Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930.
Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurological cognitive deficits. In rats at postnatal days 10-12 (P10-P12), global hypoxia induced spontaneous seizures and chronic brain injury, mimicking clinical aspects of neonatal hypoxia. Synaptic Ras-GTPase activating protein (SynGAP) has important roles in RAS/MAPK-dependent synaptic plasticity and mammalian learning. We investigated possible alterations of SynGAP expression occurring in memory-impaired animals previously exposed to perinatal hypoxia insults. We also evaluated the therapeutic efficacy of A68930, a selective agonist of dopamine D1/D5 receptors, on perinatal hypoxia insults. In the hippocampal CA1 region, perinatal hypoxia insults (P10) led to a reduction in SynGAP expression associated with impairment in long-term spatial learning and memory performance at P45. The use of A68930 (at a dose of 1, 2, 3mg/kg, P17-P23) effectively attenuated the deleterious effects as described above. Our results may indicate the involvement of SynGAP in certain forms of brain injury, leading to long-term learning and memory deficits. A68930 may have clinical potential as a therapeutic agent for alleviation of long-term cognitive deficits in rats and other animal models.
Yang
San-Nan
SN
Graduate Institute of Clinical Medicine, Chang Gung University, Taiwan, ROC.
Huang
Chung-Bin
CB
Yang
Chin-Hwa
CH
Lai
Ming-Chi
MC
Chen
Wu-Fu
WF
Wang
Chih-Lu
CL
Wu
Chia-Lu
CL
Huang
Li-Tung
LT
D000818:Animals; D001238:Asphyxia Neonatorum / Q000188:drug therapy / Q000503:physiopathology; D002839:Chromans / Q000494:pharmacology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000503:physiopathology*; D007231:Infant, Newborn; D018782:Maze Learning; D008568:Memory / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000502:physiology
D002839:Chromans; D018491:Dopamine Agonists; D020690:GTPase-Activating Proteins; C112202:Syngap1 protein, rat; C065380:A 68930