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. 2014 Apr 30;10(2):81-8.
doi: 10.12965/jer.140102. eCollection 2014 Apr.

Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer's disease rats

Young-Je Sim  1
Affiliations

Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer's disease rats

Young-Je Sim. J Exerc Rehabil. .

Abstract

Alzheimer's disease is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. Exercise increases cognitive ability, attenuates motor deficits, increases new neuron formation, and ameliorates neurological impairments in several neurodegenerative diseases. This study investigated the effects of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus. The rat model of Alzheimer's disease was induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise groups were forced to run on a treadmill for once 30 min daily for 28 consecutive days starting at 3 days after the ICV injection of STZ. Radial 8-arm maze test was conducted for the spatial learning ability. New neuron formation in the hippocampus was detected by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. The present results show that ICV injection of STZ impaired spatial learning ability. Decreased cell proliferation with decrement of BDNF and TrkB expressions in the hippocampus were observed in the STZ-induced Alzheimer's disease rats. However, treadmill exercise alleviated deficits of spatial learning ability. Treadmill exercise enhanced cell proliferation and increased BDNF and TrkB expressions in the rats with ICV injection of STZ. The present study suggests that treadmill exercise can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.

Keywords: Alzheimer’s disease; Brain-derived neurotrophic factor; Cell proliferation; Spatial learning ability; Treadmill exercise.

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Figures

Fig. 1.
Fig. 1.
Effect of treadmill exercise on spatial learning memory in the radial 8-arm maze test. Upper: Time to complete performance. Middle: Number of correct choice. Lower: Number of error choice. Sham: Sham-operation group, Sham-EX: sham-operation and treadmill exercise group, AD: AD-induced group, AD-EX: AD-induced and treadmill exercise group. *Represents P< 0.05 compared to the sham-operation group. #Represents P< 0.05 compared to the AD-induced group. n.s: non significantly.
Fig. 2.
Fig. 2.
Effect of treadmill exercise on cell proliferation in the hippocampal dentate gyrus. Upper: Phtomicrographs of 5-bromo-2’-deoxyuridine (BrdU) positive cells in the dentate gyrus. The scale bar represents 250 μm. Lower: Number of BrdU-positive cells in each group. Sham: Sham-operation group, Sham-EX: sham-operation and treadmill exercise group, AD: AD-induced group, AD-EX: AD-induced and treadmill exercise group. *Represents P< 0.05 compared to the sham-operation group. #Represents P< 0.05 compared to the AD-induced group.
Fig. 3.
Fig. 3.
Effect of treadmill exercise on BDNF and TrkB expressions in the hippocampus. Left: BDNF expression in the hippocampus. Right: TrkB expression in the hippocampus. Sham: Sham-operation group, Sham-EX: sham-operation and treadmill exercise group, AD: AD-induced group, AD-EX: AD-induced and treadmill exercise group. *Represents P< 0.05 compared to the sham-operation group. #Represents P< 0.05 compared to the AD-induced group.
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References

    1. Agrawal R, Tyagi E, Shukla R, Nath C. Insulin receptor signaling in rat hippocampus: A study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol. 2011;21:261–273. - PubMed
    1. Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T. A natural scaven¬ger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25–35. Behav Brain Res. 2007;180:139–145. - PubMed
    1. Arabpoor Z, Hamidi G, Rashidi B, Shabrang M, Alaei H, Sharifi MR, Salami M, Dolatabadi HR, Reisi P. Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer’s disease. Adv Biomed Res. 2012;1:50–55. - PMC - PubMed
    1. Archer T. Physical exercise alleviates debilities of normal aging and Alzheimer’s disease. Acta Neurol Scand. 2011;123:221–238. - PubMed
    1. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389–404. - PMC - PubMed