Biomolecules & Therapeutics

  • 제30권4호
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  • Pages.320-327
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  • 2022
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development

  • Adil, Keremkleroo Jym (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Remonde, Chilly Gay (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Gonzales, Edson Luck (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Boo, Kyung-Jun (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Kwon, Kyong Ja (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Kim, Dong Hyun (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Cheong, Jae Hoon (School of Pharmacy, Jeonbuk National University) ;
  • Shin, Chan Young (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Jeon, Se Jin (Department of Pharmacology, School of Medicine, Konkuk University)
  • 투고 : 2021.12.26
  • 심사 : 2022.01.11
  • 발행 : 2022.07.01
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초록

Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

키워드

과제정보

This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean Government (MSIT) (NRF-2017M3A9G2077568) and the NRF (2016R1A5A2012284).

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