Neonatal immune challenge exacerbates seizure-induced hippocampus-dependent memory impairment in adult rats.
Our aim was to examine whether neonatal lipopolysaccharide (LPS) exposure is associated with changes in microglia and whether these alternations could influence later seizure-induced neurobehavioral outcomes. Male pups were first injected intraperitoneally with either LPS or saline on postnatal day 3 (P3) and postnatal day 5 (P5). Immunohistochemical analysis showed that LPS-treated animals exhibited increased microglia activation that persisted into adolescence. At P45, seizures were induced in rats by intraperitoneal injection of kainic acid (KA). Rats treated with LPS neonatally showed significantly greater proinflammatory responses and performed significantly worse in the Y-maze, Morris water maze, and inhibitory avoidance tasks after KA insult. Treatment with minocycline at the time of neonatal LPS exposure to block LPS-induced microglia alternation attenuated the exaggerated neuroinflammatory responses and alleviated memory impairment associated with the KA insult. Our findings suggest that neonatal immune activation can predispose the brain to exacerbated behavioral deficits following seizures in adulthood, possibly by priming microglia.
Pediatric Department of Qilu Hospital, Shandong University, Jinan, China.
Ping
P
Yin
Zhen
Z
Li
Ying-Yan
YY
Wang
Na-Na
NN
Qiao
Shan-Ying
SY
Huang
Ruo-Peng
RP
Sun
Ji-Wen
JW
Wang
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D008911:Minocycline / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications* / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D008911:Minocycline; D007608:Kainic Acid