EFFECTS OF METABOLIC ACIDOSIS ON MOTOR AND COGNITIVE FUNCTION IN YOUNG AND AGED MICE

Purpose: Metabolic acidosis is defined as a reduction of serum pH below 7.4 due to the inability of the kidneys to remove an adequate proportion of hydrogen protons (H+), and can be a symptom of diabetes, kidney disease, and aging. The effects of acidosis on the nervous system are not well understood, and little research has been done to establish those effects and their potential role in cognitive decline. Methods: Four- and twenty-month-old male C57BL/6J mice (n=8) were fed either a control diet or the control diet supplemented with 2% ammonium chloride (NH4Cl) to induce metabolic acidosis. Urine pH was measured weekly to insure inducement of acidosis in the NH4Cl supplemented diet groups. After 4 weeks of pre-treatment, the mice were tested for various functional tasks and remained on their respective diet during behavioral testing. The tests were done in the following order: locomotor activity, reflexes, wire suspension, bridge walking, active avoidance (T-maze), and Morris water maze. Results: Overall, urine pH of the mice on the NH4Cl diet was decreased compared to control mice. Though the NH4Cl diet did not seem to affect the weights of the young mice, a significant decrease was seen in the aged mice. Aged mice on the NH4Cl diet had increased spontaneous activity and better performance on motor tasks. On spatial learning and memory, the NH4Cl mice learned to locate the platform more efficiently than their age-matched controls. In general, the NH4Cl mice took fewer trials to reach the criteria of avoidance and discrimination. Conclusions: Interestingly, the data suggest a potential benefit on motor and cognitive function of a mild acidosis in young and aged mice. More studies will solidify these observed effects and identify a potential mechanism by investigating acid sensing ion channel concentration in various brain regions through immunoblot analysis.