![]() In addition, electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that (D-Ser2) Oxm increased the power of the theta rhythm. In this study, we showed that 2 weeks of intraperitoneal administration of (D-Ser2) Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer's disease model mice. However, the protective mechanism remains unclear. Additionally, we have demonstrated that (D-Ser2) Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer's disease model mice. In our previous studies, we have shown that (D-Ser2) oxyntomodulin (Oxm), a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide, protects hippocampal neurons against Aß1-42-induced cytotoxicity, and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons. , Antagonistas dos Receptores de Orexina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico These results indicate that the detrimental effects of SB-334867 on cognitive behaviors in 3xTg-AD mice are closely related to the decrease of PSD-95 and depression of in vivo long-term potentiation (LTP) caused by increased Aß oligomers and p-tau. The results showed that chronic OX1R blockade aggravated the impairments of short-term working memory, long-term spatial memory and synaptic plasticity in 9-month-old female 3xTg-AD mice, increased levels of soluble Aß oligomers and p-tau, and decreased PSD-95 expression in the hippocampus of 3xTg-AD mice. Then, different behavioral tests were performed to observe the effects of OX1R blockade on cognitive function of 3xTg-AD mice exhibited both Aß and tau pathology, in vivo electrophysiological recording and western blot were used to investigate the potential mechanism. In the present study, selective OX1R antagonist SB-334867 was used to block OX1R. Considering that OX1R is highly expressed in the hippocampus and plays important roles in learning and memory, the effects of OX1R in AD cognitive dysfunction and its possible mechanism should be investigated. ![]() Furthermore, recent research found that dual orexin receptor (OXR) antagonist might affect Aß level and cognitive dysfunction in AD, but the effects of OX1R or OX2R alone is unreported until now. Previous research found that elevated orexin level in the cerebrospinal fluid was closely related to the course of AD, and orexin-A treatment could increase amyloid ß protein (Aß) deposition and aggravate spatial memory impairment in APP/PS1 mice. , Precursor de Proteína beta-Amiloide/metabolismoĬognitive dysfunction is the main clinical manifestation of Alzheimer's disease (AD). , Ácido Aspártico Endopeptidases/metabolismo ![]() , Secretases da Proteína Precursora do Amiloide/metabolismo These results indicated that OXA aggravates cognitive deficits and hippocampal synaptic plasticity impairment in 3xTg-AD mice by increasing Aß production and decreasing Aß clearance through disruption of the circadian rhythm and sleep-wake cycle. The results showed that OXA aggravated memory impairments and circadian rhythm disturbance, exacerbated hippocampal LTP depression, and increased Aß and tau pathologies in 3xTg-AD mice by affecting BACE1 and NEP expression. In the present study, the effects of OXA on cognitive functions, synaptic plasticity, Aß levels, tau hyperphosphorylation, BACE1 and NEP expression, and circadian locomotor rhythm were evaluated. Furthermore, the potential electrophysiological mechanism by which OXA affects cognitive deficits and the molecular mechanism by which OXA increases amyloid ß (Aß) levels are unknown. However, the effects of OXA on other types of cognitive deficits, especially in 3xTg-AD mice exhibiting both plaque and tangle pathologies, have not been reported. ![]() Orexin has recently been linked to AD pathogenesis, and exogenous orexin-A (OXA) aggravates spatial memory impairment in APP/PS1 mice. Dementia is the main clinical feature of Alzheimer's disease (AD).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |