Exploring the neuroprotective effects and mechanisms of pituitary adenylate cyclase-activating polypeptides in Parkinson's disease animal models

Autor: Pei Lijuan, Tian Hongzhan, Li Rui, TianTing, Zhang Min, Cai Hongbin
Jazyk: čínština
Rok vydání: 2024
Předmět:
Zdroj: 生物医学转化, Vol 5, Iss 1, Pp 108-116 (2024)
Druh dokumentu: article
ISSN: 2096-8965
DOI: 10.12287/j.issn.2096-8965.20240113
Popis: Objective To investigate the neuroprotective effects and mechanisms of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Parkinson's Disease (PD) animal models. Methods SD rats were divided into five groups: sham-operated group (Sham group), PD group (Parkinson's modeling group), PD + PACAP_low concentration group (modeling + 5 μg / kg of PACAP intranasal administration according to body weight), PD+ PACAP_medium concentration group (modeling + 10 μg / kg of PACAP intranasal administration according to body weight), PD+ PACAP_high concentration group (modeling + 20 μg / kg of PACAP intranasal administration according to body weight). Each group included 10 animals. The four PD models were established by injecting lipopolysaccharide solution into the substantia nigra of SD rats. The Sham group was operated in the same way but injected with saline. The behavioral performance of the rats was assessed using the rotarod test. The concentration of glutamate (Glu) and the levels of α-synuclein (α-syn) in the substantia nigra were detected using ELISA. The expression levels of α-syn in the substantia nigra, as well as those of κ-light chain of nuclear factoractivated B-cells (NF- κB) and inhibitor of nuclear factor κB (IκBα) were detected using WB analysis. Quantitative Polymerase Chain Reaction (qPCR) was used to detect the mRNA expression levels of the rat nigral inflammatory factors Tumor Necrosis Factor α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6). WB and immunofluorescence methods were used to detect the levels of nuclear transcription factor Glial Fibrillary Acidic Protein (GFAP) to observe the activation level of astrocytes, and the TUNEL method was used to detect apoptosis in nigrostriatal neurons. Results (1) Behavioral results from the rotarod test indicated that compared to the Sham group, the PD group had a shorter latency and an increased number of falls (37.20±5.27 falls /min). In comparison to the PD group, the PACAP group showed a prolonged latency and a decreased number of falls (14.50±2.32 falls/min). As the concentration of PACAP increased, the latency in the PACAP group was prolonged, and the number of falls decreased (P
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