Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes

Abstract

Neurons suffer detrimental effects from β-amyloid toxicity in Alzheimer's disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons against the Aβ-induced cell toxicity so far. In the present study, we investigated whether irisin could protect neurons against Aβ- (25–35) induced cell damage and explored the possible underlying mechanisms. Primary cell cultures of astrocytes and neurons were established. Conditioned medium from astrocyte was collected for the treatment and biochemistry assay study. To explore the protein expression changes, Western blot and ELISA assays were used in these in vitro cell culture models. Exposure of hippocampal neurons to 10 μM Aβ (25–35) caused significant reduction on cell viability, and the toxic effect was not significantly reduced by the coadministration of irisin. However, pretreated astrocyte-conditioned medium with irisin for 12 hours notably protected the neurons from the toxicity of Aβ. Also, we found that irisin could attenuate the release of IL-6 and IL-1β from cultured astrocytes and decrease the expression level of COX-2 and phosphorylation of AKT. Last, we found that irisin could reduce NFκB activation in astrocyte exposed to Aβ by preventing the phosphorylation and the loss of IκBα. Our finding may provide novel evidence for the future application of irisin in the treatment of Alzheimer's disease and the memory dysfunction in diabetes mellitus.

Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration

“…Dameni et al (2018) carried out their study in a chronic constriction injury model in male rats and found that acute administration of irisin increased pain threshold; however, irisin could not prevent the decline in the number of neurons [ 105 ]. Wang et al (2018) reported on the basis of their study in primary cell cultures of astrocytes and neurons that a pretreatment of astrocyte-conditioned medium with irisin for about 12 h protected neurons from the toxicity of amyloid-β [ 106 ]. Irisin could also attenuate the release of IL-6 and IL-1β from cultured astrocytes and reduced expression of COX-2 and phosphorylation of AKT [ 106 ].…”

“…Wang et al (2018) reported on the basis of their study in primary cell cultures of astrocytes and neurons that a pretreatment of astrocyte-conditioned medium with irisin for about 12 h protected neurons from the toxicity of amyloid-β [ 106 ]. Irisin could also attenuate the release of IL-6 and IL-1β from cultured astrocytes and reduced expression of COX-2 and phosphorylation of AKT [ 106 ]. In addition, irisin could decrease NFκB activation of astrocytes exposed to amyloid-β by preventing phosphorylation and loss of IκBα [ 106 ].…”

“…Irisin could also attenuate the release of IL-6 and IL-1β from cultured astrocytes and reduced expression of COX-2 and phosphorylation of AKT [ 106 ]. In addition, irisin could decrease NFκB activation of astrocytes exposed to amyloid-β by preventing phosphorylation and loss of IκBα [ 106 ]. Thus, irisin is supposed to be have a novel application in the treatment of AD and memory dysfunction in diabetes mellitus in the future [ 106 ].…”

“…In addition, irisin could decrease NFκB activation of astrocytes exposed to amyloid-β by preventing phosphorylation and loss of IκBα [ 106 ]. Thus, irisin is supposed to be have a novel application in the treatment of AD and memory dysfunction in diabetes mellitus in the future [ 106 ].…”

Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy

“…In a middle cerebral artery occlusion mouse model, irisin was reported to protect against cerebral ischemia-induced neuronal injury by reducing oxidative stress, suppress inflammation by reducing plasma TNFα and IL-6, inhibit the activation of Iba1 + microglia, and infiltrate MPO-1 + monocytes [ 25 ]. Irisin inhibits not only microglial activation but also NF-κB activation in cultured astrocytes, thereby reducing downstream COX-2 expression and releasing IL-6 and IL-1β [ 26 ]. Another study demonstrated its neuroprotective effect in cerebral ischemia/reperfusion injury by irisin-induced reduction in the activation of apoptosis and TNFα and IL-1β expression in brain tissue [ 27 ].…”