Activation of 5-HT 1b/d receptor restores the cognitive function by reducing glutamate release, deposition of β-amyloid and TLR-4 pathway in the brain of scopolamine-induced dementia in rat

Abstract

Objectives This study evaluates the effect of 5-HT 1b/d agonist on cognitive function in scopolamine (SPN)-induced dementia in the rat. Methods Dementia was induced by administration of SPN 2 mg/kg/day, intraperitoneally, for a duration of 21 days. The effect of zolmitriptan (ZMT) 30 mg/kg, intraperitoneally, was observed on cognitive function, and the parameters of oxidative stress like malondialdehyde (MDA) level, nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were estimated at the end. Histopathology study of brain tissue was performed for the determination of β-amyloid peptide, and qRT-PCR was used to determine the mRNA expression of Toll-like receptor 4 (TLR-4), IL-17 and β-amyloid. Key findings Data of the study suggested that treatment with ZMT alone and in combination with DMP (dextromethorphan) significantly (P < 0.01) decreases the escape latency in conditioned avoidance response (CAR) and transfer latency in elevated plus maze (EPM) as compared with negative control group. Moreover, the result of Morris water maze (MWM) shows an increase in retention time and a decrease in escape latency in ZMT alone and in combination with DMP-treated group of SPN-induced dementia than in the negative control group. There was a significant decrease in MDA and NO and increase in SOD and GPX in the brain tissues of ZMT and ZMT + DMP-treated group than negative control group. Histopathology study also suggested that the concentration of Aβ peptide decreases in the brain tissues in ZMT and ZMT + DMP-treated group than the negative control group. Moreover, ZMT treatment ameliorates the altered mRNA expression of TLR-4 and IL-17 in the brain tissue of SPN-induced dementia rat. Conclusions In conclusion, ZMT restores the cognitive functions and impaired memory in SPN-induced dementia in the rat by decreasing oxidative stress and Aβ peptide in the brain tissue of rat.

Beneficial effect of 5‐HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α‐synuclein

“…All rats were separated into six groups and treated as follows: Group 1: control, Group 2: negative control [Parkinson's was induced in all the animals by the administration of reserpine 5 mg/kg ip for the duration of 3 days], Group 3/ZLM group: PD animals + ZLM 30 mg/kg ip for 4 days after the induction of PD; Group 4/STD group: PD animals + levodopa and carbidopa (200 + 5 mg/kg ip) for 4 days after the induction of PD; Group 5/ZLM + GA group: PD animals + ZLM 30 mg/kg ip + GA 1.5 mg/kg; and Group 6/ZLM + DX group: PD animals + ZLM (30 mg/kg ip) + DX (20 mg/kg ip) for 4 days after the induction of PD. [ 6 ] Body weight estimations and behavioral studies were performed at the end of the protocol.…”

“…Moreover, ZLM is reported for analgesic property and beneficial effect against neurodegeneration and cocaine dependance. [ 6 ] Thus, the reported study focus on the role of the 5‐HT1b/1d receptor in PD.…”

Acupoint catgut embedding improves learning and memory impairment in vascular dementia rats

“…TLRs are receptors that mainly recognize pathogenic microorganisms in the natural immune system. When cerebral ischemia occurs, TLRs are activated, sending signals to trigger inflammatory reactions, and an abundance proinflammatory cytokines and adhesion factors are expressed, leading to brain tissue damage (27)(28)(29). There are many classifications of TLRs, among which TLR4 distributed on the cell surface can be expressed by vascular smooth muscle cells and endothelial cells in the brain, which can stimulate the secretion of inflammatory substances, and participate in and mediate inflammatory injury (30,31).…”

Ginsenosides affect the system of Toll-like receptors in the brain of rats under conditions of long-term alcohol withdrawal

“…Toll-like receptor, TLR) опосредуют развитие нейровоспаления в структурах головного мозга при длительном употреблении этанола [16][17][18]. Имеются сведения, что TLR-сигнализация не только способствует развитию нейровоспаления в головном мозге, но может быть вовлечена в механизмы регуляции функциональной активности нейромедиаторных систем [22][23][24], внося определённый вклад в формирование патологического влечения к алкоголю.…”