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

Abstract

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 β-adrenergic receptor function, and decreased α-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.

Keywords:

• Cognitive function
• Diet restriction
• High affinity choline transport
• Muscarinic receptors
• Tyrosine