic maturation of new neurons in T2DM-AD-Vehicle mice was severely abrogated, and rivastigmine treatment reversed this retarded maturation. In addition, the hippocampus of T2DM-AD-Vehicle mice showed increased proinflammatory cytokines IL-1β and TNF-α and gliosis, and rivastigmine treatment blocked these inflammatory reactions. Rivastigmine did not change the insulin abnormality or amyloid pathology in these mice. Thus, cholinergic modulation by rivastigmine treatment led to enhanced neurogenesis and the suppression of gliosis, which together ameliorated the memory decline in T2DM-AD model mice. Show more

Keywords: Acetylcholinesterase, Alzheimer’s disease, gliosis, high-fat diet, inflammation, memory, neurogenesis, rivastigmine, type 2 diabetes mellitus

DOI: 10.3233/JAD-160761

Citation: Journal of Alzheimer's Disease, vol. 56, no. 1, pp. 1-23, 2017

Authors: Herculano, Bruno | Tamura, Minami | Ohba, Ayaka | Shimatani, Mayu | Kutsuna, Natsumaro | Hisatsune, Tatsuhiro

Article Type: Research Article

Abstract: Our goal in this study was to determine whether or not feeding young (4 months old) Alzheimer's disease model transgenic mice with a high fat diet (HFD), consisting of 32% fat, is capable of causing cognitive decline and whether treatment with β-alanyl-L-histidine (carnosine) is capable of reducing these effects. Carnosine is an endogenous antioxidant and antiglycating agent that is abundantly present in the brain and muscle tissues of vertebrates. After 8 weeks of feeding with HFD, we observed a significant decline in the contextual memory in transgenic mice fed with HFD as compared to transgenic mice fed with a normal …diet as well as to normal diet-wild type mice. Treatment with carnosine at a dose of 5 mg/day for 6 weeks was effective in preventing cognitive decline, as the transgenic group fed with HFD and treated with carnosine displayed a level of cognition comparable to controls. No differences in senile plaque load were observed between all groups. However, we observed an increase in the expression of RAGE in blood vessels as well as increased microglial activation in the hippocampus of animals fed with HFD, effects that were reversed when treated with carnosine. Given these results, there is a possibility that inflammation and cerebrovascular abnormalities might be the cause of cognitive decline in this model. Show more

Keywords: Alzheimer's disease, carnosine, high fat diet, oxidative stress

DOI: 10.3233/JAD-2012-121324

Citation: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 983-997, 2013

Authors: Hisatsune, Tatsuhiro | Kaneko, Jun | Kurashige, Hiroki | Cao, Yuan | Satsu, Hideo | Totsuka, Mamoru | Katakura, Yoshinori | Imabayashi, Etsuko | Matsuda, Hiroshi

Article Type: Research Article

Abstract: Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60–78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the …ACS group, compared to the placebo group (p  = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p  = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p  = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed. Show more

Keywords: Alzheimer’s disease, anserine and carnosine, cognitive function, dementia, elderly people, inflammatory cytokine, perfusion MRI, randomized controlled trial, verbal memory

DOI: 10.3233/JAD-150767

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 149-159, 2016