Differential aging-related changes of D1, D2, and D3 dopamine receptor expression in the striatum

Abstract

Aging is associated with a decrease in motor function and a concomitant increase in muscle stiffness and tone. The striatum plays a critical role in the control of motor function, and it receives strong dopamine (DA) innervation from the substantia nigra. DA actions are mediated by both excitatory D1-like (D1 and D5) and inhibitory D2-like (D2, D3, and D4) receptors, and D1, D2, and D3 receptor subtypes are thought to be involved in motor control, however there is a lack of data on aging-related DA receptor expression levels in the striatum. We hypothesize that the observed behavioral aging-related changes in motor control might be associated with a change in striatal DA receptor with age, possibly via a shift in inhibitory/excitatory DA receptor expression. Three groups of mice (C57BL/6) aged 2 months (n=4), 1 year (n=4), and 2 years (n=4) were used in this study. Striatal tissue was removed from the left hemisphere and Western blots were performed, to detect DA receptors D1, D2, and D3 expression levels (Abcam, D1: ab78021; D2: ab21218, D3: ab42114). DA receptor expression levels were normalized to ß-actin and the respective DA receptor expression in 2-month old animals. We found that with age, D1 receptor expression increased continuously and significantly over a ~4 fold increase (383.2 ±62.4 %) in the 1 year old and reached a ~5 fold increase (474± 49.5 %) in the 2 year old animals (p<0.001). In contrast, D2 receptor expression did not change with age (1 year: 110.8 ±2.81 %; 2 year: 121.0 ± 17.0 %, p = 0.556). Similarly, D3 receptor expression showed no change with age (1 4 year: 147.1 ± 6.83 %; 2 year: 122.1 ± 11.4 %, p = 0.078). Together these data indicate an increase in excitatory striatal DA receptor expression levels with age. Our data suggest that this net excitatory increase may play a role in the decline in motor function with age. It is tempting to speculate that the increase in D1 receptor expression might be a homeostatic compensation for the well-established reduction of DA levels with age.