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Int Neurourol J. 2018 Oct;22(Suppl 3):S156-164. doi: 10.5213/inj.1836224.112. Epub 2018 Oct 31.

PI3K-Akt-Wnt Pathway Is Implicated in Exercise-Induced Improvement of Short-term Memory in Cerebral Palsy Rats.

Author information

1
Department of Physical Therapy, Kyung Hee University Medical Center, College of Medicine, Kyung Hee University, Seoul, Korea.
2
Department of Physical Therapy, Hosan University, Gyeongsan, Korea.
3
Department of Sports Healthcare, College of Humanities & Social Sciences, Inje University, Gimhae, Korea.
4
Department of Golf Mapping, College of Arts Physical Education, Joongbu University, Geumsan, Korea.
5
Division of Leisure & Sports Science, Department of Exercise Prescription, Dongseo University, Busan, Korea.
6
Department of Internal Medicine, Kyung Hee University Hospital at Gandong, College of Medicine, Kyung Hee University, Seoul, Korea.
7
Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, Seoul, Korea.

Abstract

PURPOSE:

Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively.

METHODS:

Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks.

RESULTS:

Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups.

CONCLUSION:

The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway.

KEYWORDS:

Cerebral palsy; Glycogen synthase kinase-3β; Phosphatidylinositol 3-kinase; Protein kinase B; Short-term memory

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