Treadmill exercise modifies dopamine receptor expression in the prefrontal cortex of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson’s disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder for which there is no cure. PD is a dopamine (DA)-deficit disorder marked by progressive motor and nonmotor disturbances, including cognitive impairment. Executive function (EF) is the most common subtype of cognitive impairment in PD and consists of deficits in number of processes including behavioral flexibility. The prefrontal cortex (PFC) is an important brain region subserving EF. Furthermore, DA plays a key neuromodulatory role in the PFC and altered DA neurotransmission is believed to contribute toward EF deficits in PD. The mechanisms underlying PFC dysfunction are not fully understood and there are no effective treatments for EF deficits in PD. Exercise is a promising therapeutic strategy that may exert beneficial effects on PFC function in PD. Our previous work suggests that exercise improves motor function and restores striatal DA-D2 receptor (DA-D2R) expression after DA depletion. This study builds upon our previous work by exploring whether exercise modulates PFC function, specifically DA levels and DA receptor expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mouse model of DA depletion. We found that exercise restores PFC DA levels, reverses the MPTP-induced increase in DA-D1R and decrease in DA-D4R, and exerts differential effects on D2Rs. The modest effect of exercise in PFC function may suggest that other types of exercise, such as those that are more skill based, would be required to target these cognitive behavioral circuits.

Exercise induces region‐specific remodeling of astrocyte morphology and reactive astrocyte gene expression patterns in male mice

“…from midline to the corpus callosum, and −1.5 to −3.0 mm D.V.) (Kintz, Petzinger, & Jakowec, ); (ii) STR (Bregma +1.2 to −0.2 mm A.P., including tissue bordered ventrally by the anterior commissure, dorsally by the corpus callosum, medially by the lateral ventricle, and ±2.5 mm laterally from the midline) (Kintz et al, ); and (iii) ETC (Bregma −2.0 to −3.0 mm A.P., laterally bounded by the edge of the cortex and extending 1 mm medially to the edge of the striatum, and −3.0 to −3.5 mm D.V.) Tissues were placed in RNA later Stabilization Solution (QIAGEN, Germantown, MD) and stored at 4°C overnight.…”

Parkinson’s Disease and the COVID-19 Pandemic

“…Whether chronic stress can truly permanently worsen PD, however, remains unknown. On the other hand, aerobic exercise protects against progression of parkinsonian symptoms [ 44 ] and may even enhance neuroplasticity and dopamine receptor expression in PD [ 45, 46 ]. Subjective worsening of anxiety and cognitive symptoms was demonstrated among 28 PD patients along with a mean mini-mental state examination score drop of 0.5 points before vs. during lockdown [ 47 ].…”

“…Whether chronic stress can truly permanently worsen PD, however, remains unknown. On the other hand, aerobic exercise protects against progression of parkinsonian symptoms [44] and may even enhance neuroplasticity and dopamine receptor expression in PD [45,46].…”

A Parkinson’s disease patient displaying increased neuromelanin-sensitive areas in the substantia nigra after rehabilitation with tDCS: a case report

“…Physical rehabilitation may also have beneficial effects on dopaminergic neurons. Previous studies with a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) demonstrated that treadmill exercise could modify dopamine receptor expression in the PFC (Kintz et al, 2017;Petzinger et al, 2007), improve motor performance, and restore striatal dopaminergic receptors (Vučković et al, 2010). Other mouse model studies demonstrated that treadmill exercise restored dendritic spine loss in medium spiny neurons in the striatum (Toy et al, 2014;Vučković et al, 2010).…”