Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats.
Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane fraction of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.
Högyes
E
E
Department of Animal Physiology, University of Groningen, Kerklaan 30, POB 14, 9750 AA, Haren, The Netherlands.
Nyakas
C
C
Kiliaan
A
A
Farkas
T
T
Penke
B
B
Luiten
P G M
PG
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D005526:Food, Formulated; D008563:Membrane Lipids / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D016896:Treatment Outcome
D008563:Membrane Lipids; D018696:Neuroprotective Agents; D009498:Neurotoxins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D004281:Docosahexaenoic Acids; D016202:N-Methylaspartate; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase