Melatonin restores hippocampal neural precursor cell proliferation and prevents cognitive deficits induced by jet lag simulation in adult mice

Abstract

Frequent flyers and shift workers undergo circadian dysrhythmia with adverse impact on body and mind. The circadian rhythm disorder "jet lag" disturbs hippocampal neurogenesis and spatial cognition, which represent morphological and functional adult brain plasticity. This raises the question if pro-neurogenic stimuli might prevent those consequences. However, suitable measures to mitigate jet lag-induced adverse effects on brain plasticity have been neglected so far. Here, we used adult C57Bl6 mice to investigate the pro-neurogenic stimuli melatonin (8 mg/kg i.p.) as well as environmental enrichment as potential measures. We applied photoperiod alterations to simulate "jet lag" by shortening the dark period every third day by 6 hours for 3 weeks. We found that "jet lag" simulation reduced hippocampal neural precursor cell proliferation by 24% and impaired spatial memory performance in the water maze indicated by a prolonged swim path to the target (~23%). While melatonin prevented both the cellular (~1%) as well as the cognitive deficits (~5%), environmental enrichment only preserved precursor cell proliferation (~12%). Our results indicate that lifestyle interventions are insufficient to completely compensate jet lag-induced consequences. Instead, melatonin is required to prevent cognitive impairment caused by the same environmental factors to which frequent flyers and shift workers are typically exposed to.

Melatonin ameliorates cuprizone‐induced reduction of hippocampal neurogenesis, brain‐derived neurotrophic factor, and phosphorylation of cyclic AMP response element‐binding protein in the mouse dentate gyrus

“…Melatonin has an antioxidative property and scavenges free radicals more effectively than do vitamins C and E (Korkmaz et al, ; Pieri, Marra, Moroni, Recchioni, & Marcheselli, ). Melatonin has positive effects about the hippocampus‐dependent cognitive function (Chen et al, ) as well as the hippocampal neurogenesis (Iggena, Winter, & Steiner, ; Yoo, Kim, Lee, et al, ; ). Additionally, it increases the number of proliferating cells and neuroblasts in the dentate gyrus of aged mice induced by D‐galactose treatment (Yoo, Kim, Lee, et al, ; ).…”

“…Melatonin has positive effects about the hippocampus-dependent cognitive function (Chen et al, 2017) as well as the hippocampal neurogenesis (Iggena, Winter, & Steiner, 2017;Yoo, Kim, Lee, et al, 2012;). Additionally, it increases the number of proliferating cells and neuroblasts in the dentate gyrus of aged mice induced by Dgalactose treatment (Yoo, Kim, Lee, et al, 2012;).…”

NR4A1 Promotes Diabetic Nephropathy by Activating Mff-Mediated Mitochondrial Fission and Suppressing Parkin-Mediated Mitophagy

“…However, these authors argued that activated NR4A1 due to high-fat diets mediates Drp1 phosphorylation and represses Bnip3 transcription, leading to fission activation and mitophagy inhibition. Other signaling pathways may also be involved in simultaneously regulating fission and mitophagy [70,71]. In cardiac microvascular ischemia reperfusion, DUSP1 has been shown to repress fission and recuse mitophagy via the JNK pathway [17,72].…”

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

“…Samples were then directly examined by confocal microscopy using the ×40 1.42 NA oil immersion objective. For quantification of the concentrations change of [Ca 2+ ]c, flow cytometry was used [37]. For analysis of [Ca 2+ ]m, Rhod-2 (Molecular Probes) was used and the images were captured by confocal microscopy.…”