Research Article: Inhibition of PI3K-Akt Signaling Blocks Exercise-Mediated Enhancement of Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus

Date Published: November 19, 2009

Publisher: Public Library of Science

Author(s): Elodie Bruel-Jungerman, Alexandra Veyrac, Franck Dufour, Jennifer Horwood, Serge Laroche, Sabrina Davis, Olivier Jacques Manzoni. http://doi.org/10.1371/journal.pone.0007901

Abstract: Physical exercise has been shown to increase adult neurogenesis in the dentate gyrus and enhances synaptic plasticity. The antiapoptotic kinase, Akt has also been shown to be phosphorylated following voluntary exercise; however, it remains unknown whether the PI3K-Akt signaling pathway is involved in exercise-induced neurogenesis and the associated facilitation of synaptic plasticity in the dentate gyrus.

Partial Text: It is well accepted that cell proliferation and neurogenesis continue to occur in selected brain regions of the adult brain, notably the subgranular zone of the dentate gyrus (DG) and the subventricular zone of the lateral ventricles [1]. Different forms of physiological and pathological conditions can promote neurogenesis, such as exercise [2] and environmental enrichment [3]–[5] and injurious circumstances such as ischaemia or seizures [1].

During the 10 days of exercise, as we controlled the amount of running, DMSO and LY294002 treated rats from the three different experiments were pooled for analyses. All animals ran an almost identical number of kilometers per day with no difference between rats treated with DMSO (n = 18) and those treated with LY294002 (n = 19) across days (F(1,35) = 0.175; p = 0.678; Fig. 1B) or in terms of total km run (F(1,35) = 0.277; p = 0.603); both groups, however showing a comparable and significant increase in running over the 10 days (F(1,9) = 28.8; p = 0.0001).

Currently there is a great deal of effort being made to understand the potential cell-signaling mechanisms that drive experience-dependent neurogenesis in the adult brain. Certain regulators of proliferation and survival of newborn cells have been identified, that include growth factors and morphogens, hormones, certain neurotransmitters, intracellular signaling molecules and transcription factors [1]. Much of this knowledge however derives from studies in cell cultures, while the mechanisms associated with neurogenesis in the intact, behaving animal remain poorly defined. To date, it is clear that growth factors are necessary for neurogenesis in the behaving animal [30]–[31], and some studies have shown that genetic or pharmacological inactivation of growth-related molecules, such as VEGF, SDF-1, FGF-2, and IGF-1 implicated in neurogenesis can abrogate the beneficial effect of exercise or environmental enrichment on neurogenesis and on learning and memory or synaptic plasticity [1], [32]–[34].

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http://doi.org/10.1371/journal.pone.0007901

 

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