Modality-Specific Impairment of Hippocampal CA1 Neurons of Alzheimer’s Disease Model Mice

Impairment of episodic memory, a class of memory for spatiotemporal context of an event, is an early symptom of Alzheimer's disease. Both spatial and temporal information are encoded and represented in the hippocampal neurons, but how these representations are impaired under amyloid β (Aβ) pathology remains elusive. We performed chronic imaging of the hippocampus in awake male amyloid precursor protein (App) knock-in mice behaving in a virtual reality environment to simultaneously monitor spatiotemporal representations and the progression of Aβ depositions. We found that temporal representation is preserved, while spatial representation is significantly impaired in the App knock-in mice. This is due to the overall reduction of active place cells but not time cells, and compensatory hyperactivation of remaining place cells near Aβ aggregates. These results indicate the differential impact of Aβ aggregates on two major modalities of episodic memory, suggesting different mechanisms for forming and maintaining these two representations in hippocampus.SIGNIFICANCE STATEMENT:Spatiotemporal memory impairments are common at the early stage of Alzheimer's disease patients. We demonstrate the different impairment patterns of place and time cells in the dorsal hippocampus of head-fixed App knock-in mouse by in vivo two-photon calcium imaging over months under the virtual reality spatiotemporal tasks. These results highlight that place cells were preferentially and gradually damaged nearby Aβ aggregates, while time cells were less vulnerable. We further show these impairments were due to neuronal hyperactivity that occurs near the Aβ deposition. We suggest the differential and gradual impairment in two major modalities of episodic memory under Aβ pathology

ロボットによる未知の紐の動的マニピュレーション

金沢大学理工研究域フロンティア工学系布団を敷く、衣服をたたむなど、柔軟物を動的に扱えるロボットに対するニーズが高まっている。柔軟物は様々な特性を有しており、さらに動きの中で形状が変化してしまうため、操作が困難である。そこで本研究は、その初期研究として、ロボットによる未知の紐の動的マニピュレーションの実現を目指している。シミュレーションとカメラで捉えた紐の動きをもとに、紐のモデルのパラメータを推定し、紐の操りに応用する。It is difficult for a robot to manipulate flexible objects because the deformations of their shapes make motion planning difficult. In this paper, we propose a concept of manipulating unknown string dexterously by robot arm. A string is described as the three-dimensional model that is composed a number of masses, springs, dampers, hinge springs, and hinge dampers. After parameters of this model are estimated by the comparison between actual string motion and motion simulation using the model with various parameters, robot motion to manipulate the string for realizing task is planned using the model with estimated parameters.出版者照会後に全文公

Post-treatment with JP-1302 protects against renal ischemia/reperfusion-induced acute kidney injury in rats

Ischemia/reperfusion injury is the most common cause of acute kidney injury. We previously revealed that pre-treatment with yohimbine or JP-1302 attenuated renal ischemia/reperfusion injury by inhibition of α2C-adrenoceptor antagonist. The aim of the present study is to investigate the effects of post-treatment with JP-1302 on renal ischemia/reperfusion injury in rats. Male Sprague Dawley rats were randomly divided into four groups: sham operation, ischemia/reperfusion, pre-treatment with JP-1302 (3.0 mg/kg) and post-treatment with JP-1302 groups. In ischemia/reperfusion injury, renal functional parameters, such as blood urea nitrogen, plasma creatinine and creatinine clearance, deteriorated after reperfusion. Renal venous norepinephrine concentrations, as well as inflammatory molecules in the kidney increased after reperfusion. Both pre- and post-treatment with JP-1302 improved renal dysfunction, tissue damage, renal venous norepinephrine concentrations and inflammatory molecules expression in the kidney. In conclusion, these results suggest that post-treatment with JP-1302 protects on ischemia/reperfusion-induced acute kidney injury by suppressing cytokine upregulation via α2C-adrenoceptors. Keywords: JP-1302, Ischemia/reperfusion, Acute kidney injury, α2C-adrenoceptor, Norepinephrin

M‐PAST score is better than MAST score for the diagnosis of active fibrotic nonalcoholic steatohepatitis

BackgroundClinical trials enroll patients with active fibrotic nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease [NAFLD] activity score ≥ 4) and significant fibrosis (F ≥ 2); however, screening failure rates are high following biopsy. We developed new scores to identify active fibrotic NASH using FibroScan and magnetic resonance imaging (MRI).MethodsWe undertook prospective primary (n = 176), retrospective validation (n = 169), and University of California San Diego (UCSD; n = 234) studies of liver biopsy-proven NAFLD. Liver stiffness measurement (LSM) using FibroScan or magnetic resonance elastography (MRE), controlled attenuation parameter (CAP), or proton density fat fraction (PDFF), and aspartate aminotransferase (AST) were combined to develop a two-step strategy-FibroScan-based LSM followed by CAP with AST (F-CAST) and MRE-based LSM followed by PDFF with AST (M-PAST)-and compared with FibroScan-AST (FAST) and MRI-AST (MAST) for diagnosing active fibrotic NASH. Each model was categorized using rule-in and rule-out criteria.ResultsAreas under receiver operating characteristic curves (AUROCs) of F-CAST (0.826) and M-PAST (0.832) were significantly higher than those of FAST (0.744, p = 0.004) and MAST (0.710, p < 0.001). Following the rule-in criteria, positive predictive values of F-CAST (81.8%) and M-PAST (81.8%) were higher than those of FAST (73.5%) and MAST (70.0%). Following the rule-out criteria, negative predictive values of F-CAST (90.5%) and M-PAST (90.9%) were higher than those of FAST (84.0%) and MAST (73.9%). In the validation and UCSD cohorts, AUROCs did not differ significantly between F-CAST and FAST, but M-PAST had a higher diagnostic performance than MAST.ConclusionsThe two-step strategy, especially M-PAST, showed reliability of rule-in/-out for active fibrotic NASH, with better predictive performance compared with MAST. This study is registered with ClinicalTrials.gov (number, UMIN000012757)