Forced exercise: A lifestyle strategy to mitigate bradykinesia by increasing dopamine signaling and glutamate uptake in nigrostriatal neurons of aged rats
Monday, Nov 11, 2013, 9:00 AM -10:00 AM
++C.06.b. Physiological and molecular correlates
*J. C. ARNOLD
, V. FIELDS
, D. K. INGRAM
, M. F. SALVATORE
Pharmacology, Toxicology, & Neurosci., Louisiana State Univ. Hlth. Sci. Ctr., Shreveport, LA;
Nutritional Neurosci. and Aging Lab., Pennington Biomed. Res. Ctr., Baton Rouge, LA
Bradykinesia will affect ~50% of the elderly population by age 85, impairing their ability to execute locomotor function and increasing the risk of injury and mortality. Nigrostriatal dopamine (DA) neurons are vital for executing voluntary movement, and aging may challenge their function in two major ways; impaired DA biosynthesis in their cell bodies, and impaired glutamate uptake at their terminals. In Parkinson’s disease (PD), bradykinesia emerges when striatal DA loss exceeds 70%, but this level of loss has never been observed in aging. However, similar levels of DA loss in the substantia nigra are detected with bradykinesia in PD and aging. Furthermore, nigral DA is significantly correlated to locomotor activity, and may be a target to improve bradykinesia. The loss of nigrostriatal DA neurons in PD impairs not only dopaminergic, but also glutamatergic neurotransmission, resulting in increased extracellular glutamate in PD models. Glutamate transporters remove extracellular glutamate, reducing the constant potential for glutamate excitotoxicity. In aging, however, striatal glutamate uptake and glutamate transporter expression is diminished, conceivably resulting in increased extracellular glutamate, and potentially creating an excitotoxic environment to nigrostriatal DA neurons. Given the similarities of these molecular deficiencies in both PD and aging models, we hypothesize that forced exercise (EX), a strategy shown to mitigate bradykinesia in PD models and patients, may similarly improve locomotor function in aged rats in association with increased DA biosynthesis and glutamate uptake capacity. Our preliminary work demonstrates that 12 consecutive days of treadmill EX may prevent aging-related bradykinesia, as exhibited in non-exercised counterparts. Additionally, we have evidence to show that EX increases striatal glutamate uptake in aged rats. We speculate that EX-mediated prevention of bradykinesia is associated with increased nigral DA tissue content, via increased expression of tyrosine hydroxylase. Results from these studies may delineate molecular targets to prevent bradykinesia in aging while providing a non-pharmacological, clinically translatable strategy to improve locomotion in elderly individuals with locomotor impairments.
NIH Grant AG040261
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