title: Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats.
abstract: Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.
authors.affiliation: Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University, Seoul 143-701.
authors.forename: Edson Luck T
authors.initials: EL
authors.lastname: Gonzales
authors.affiliation: Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University, Seoul 143-701.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University, Seoul 143-701.
authors.forename: Chang Soon
authors.initials: CS
authors.lastname: Choi
authors.affiliation: Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University, Seoul 143-701.
authors.forename: Darine Froy N
authors.initials: DF
authors.lastname: Mabunga
authors.affiliation: Department of Pharmacy, Sahmyook University, Seoul 139-742.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Sahmyook University, Seoul 139-742.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 130-701.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Repulic of Korea.
authors.forename: Bon-Nyeo
authors.initials: BN
authors.lastname: Koo
authors.affiliation: Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University, Seoul 143-701 ; Department of Pharmacology, School of Medicine, Konkuk University, Seoul 143-701.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
keywords: Anesthesia; Learning and memory; Neurodevelopment; Propofol; Sex-difference; Weight gain