Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion

Brain Res. 2002 Nov 1;954(1):32-41. doi: 10.1016/s0006-8993(02)03300-0.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism
  • Carotid Artery, Common / surgery
  • Cerebral Cortex / blood supply
  • Cerebrovascular Circulation / drug effects*
  • Cerebrovascular Disorders
  • Dietary Fats, Unsaturated / administration & dosage*
  • Fatty Acids, Essential / administration & dosage*
  • Hippocampus / metabolism
  • Male
  • Perfusion
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1

Substances

  • Dietary Fats, Unsaturated
  • Fatty Acids, Essential
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1