Hippocampal insulin signaling and neuroprotection mediated by physical exercise in Alzheimer´s Disease

Abstract

-Epidemiological studies indicate continuous increases in the prevalence of Alzheimer's Disease (AD) in the next few decades. The key feature of this disease is hippocampal neurodegeneration. This structure has an important role in learning and memory. Intense research efforts have sought to elucidate neuroprotective mechanisms responsible for hippocampal integrity. Insulin signaling seems to be a very promising pathway for the prevention and treatment of AD. This hormone has been described as a powerful activator of neuronal survival. Recent research showed that reduced insulin sensitivity leads to low-grade inflammation, and both phenomena are closely related to AD genesis. Concomitantly, exercise has been shown to exert anti-inflammatory effects and to promote improvement in insulin signaling in the hippocampus, which supports neuronal survival and constitutes an interesting non-pharmacological alternative for the prevention and treatment of AD. This review examines recent advances in understanding the molecular mechanisms involved in hippocampal neuroprotection mediated by exercise.

The Effect of Intrahippocampal Insulin Infusion on Spatial Cognitive Function and Markers of Neuroinflammation in Diet-induced Obesity

“…Mechanisms may vary according to phenotype. Insulin's signaling pathway drives cellular responses (e.g., gene transcription), and protein translation and transport (43, 44). McNay et al (25) showed that intrahippocampal delivery of insulin, and not IGF-1, enhanced spatial working memory via PI3K pathways, and that blockage of endogenous hippocampal insulin impaired cognitive performance.…”

Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration

“…Among these regions, the hippocampus plays an important role in storing new memories [ 77 ]. During normal physiological conditions, insulin and growth factors like BDNF, insulin like growth factors 1 and 2 (IGF-1 and 2) and VEGF transmit intracellular signals in the hippocampal neurons for their integrity and to keep hippocampus functional [ 78 ]. However, when the functionality of these growth factors is inhibited, the possibility of AD becomes high [ 78 ].…”

“…However, forced exercise(running daily for 20 min for two weeks)reversed this effect in 20 month-old rats [ 79 ]. PE has been shown to exert anti-inflammatory effects and enhances insulin signaling in the hippocampal neurons [ 78 ]. PE also elicits an insulin sensitizing effect in the peripheral nervous system [ 80 ] and hence the possibility of it to bring about the same effect in the central nervous system and play a neuroprotective role is quite possible [ 81 ].…”

The Potential Role of Exercise-Induced Neurotrophic Factors for Mental Health

“…However, recent evidence has shown that it also affects nerve cells and plays an important role in hippocampal neurogenesis and neuroprotection [113]. As BDNF or IGF-1, exercise-induced VEGF may have a role in ameliorating the pathological process of AD [114]. Moreover, VEGF, because of its active role in neurogenesis, may mediate antidepressant therapies [115].…”