Recent studies have shown that daily walking is beneficial to prevent cognitive decline during aging. However, the basic mechanisms of how walking prevents dementia are still unknown. Therefore, the purpose of our study was to clarify neural mechanisms related to that question.
The cerebral cortex and hippocampus typically demonstrate decreases in blood flow in the course of aging and Alzheimer's type-dementia. These structures receive cholinergic fibers from basal forebrain nuclei. Our animal experiments revealed that stimulation of the cholinergic nuclei enhanced acetylcholine release and dilated intracerebral artery resulting in increased blood flow to the cerebral cortex and hippocampus, enhanced secretion of nerve growth factor and reduced ischemia-induced neuronal damage 1,2. Therefore, activation of the cholinergic system appears to be beneficial for brain health.
We then hypothesized that walking activated the cholinergic system and increased blood flow. To examine this hypothesis, we made rats walk on a treadmill while measuring hippocampal blood flow and blood pressure. We found that walking at a slow or normal pace resulted in acetylcholine release and increased hippocampal blood flow in both young and aged rats, with only small increases in blood pressure 1,3. To eliminate emotional influence, we performed experiments under anesthesia and showed that skin brushing4, acupuncture-like stimulation5, and joint movement also produced similar effects as walking.
In Alzheimer's-type dementia, the number of cholinergic neurons are greatly reduced. Therefore, drugs for dementia are usually aimed at increasing the remaining acetylcholine by preventing degradation and loss. However, in the normal elderly, the majority of cholinergic neurons are maintained. Therefore, we may be able to prevent cholinergic neuron loss and resulting dementia by activating cholinergic systems through daily walking or somatosensory stimulation.
1. Hotta H, Uchida S: Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation. Geriatr Gerontol Int, 10 Suppl 1: S127-136, 2010.
2. Hotta H, Masamoto K, Uchida S, Sekiguchi Y, Takuwa H, Kawaguchi H, Shigemoto K, Sudo R, Tanishita K, Ito H, Kanno I: Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex. J Cereb Blood Flow Metab, 33: 1440-1447, 2013.
3. Nakajima K, Uchida S, Suzuki A, Hotta H, Aikawa Y: The effect of walking on regional blood flow and acetylcholine in the hippocampus in conscious rats. Auton Neurosci, 103: 83-92, 2003.
4. Piché M, Uchida S, Hara S, Aikawa Y, Hotta H: Modulation of somatosensory-evoked cortical blood flow changes by GABAergic inhibition of the nucleus basalis of Meynert in urethane-anaesthetized rats. J Physiol, 588: 2163-2171, 2010.
5. Uchida S, Kagitani F: Effect of acupuncture-like stimulation on cortical cerebral blood flow in aged rats. J Physiol Sci, 65: 67-75, 2015.