Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

• Published in: Biomedicine & pharmacotherapy 2019-02, Vol.110, p.168-180
• Main Authors: Wong, Jia Hui, Muthuraju, Sangu, Reza, Faruque, Senik, Mohd Harizal, Zhang, Jingli, Mohd Yusuf Yeo, Nor Aqilah Binti, Chuang, Huei Gau, Jaafar, Hasnan, Yusof, Siti Rafidah, Mohamad, Habsah, Tengku Muhammad, Tengku Sifzizul, Ismail, Nor Hadiani, Husin, Siti Sarwana, Abdullah, Jafri Malin
• Format: Article
• Language: English
• Subjects: AMPAR; Centella asiatica; Learning and memory; NMDAR
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.11.044

•Centella asiatica (CA) extract enhances learning and memory.•CA extract increases expression of AMPAR subunits GluA1 and GluA2.•CA extract increases expression of NMDAR subunit GluN2B while reduces GluN2A.•CA extract did not cause neuronal damage. Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was signif