Diet restriction in mice causes a decrease in hippocampal choline uptake and muscarinic receptors that is restored by administration of tyrosine: interaction between cholinergic and adrenergic receptors influencing cognitive function.
We have studied the effects of diet restriction (DR) to 60% and 40% of daily requirements, and tyrosine administration on cognitive function in mice, to define the nutritional-neurochemical interactions on autonomic tone involved in behavior and energy regulation. Cognitive function in the Morris Water maze was significantly impaired after 40% DR compared to both control and 60% DR. It was restored after tyrosine in association with increased M1 cholinergic and beta-adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40% significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or acetyl cholinesterase (AChE) activity. Tyrosine administration significantly increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01) without changes in affinity. ChAT activity was decreased after tyrosine--significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and protein were not influenced by DR or tyrosine administration. Tyrosine hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of cholinergic activity by adrenergic tone. Nutritional effect on behavior and autonomic tone may have implications for the treatment of mood changes associated with weight loss and semi-starvation.
Avraham
Y
Y
Department of Human Nutrition and Metabolism, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Hao
S
S
Mendelson
S
S
Bonne
O
O
Berry
E M
EM
D000818:Animals; D001692:Biological Transport; D002794:Choline / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004038:Diet, Reducing; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D043643:Receptor, Muscarinic M1; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000494:pharmacology / Q000627:therapeutic use*
C086088:CHRM1 protein, human; D043643:Receptor, Muscarinic M1; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D014443:Tyrosine; D002794:Choline