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INTRODUCTION: Down syndrome (DS) is a genetic cause of early‐onset Alzheimer's disease (AD). The National Institute on Aging–Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS. METHOD: Data are from the Alzheimer's Biomarker Consortium–Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [11C]Pittsburgh compound B) and tau (10 mCi of [18F]AV‐1451) were used to classify amyloid (A) –/+ and tau (T) +/–. Hippocampal volume classified neurodegeneration (N) –/+. The modified Cued Recall Test assessed episodic memory. RESULTS: Analyses included 162 adults with DS (aged M = 38.84 years, standard deviation = 8.41). Overall, 69.8% of participants were classified as A–/T–/(N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A–T–(N)– and A+T–(N)–. Tau PET (T+) most closely aligning with memory impairment and AD clinical status. DISCUSSION: Findings add to understanding of AT(N) biomarker profiles in DS. Highlights: Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)–/tau (T)–/neurodegeneration (N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+.The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology.Findings inform models for predicting the transition to the prodromal stage of AD in DS. [ABSTRACT FROM AUTHOR]

Background: The delay and increase in the number of Alzheimer's dementia patients cause many impacts, both from increased morbidity and moral and material losses. Biomarkers such as brain imaging (magnetic resonance imaging (MRI) and positron emission tomography (PET) Scan) need to be done immediately in the diagnosis of suspected Alzheimer's dementia. This study aimed to analyze the relationship between the hippocampal myo-inositol (MI)/ N-acetylaspartate (NAA) ratio and the severity of Mini-Mental State Examination (MMSE) in Alzheimer's dementia patients. Methods: MMSE and Hachinski scores were assessed by a neurologist, and the hippocampal mI/NAA ratio was calculated using MRI and MR spectroscopy. Results: The right hippocampal MI/NAA was significant with the incidence of Alzheimer's (p value = 0.018). Conclusion: There was a correlation between right MI/NAA and the severity of MMSE in Alzheimer's dementia patients. [ABSTRACT FROM AUTHOR]

Abstract Thousands of compounds are used and disposed of every day and many of them are not degraded in conventional treatment plants. It is necessary an alternative to eliminate these compounds. This can be done through electrooxidation technology, which was applied in this work to a mixture of pharmaceutical compounds including alprazolam (ALP), clonazepam (CLP), diazepam (DZP), lorazepam (LZP) and carbamazepine (CBZ) at 100 µg.L-1. The mixture was studied with different types of electrolytes and the neurotoxic effect of the treatment was evaluated. The best result was obtained with NaCl (0.5 g.L-1), leading to complete degradation of CLP, LZP and CBZ. [ABSTRACT FROM AUTHOR]

Abstract Thousands of compounds are used and disposed of every day and many of them are not degraded in conventional treatment plants. It is necessary an alternative to eliminate these compounds. This can be done through electrooxidation technology, which was applied in this work to a mixture of pharmaceutical compounds including alprazolam (ALP), clonazepam (CLP), diazepam (DZP), lorazepam (LZP) and carbamazepine (CBZ) at 100 µg.L-1. The mixture was studied with different types of electrolytes and the neurotoxic effect of the treatment was evaluated. The best result was obtained with NaCl (0.5 g.L-1), leading to complete degradation of CLP, LZP and CBZ. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of warming yang and supplementing kidney moxibustion therapy on the behavioristics and the expression levels of hippocampal IL-1β, TNF-α and NF-κB related genes and proteins of vascular dementia (VD) rats, and to explore the mechanism of warming yang and supplementing kidney moxibustion therapy in inhibiting VD inflammatory response. Methods Seventy-eight SD rats, except 10 rats as sham operation group (group A), were established into VD models by applying the ischemia reperfusion method in bilateral common carotid arteries. 30 models were successful and were randomly divided into model group (group B), moxibustion group (group C) and western medication group (group D), with 10 rats in each group. After modeling, suspended moxibustion was conducted at “Dàzhuī (大椎GV 14)”, “Mìngmén (命门GV 4)” and “Guānyuán (关元CV 4)” of the rats in group C for 15 min/time. The intervention was performed for once a day, and intervention for 4 consecutive weeks was needed. Intragastric administration with nimodipine (2 mg kg −1  d −1 ) was carried out in the rats in group D for 4 consecutive weeks. Morris water maze test was adopted for behavioral test in the rats in each group. HE staining was conducted in order to observe the pathological changes. RT-qPCR method and Western blot method were used for detecting the expression levels of hippocampal IL-1β, TNF-α and NF-κB related genes and proteins. Results After modeling, the Morris water maze escape latency of rats in operation groups was obviously longer than that in group A ( P  < 0.05). According to HE staining results, the arrangement of neurons in group B was incompact, the cell membranes were undefined, the cytoplasm was heterogeneous, karyopyknosis was found, the amount of necrosis increased, and the number of inflammatory cells significantly increased. Compared with group B, the number of inflammatory cells significantly reduced in group C and group D, and the amount of neuron necrosis also reduced. After intervention, compared with group B, the expression levels of TNF-α, p-IκB and NF-κBp65 mRNA in the hippocampal of the rats in group C and group D significantly decreased (all P  < 0.05), compared with group B, the expression levels of IL-1β, TNF-α and NF-κBp65 mRNA in the hippocampal of rats in group C and group D also significantly decreased (all P  < 0.05). Conclusion Warming yang and supplementing kidney moxibustion therapy may inhibit the NF-κB signaling pathway and reduce the inflammatory response through lowering the expression levels of IL-1β, TNF-α and NF-κB mRNA in the brain, thus achieving the purpose of treating VD. [ABSTRACT FROM AUTHOR]

Background: Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known.Hypothesis: A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia.Methods: Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, N = 10, age: 74.9 years, 7 women) or health education (HE, N = 16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus, and cornu ammonis were measured at baseline and at 24-month follow-up using 7-Tesla magnetic resonance imaging. Between-group volumetric differences at 24 months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities, and brain atrophy.Results: Between-group differences were significant for left hippocampus, left cornu ammonis, and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically nonsignificant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors.Conclusions: In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults. [ABSTRACT FROM AUTHOR]

Background: Sevoflurane is one of the most commonly used volatile anesthetics and it has been shown to induce widespread apoptotic neurodegeneration in aged rat. Calpain is also activated during apoptosis in several types of cells. We hypothesized that calpain resulted in apoptosis under long time sevoflurane exposure, and it might play a role in the sevoflurane-induced memory impairment in aged rats. Methods: Seventy-two 18-month-old male Sprague-Dawley rats were randomly divided into three groups ( n = 24): Control group rats were exposed to simply humid 50 % O balanced by N for 3 h; While M group rats received calpain inhibitor 10 mg/kg via the tail vein intravenously at 30 min before the animals inhaled 3 % sevoflurane for 3 h, subsequently received MDL 28170 3.33 mg/kg/h for 3 h. Sev group rats were only exposed to 3 % sevoflurane for 3 h without calpain inhibitor. Morris Water Maze was used to test the ability of learning and memory. Cytosolic calcium concentration was measured by using flow cytometry. Annexin-V labeled with a fluorophore or biotin can identify apoptotic cells by binding to PS. The expression of calpain in the hippocampus of rats was tested by Western blots. Results: The results showed that the M group had a shorter latency and had a larger number of times crossing over the previous platform site than that of the Sev group. Compared with Sev group, apoptosis rate and 76/80 kDa ratio of μ-calpain were significantly decreased in M group on the 1st day. Conclusions: Sevoflurane might induce apoptosis through increasing [Ca]c and the activity of μ-calpain, which might be identified at least partially the molecular mechanism by which sevoflurane induces apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Store operated Ca2+ entry (SOCE) replenishes intracellular Ca2+ stores and activates a number of intracellular signalling pathways. Whilst several molecular components forming store operated Ca2+ channels (SOCC) have been identified, their modulation in neurons remains poorly understood. Here, we extend on our previous findings and show that neuronal SOCE is modulated by tyrosine phosphorylation. Cyclopiazonic acid induced SOCE was characterised in hippocampal cultures derived from forebrain specific protein tyrosine phosphatase 1B knockout (PTP1B KO) mice and wild type (WT) litter mates using Fura-2 Ca2+ imaging. PTP1B KO cultures expressed elevated SOCE relative to WT cultures without changes in cytoplasmic Ca2+ homeostasis or depolarisation-induced Ca2+ influx. WT and PTP1B KO cultures displayed similar pharmacological sensitivities towards the SOCE inhibitors gadolinium and 2-aminoethoxydiphenyl borate, as well as the tyrosine kinase inhibitor Ag126 indicating an augmentation of native SOCCs by PTP1B. Following store depletion WT culture homogenates showed heightened phospho-tyrosine levels, an increase in Src tyrosine kinase activation and two minor PTP1B species. These data suggest tyrosine phosphorylation gating SOCE, and implicate PTP1B as a key regulatory enzyme. The involvement of PTP1B in SOCE and its relation to SOCC components and mechanism of regulation are discussed. [Copyright &y& Elsevier]

Introduction: Neurotoxic homocysteine (Hcy) is thought to be an independent risk factor for neurodegenerative diseases, including Alzheimer's disease. This study is to determine whether HT22 cells, a murine hippocampal neuronal model, can be used as an in vitro model, besides the primary neuronal cultures, to investigate the effects of Hcy. Materials and methods: MTS assay and Hoechst 33342/propidium iodide discrimination were used to assess the cell viability and cell death on undifferentiated and differentiated HT22 cells. Semi-quantitative reverse transcription polymerase chain reaction and western blot were used to determine the expression of N-methyl D-aspartate (NMDA) receptor. Results: We found that undifferentiated and differentiated HT22 cells responded to Hcy toxicity differentially, with the undifferentiated cells resistant while the differentiated cells sensitive. The underlying mechanism appeared to be the differential expression levels of NMDA glutamate receptor between the undifferentiated and differentiated cells. Similar to what have been observed in primary neuronal cultures, the Hcy toxicity in the differentiated HT22 cells was largely attenuated by NMDA receptor antagonists, MK-801 and memantine. Conclusion: These results suggest for the first time that the differentiation of HT22 cells could induce the expression of NMDA receptors, which lead to Hcy mediate concentration-dependent apoptosis-necrotic continuum of HT22 cell death. The differentiation status of the HT22 cells is important for modeling neurons in vitro, with the differentiated HT22 neurons resembling more characteristics of primary hippocampal neurons while the undifferentiated HT22 cells being proliferating neuronal precursor cells. The differentiated HT22 neurons can be used as a platform to study Hcy toxicity. [ABSTRACT FROM AUTHOR]