title: TNP-ATP is Beneficial for Treatment of Neonatal Hypoxia-Induced Hypomyelination and Cognitive Decline.
abstract: Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 (P0) rat pups to systemic hypoxia (3.5 h). We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP analogue 2',3'-0-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 receptors), whereas treatment with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; inhibits P2X1-3 and P2X5-7 receptors) was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia.
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Longjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Lixuan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China. leefan623@sina.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D015151:Immunoblotting; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009186:Myelin Sheath / Q000473:pathology*; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate
keywords: Glutamate; Inflammation; Ionotropic ATP receptors; Memory deficit; Neonatal hypoxia