Irisin Attenuates Neuroinflammation and Prevents the Memory and Cognitive Deterioration in Streptozotocin-Induced Diabetic Mice

Abstract

Diabetes mellitus (DM) patients experience memory and cognitive deficits. The mechanisms underlying this dysfunction in the brain of DM patients are not fully understood, and therefore, no optimized therapeutic strategy has been established so far. The aim of the present study was to assess whether irisin was able to improve memory and cognitive performance in a streptozotocin-induced diabetic mouse model. A diabetic mouse model was established and behavioral tests were performed. We also set up primary cultures for mechanism studies. Western blots and EMSA were used for molecular studies. Significant impairment of cognition and memory was observed in these DM mice, which could be effectively prevented by irisin cotreatment. We also found upregulated levels of GFAP protein, reduced synaptic protein expression, and increased levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the brains; however, irisin significantly attenuated these cellular responses. Meanwhile, our results demonstrated that irisin inhibited the activation of P38, STAT3, and NFκB proteins of DM mice. Furthermore, our results suggested that irisin might regulate the function of P38, STAT3, and NFκB in hippocampal tissues of DM mice. Collectively, irisin inhibited neuroinflammation in STZ-induced DM mice by inhibiting cytokine release and improving their cognitive function. Our findings revealed the mechanism of irisin’s anti-inflammatory effect in the CNS.

Melatonin prevents diabetes‐associated cognitive dysfunction from microglia‐mediated neuroinflammation by activating autophagy via TLR4/Akt/mTOR pathway

“…A growing body of evidence suggests that diabetes is associated with cognitive decline, and the level of hyperglycemia and the duration of diabetes are linked with cognitive decline 21 . Previous studies have reported that oxidative stress, energy metabolism disorders, and neuroinflammation may be the underlying pathogenesis of diabetes‐associated cognitive decline 22‐24 . Some studies have indicated that MLT has a regulatory effect on oxidative stress and energy metabolism 11,25 .…”

The Novel Perspectives of Adipokines on Brain Health

“…Previous studies focus on the acute action of leptin on synaptic plasticity, whereas recent studies report insulin resistance afflicts circulating leptin levels and affects central neuroplasticity and cognitive functions. Besides, animal studies have demonstrated a possible link between metabolic disorders with aberrant circulating adipokine levels and cognitive behavioral deficits [34,35,36,37,38] or neuropathology [39,40,41].…”

Exercise–Linked Irisin: Consequences on Mental and Cardiovascular Health in Type 2 Diabetes

“…Regarding animal studies, Wang et al, assessed whether irisin was able to improve memory and cognitive performance in a diabetic mouse model [ 76 ]. The authors used 8-week-old male C57BL/6 for this study.…”