Hippocampal hyperphosphorylated tau-induced deficiency is rescued by L-type calcium channel blockade.

Aging and Alzheimer's disease are associated with chronic elevations in neuronal calcium influx via L-type calcium channels. The hippocampus, a primary memory encoding structure in the brain, is more vulnerable to calcium dysregulation in Alzheimer's disease. Recent research has suggested a link between L-type calcium channels and tau hyperphosphorylation. However, the precise mechanism of L-type calcium channel-mediated tau toxicity is not understood. In this study, we seeded a human tau pseudophosphorylated at 14 amino acid sites in rat hippocampal cornu ammonis 1 region to mimic soluble pretangle tau. Impaired spatial learning was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats as early as 1-3 months and worsened at 9-10 months post-infusion. Rats infused with wild-type human tau exhibited milder behavioural deficiency only at 9-10 months post-infusion. No tangles or plaques were observed in all time points examined in both human tau pseudophosphorylated at 14 amino acid sites and human tau-infused brains. However, human tau pseudophosphorylated at 14 amino acid sites-infused hippocampus exhibited a higher amount of tau phosphorylation at S262 and S356 than the human tau-infused rats at 3 months post-infusion, paralleling the behavioural deficiency observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Neuroinflammation indexed by increased Iba1 in the cornu ammonis 1 was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 but not 9 months post-infusion. Spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 months post-infusion was paralleled by decreased neuronal excitability, impaired NMDA receptor-dependent long-term potentiation and augmented L-type calcium channel-dependent long-term potentiation at the cornu ammonis 1 synapses. L-type calcium channel expression was elevated in the soma of the cornu ammonis 1 neurons in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Chronic L-type calcium channel blockade with nimodipine injections for 6 weeks normalized neuronal excitability and synaptic plasticity and rescued spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats. The early onset of L-type calcium channel-mediated pretangle tau pathology and rectification by nimodipine in our model have significant implications for preclinical Alzheimer's disease prevention and intervention.

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in Central India - Will it work?

OBJECTIVE: To determine whether the OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA) in sputum is a valid tool for HIV surveillance among TB patients. METHODS: A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis. Sputa were tested for antibodies to HIV using OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA). The results were compared with results of serum ELISA. RESULTS: Compared to serum ELISA, the OraQuick® HIV-1/2 Assay in sputum specimens reported 90% sensitivity (9/10) and 100% specificity (307/307), with a positive predictive value of 100% (95%CI: 66.37%-100.00%) and a negative predictive value of 99.68% (95%CI: 98.20%-99.99%). CONCLUSIONS: This testing method may provide a useful strategy for conducting HIV surveillance in possible co-infected TB patients at peripheral centres. Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with low HIV endemicity.