Alzheimer’s disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy.

中文翻译：

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S100A9蛋白聚集增强海马谷氨酸修饰单胺能神经化学：谷氨酸抗体敏感性结果对阿尔茨海默氏样记忆下降。

阿尔茨海默氏病（AD）涉及痴呆症，可能是由综合性炎症过程，淀粉样蛋白生成和神经元凋亡引起的。谷氨酸还可以通过兴奋性毒性引起神经元死亡，这与某些神经系统疾病类似。目的是检查单独使用体外产生的促炎蛋白S100A9聚集物种或谷氨酸抗体（Glu-Abs）对12个月大小鼠的Morris水迷宫（MWM）空间学习和记忆性能的治疗。同时监测氨基酸和单胺类脑神经递质的代谢变化。最初，通过原子力显微镜和硫黄素T测定法对S100A9原纤维进行了形态学验证。然后将它们单独鼻内给药或与Glu-Ab一起给药14天，然后进行5天MWM方案，然后进行海马和前额叶皮层神经化学分析。S100A9引起诱发的空间性失忆，这与谷氨酸和多巴胺能神经化学破坏有关。随后，Glu-Abs降低了海马谷氨酸的释放，DOPAC和HVA的升高以及DOPAC / DA和HVA / DA的比率，同时防止了空间记忆不足。目前的结果强调了S100A9纤维状聚集体的致病性，其引起与衰老的大脑中海马谷氨酸释放增强和DA-能级破坏有关的空间记忆失忆。通过神经保护策略可以在痴呆症治疗期间利用这一发现。S100A9引起诱发的空间性失忆，这与谷氨酸和多巴胺能神经化学破坏有关。随后，Glu-Abs降低了海马谷氨酸的释放，DOPAC和HVA的升高以及DOPAC / DA和HVA / DA的比率，同时防止了空间记忆不足。目前的结果强调了S100A9纤维状聚集体的致病性，其引起与衰老的脑中海马谷氨酸释放增强和DA-能级破坏有关的空间记忆失忆。通过神经保护策略可以在痴呆症治疗期间利用这一发现。S100A9引起诱发的空间性失忆，这与谷氨酸和多巴胺能神经化学破坏有关。随后，Glu-Abs降低了海马谷氨酸的释放，DOPAC和HVA的升高以及DOPAC / DA和HVA / DA的比率，同时防止了空间记忆不足。目前的结果强调了S100A9纤维状聚集体的致病性，其引起与衰老的大脑中海马谷氨酸释放增强和DA-能级破坏有关的空间记忆失忆。通过神经保护策略可以在痴呆症治疗期间利用这一发现。随后通过Glu-Abs降低了DOPAC / DA和HVA / DA的比率，同时防止了空间记忆不足。目前的结果强调了S100A9纤维状聚集体的致病性，其引起与衰老的脑中海马谷氨酸释放增强和DA-能级破坏有关的空间记忆失忆。通过神经保护策略可以在痴呆症治疗期间利用这一发现。随后通过Glu-Abs降低了DOPAC / DA和HVA / DA的比率，同时防止了空间记忆不足。目前的结果强调了S100A9纤维状聚集体的致病性，其引起与衰老的大脑中海马谷氨酸释放增强和DA-能级破坏有关的空间记忆失忆。通过神经保护策略可以在痴呆症治疗期间利用这一发现。