Effects of postnatal dietary choline manipulation against MK-801 neurotoxicity in pre- and postadolescent rats.
Prenatal supplementation of rat dams with dietary choline has been shown to provide their offspring with neuroprotection against N-methyl-d-aspartate (NMDA) antagonist-mediated neurotoxicity. This study investigated whether postnatal dietary choline supplementation exposure for 30 and 60 days of rats starting in a pre-puberty age would also induce neuroprotection (without prenatal exposure). Male and female Sprague-Dawley rats (postnatal day 30 of age) were reared for 30 or 60 concurrent days on one of the four dietary levels of choline: 1) fully deficient choline, 2) 1/3 the normal level, 3) the normal level, or 4) seven times the normal level. After diet treatment, the rats received one injection of MK-801 (dizocilpine 3mg/kg) or saline control. Seventy-two hours later, the rats were anesthetized and transcardially perfused. Their brains were then postfixed for histology with Fluorojade-C (FJ-C) staining. Serial coronal sections were prepared from a rostrocaudal direction from 1.80 to 4.2mm posterior to the bregma to examine cell degeneration in the retrosplenial and piriform regions. MK-801, but not control saline, produced significant numbers of FJ-C positive neurons, indicating considerable neuronal degeneration. Dietary choline supplementation or deprivation in young animals reared for 30-60days did not alter NMDA antagonist-induced neurodegeneration in the retrosplenial region. An interesting finding is the absence of the piriform cortex involvement in young male rats and the complete absence of neurotoxicity in both hippocampus regions and DG. However, neurotoxicity in the piriform cortex of immature females treated for 60days appeared to be suppressed by low levels of dietary choline.
Biasi
Elisabetta
E
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Elisabetta.biasi@libero.it
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements / Q000592:standards; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D009498:Neurotoxins; D016291:Dizocilpine Maleate; D002794:Choline