Korean J Physiol Pharmacol.  2012 Oct;16(5):305-312. 10.4196/kjpp.2012.16.5.305.

Effects of Treadmill Exercise on the Recovery of Dopaminergic Neuron Loss and Muscle Atrophy in the 6-OHDA Lesioned Parkinson's Disease Rat Model

• Choe MA
• Koo BS
• An GJ
• Jeon S

• KMID: 1493962
• DOI: http://doi.org/10.4196/kjpp.2012.16.5.305

Abstract

This study was to determine the effect of exercise on the recovery of dopaminergic neuron loss and muscle atrophy in 6-OHDA-induced hemi Parkinson's disease model. Exercise was loaded twice per day for 30 minutes each time, at 5 days after 6-OHDA lesioning and continued for 16 days using a treadmill. Exercise significantly increased the number of tyrosine hydroxylase positive neuron in the lesioned substantia nigra and the expression level of tyrosine hydroxylase in the striatum compared with the control group. To examine which signaling pathways may be involved in the exercise, the phosphorylation of GSK3beta and ERK were observed in the striatum. In the control group, basal level of GSK3beta phosphorylation was less than in both striatum, but exercise increased it. ERK phosphorylation decreased in the lesioned striatum, but exercise recovered it. These findings suggest that exercise inactivates GSK3beta by phosphorylation which may be involved in the neuroprotective effect of exercise on the 6-OHDA-induced cell death. In the exercise group, weight, and Type I and II fiber cross-sectional area of the contralateral soleus significantly recovered and expression of myosin heavy chain and Akt and ERK phosphorylation significantly increased by exercise. These results suggest that exercise recovers Parkinson's disease induced dopaminergic neuron loss and contralateral soleus muscle atrophy.

Keyword

ERK; Exercise; GSK3beta; Muscle atrophy; Parkinson's disease

MeSH Terms

Animals
Atrophy
Cell Death
Dopaminergic Neurons
Glycogen Synthase Kinase 3
Muscle, Skeletal
Muscles
Muscular Atrophy
Myosin Heavy Chains
Neurons
Neuroprotective Agents
Oxidopamine
Parkinson Disease
Phosphorylation
Rats
Substantia Nigra
Tyrosine 3-Monooxygenase
Glycogen Synthase Kinase 3
Myosin Heavy Chains
Neuroprotective Agents
Oxidopamine
Tyrosine 3-Monooxygenase

Figure

• 

  Fig. 1 Cross-sections of the hindlimb muscles in control (left) and exercise (right) rats. The first line is left (ipsilateral) soleus in control and exercise rats. The second line is left plantaris in control and exercise rats. The third line is right (contralateral) soleus in control and exercise rats. The fourth line is right plantaris in exercise and control rats. Dark=Type I muscle fiber, light=Type II muscle fiber (Myosin ATPase straining, 100×).

• 

  Fig. 2 TH-specific immunohistochemical staining and the number of TH positive neurons in substantia nigra of unilateral 6-OHDA lesioned Parkinson rat. The data represent the means±SEM. *Significant difference between left and right SN in the control group and control and exercise group of 6-OHDA lesioned side (p<.01).

• 

  Fig. 3 TH-immunoblot in the striatum of unilateral 6-OHDA lesioned Parkinson rat. The striatum was lysed and inmmunoblotted with anti-TH antibody. The intensity of the TH bands was quantitated by densitometry and it was normalized versus the actin. The data are expressed as mean±SEM with 9 rats per group. *Significant difference between control and exercise group of 6-OHDA lesioned side (p<.01).

• 

  Fig. 4 ERK and GSK3β phosphorylation in the striatum of unilateral 6-OHDA lesioned Parkinson rat. The striatum was lysed and inmmunoblotted with pGSK3β or GSK3β (A), anti-pERK, ERK (B) antibody. The intensity of the protein bands was quantitated by densitometry and the phosphorylated form was normalized versus the total form. The data are expressed as mean±SEM with 9 rats per group. *Significant difference between left and right SN in the control group and control and exercise group of each side (p<.01).

• 

  Fig. 5 ERK and Akt phosphorylation in the soleus muscle of unilateral 6-OHDA lesioned Parkinson rat. (A) The soleus was lysed and inmmunoblotted with each antibody. The intensity of the protein bands was quantitated by densitometry and the phosphorylated form was normalized versus the total form. (B) The soleus was lysed and inmmunoblotted with anti-MHC antibody. The intensity of the protein bands was quantitated by densitometry and it was normalized versus the actin. The data are expressed as mean±SEM with 9 rats per group. †Significant difference between left and right soleus in the control group, *Significant difference between control and exercise group of each side (p<.01).

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