PDF(Pubmed)
Abstract：
UNASSIGNED: Repurposing dantrolene to treat Alzheimer\'s disease has been shown to be effective in amyloid transgenic mouse models but has not been examined in a model of tauopathy.
UNASSIGNED: The effects of a nanoparticle intranasal formulation, the Eagle Research Formulation of Ryanodex (ERFR), in young adult and aged wild type and PS19 tau transgenic mice was investigated.
UNASSIGNED: The bioavailability of intranasal ERFR was measured in 2 and 9-11-month-old C57BL/6J mice. Blood and brain samples were collected 20 minutes after a single ERFR dose, and the plasma and brain concentrations were analyzed. Baseline behavior was assessed in untreated PS19 tau transgenic mice at 6 and 9 months of age. PS19 mice were treated with intranasal ERFR, with or without acrolein (to potentiate cognitive dysfunction), for 3 months, beginning at 2 months of age. Animal behavior was examined, including cognition (cued and contextual fear conditioning, y-maze), motor function (rotarod), and olfaction (buried food test).
UNASSIGNED: The dantrolene concentration in the blood and brain decreased with age, with the decrease greater in the blood resulting in a higher brain to blood concentration ratio. The behavioral assays showed no significant changes in cognition, olfaction, or motor function in the PS19 mice compared to controls after chronic treatment with intranasal ERFR, even with acrolein.
UNASSIGNED: Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice.
UNASSIGNED: The effects of a nanoparticle intranasal formulation, the Eagle Research Formulation of Ryanodex (ERFR), in young adult and aged wild type and PS19 tau transgenic mice was investigated.
UNASSIGNED: The bioavailability of intranasal ERFR was measured in 2 and 9-11-month-old C57BL/6J mice. Blood and brain samples were collected 20 minutes after a single ERFR dose, and the plasma and brain concentrations were analyzed. Baseline behavior was assessed in untreated PS19 tau transgenic mice at 6 and 9 months of age. PS19 mice were treated with intranasal ERFR, with or without acrolein (to potentiate cognitive dysfunction), for 3 months, beginning at 2 months of age. Animal behavior was examined, including cognition (cued and contextual fear conditioning, y-maze), motor function (rotarod), and olfaction (buried food test).
UNASSIGNED: The dantrolene concentration in the blood and brain decreased with age, with the decrease greater in the blood resulting in a higher brain to blood concentration ratio. The behavioral assays showed no significant changes in cognition, olfaction, or motor function in the PS19 mice compared to controls after chronic treatment with intranasal ERFR, even with acrolein.
UNASSIGNED: Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice.
摘要：
■在淀粉样蛋白转基因小鼠模型中已证明丹曲林用于治疗阿尔茨海默病有效，但尚未在tau蛋白病模型中进行检查。
■纳米颗粒鼻内制剂的效果，鹰研究Ryanodex配方(ERFR)，在年轻的成年和老年野生型和PS19tau转基因小鼠中进行了研究。
■在2和9-11个月大的C57BL/6J小鼠中测量鼻内ERFR的生物利用度。在单次ERFR剂量后20分钟收集血液和脑样本，并分析了血浆和脑浓度。在6和9月龄未处理的PS19tau转基因小鼠中评估基线行为。PS19小鼠用鼻内ERFR治疗，有或没有丙烯醛（加强认知功能障碍），三个月,从2个月大开始。检查动物行为，包括认知(暗示和上下文恐惧条件，y-迷宫)，运动功能（旋转杆），和嗅觉（掩埋食物测试）。
■随着年龄的增长，血液和大脑中的丹曲林浓度降低，随着血液中的减少更大，导致更高的大脑与血液浓度比。行为分析显示认知没有显著变化，嗅觉,或PS19小鼠的运动功能，与鼻内ERFR慢性治疗后的对照组相比，即使是丙烯醛。
■我们的研究表明，鼻内给药ERFR在老年小鼠脑中的浓度高于血液中的浓度，并且在长期使用PS19小鼠中没有严重的全身性副作用。
■纳米颗粒鼻内制剂的效果，鹰研究Ryanodex配方(ERFR)，在年轻的成年和老年野生型和PS19tau转基因小鼠中进行了研究。
■在2和9-11个月大的C57BL/6J小鼠中测量鼻内ERFR的生物利用度。在单次ERFR剂量后20分钟收集血液和脑样本，并分析了血浆和脑浓度。在6和9月龄未处理的PS19tau转基因小鼠中评估基线行为。PS19小鼠用鼻内ERFR治疗，有或没有丙烯醛（加强认知功能障碍），三个月,从2个月大开始。检查动物行为，包括认知(暗示和上下文恐惧条件，y-迷宫)，运动功能（旋转杆），和嗅觉（掩埋食物测试）。
■随着年龄的增长，血液和大脑中的丹曲林浓度降低，随着血液中的减少更大，导致更高的大脑与血液浓度比。行为分析显示认知没有显著变化，嗅觉,或PS19小鼠的运动功能，与鼻内ERFR慢性治疗后的对照组相比，即使是丙烯醛。
■我们的研究表明，鼻内给药ERFR在老年小鼠脑中的浓度高于血液中的浓度，并且在长期使用PS19小鼠中没有严重的全身性副作用。
