Association of CaMK2A and MeCP2 signaling pathways with cognitive ability in adolescents

Li Ching Lee, Ming Tsan Su, Hsing Ying Huang, Ying Chun Cho, Ting Kuang Yeh*, Chun Yen Chang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


The glutamatergic signaling pathway is involved in molecular learning and human cognitive ability. Specific single variants (SNVs, formerly single-nucleotide polymorphisms) in the genes encoding N-methyl-d-aspartate receptor subunits have been associated with neuropsychiatric disorders by altering glutamate transmission. However, these variants associated with cognition and mental activity have rarely been explored in healthy adolescents. In this study, we screened for SNVs in the glutamatergic signaling pathway to identify genetic variants associated with cognitive ability. We found that SNVs in the subunits of ionotropic glutamate receptors, including GRIA1, GRIN1, GRIN2B, GRIN2C, GRIN3A, GRIN3B, and calcium/calmodulin-dependent protein kinase IIα (CaMK2A) are associated with cognitive function. Plasma CaMK2A level was correlated positively with the cognitive ability of Taiwanese senior high school students. We demonstrated that elevating CaMK2A increased its autophosphorylation at T286 and increased the expression of its downstream targets, including GluA1 and phosphor- GluA1 in vivo. Additionally, methyl-CpG binding protein 2 (MeCP2), a downstream target of CaMK2A, was found to activate the expression of CaMK2A, suggesting that MeCP2 and CaMK2A can form a positive feedback loop. In summary, two members of the glutamatergic signaling pathway, CaMK2A and MeCP2, are implicated in the cognitive ability of adolescents; thus, altering the expression of CaMK2A may affect cognitive ability in youth.

Original languageEnglish
Article number152
JournalMolecular Brain
Issue number1
Publication statusPublished - 2021 Dec


  • Calcium/calmodulin-dependent protein kinase IIα (CaMK2A)
  • Cognitive function
  • Glutamatergic signaling pathway
  • Methyl-CpG binding protein 2 (MeCP2)
  • Single-nucleotide variant (SNV)

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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