Study of the Differences and Mechanisms in Synaptic Plasticity by the Orexin Signalling Pathway in the Rat Models of Insomnia by Using"Raw and Cooked Jujube Kernel"Together and Removing the Formula of AMD
- VernacularTitle:安寐丹"生熟枣仁"同用及拆方调控Orexin信号通路改善失眠大鼠模型突触可塑性的差异及机制探究
- Author:
Bo XU
1
;
Kang SUN
1
;
Ping WANG
1
;
Guangjing XIE
1
;
Zijing YE
1
;
Qinghua QIN
1
;
Jing XIA
1
Author Information
- Publication Type:Journal Article
- Keywords: AMD; Insomnia; Learning memory; Synaptic plasticity; OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(12):3218-3233
- CountryChina
- Language:Chinese
- Abstract: Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.
