title: Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion.
abstract: The chronic dietary intake of essential polyunsaturated fatty acids (PUFAs) can modulate learning and memory by being incorporated into neuronal plasma membranes. Representatives of two PUFA families, the n-3 and n-6 types become integrated into membrane phospholipids, where the actual (n-6)/(n-3) ratio can determine membrane fluidity and thus the function of membrane-bound proteins. In the present experiment we studied hippocampal neurotransmitter receptors after chronic administration of n-3 PUFA enriched diets in a brain hypoperfusion model, which mimics decreased cerebral perfusion as it occurs in ageing and dementia. Male Wistar rats received experimental diets with a decreased (n-6)/(n-3) ratio from weaning on. Chronic experimental cerebral hypoperfusion was imposed by a permanent, bilateral occlusion of the common carotid arteries (2VO) at the age of 4 months. The experiment was terminated when the rats were 7 months old. Three receptor types, the muscarinic 1, serotonergic 1A and the glutaminergic NMDA receptors were labeled in hippocampal slices by autoradiographic methods. Image analysis demonstrated that 2VO increased muscarinic 1 and NMDA receptor density, specifically in the dentate gyrus and the CA3 region, respectively. The increased ratio of n-3 fatty acids in combination with additional dietary supplements enhanced the density of the serotonergic 1A and muscarinic 1 receptors, while n-3 fatty acids alone increased binding only to the muscarinic 1 receptors. Since the examined receptor types reacted differently to the diets, we concluded that besides changes in membrane fluidity, the biochemical regulation of receptor sensitivity might also play a role in increasing hippocampal receptor density.
authors.affiliation: Group of Molecular Neurobiology, Department of Animal Physiology, University of Groningen, Groningen, The Netherlands. farkase@anat-fm.szote.u-szeged.hu
authors.forename: Eszter
authors.initials: E
authors.lastname: Farkas
authors.forename: Martijn C
authors.initials: MC
authors.lastname: de Wilde
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
authors.forename: John
authors.initials: J
authors.lastname: Meijer
authors.forename: Jan N
authors.initials: JN
authors.lastname: Keijser
authors.forename: Paul G M
authors.initials: PG
authors.lastname: Luiten
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D017536:Carotid Artery, Common / Q000601:surgery; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005228:Fatty Acids, Essential / Q000008:administration & dosage*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1
chemical_list: D004042:Dietary Fats, Unsaturated; D005228:Fatty Acids, Essential; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1