Tilapia Skin Peptides Ameliorate Cyclophosphamide-Induced Anxiety- and Depression-Like Behavior via Improving Oxidative Stress, Neuroinflammation, Neuron Apoptosis, and Neurogenesis in Mice

Abstract

Anxiety- and depression-like behavior following chemotherapy treatment occurs in cancer patients with high probability and no specific therapeutics are available for treatment and prevention of this complication. Here, tilapia skin peptides (TSP), a novel enzymatically hydrolyzed bioactive peptide mixture, obtained from tilapia (Oreochromis mossambicus) scraps, were studied on cyclophosphamide (CP)-induced anxiety- and depression-like behavior in mice. Mice were received intraperitoneal injection of CP for 2 weeks, while TSP was administered for 4 weeks. After the end of the animal experiment, behavioral, biochemical, and molecular tests were carried out. The mice decreased preference for sugar water, increased immobility time in the forced swimming and tail suspension test, and decreased travel distance in the open field test in the Model group, compared with the Control group. Abnormal changes in behavioral tests were significantly improved after the TSP treatment. Additionally, abnormalities on superoxide dismutase, malondialdehyde, glutathione peroxidase were rescued by administration of 1000 mg/kg/d TSP in mice than that of the Model group. TSP has normalized the expression of Iba-1 and the levels of TNF-α and IL-1β in the hippocampus of mice, which indicated that TSP could observably ameliorate neuroinflammatory response in the hippocampus of mice. TSP ameliorated the apoptosis of hippocampal neurons of CA1 and CA3 regions in the TSP group vs. the Model group. The number of doublecortin positive cells was drastically increased by administering 1000 mg/kg/d TSP in mice vs. the Model group. Furthermore, TSP reversed the Nrf2/HO-1 signaling pathway, BDNF/TrkB/CREB signaling pathway, and reduced the Bcl-2/Bax/caspase-3 apoptosis pathway. In conclusion, TSP could restore CP-induced anxiety- and depression-like behavior via improving oxidative stress, neuroinflammation, neuron apoptosis, and neurogenesis in mice hippocampus.

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies

“…Studies were consistent in measuring cyclic AMP responsive element binding protein (CREB) activity, in that increased phospho-CREB or CREB levels were associated with an antidepressant response [ 38 , 46 , 81 , 83 , 103 , 109 , 112 ]; remarkably, studies on peripheral tissues in man [ 38 ] and hippocampal content in mice [ 81 ] pointed to the same direction. Additionally, studies of BDNF showed that increased BDNF activity was associated with antidepressant effects and that animals displaying depressive features have low BDNF contents in the periphery and the brain [ 44 , 52 , 57 , 57 , 58 , 66 , 67 , 69 , 81 , 83 , 85 , 88 , 93 , 111 , 112 , 114 , 121 ]. It has recently been shown that most, if not all, antidepressant drugs bring about their antidepressant effects by binding the tyrosine kinase receptor 2 (TrkB), a molecule tied to the action of BDNF [ 127 , 128 ].…”

DHA- and EPA-Enriched Phosphatidylcholine Suppress Human Lung Carcinoma 95D Cells Metastasis via Activating the Peroxisome Proliferator-Activated Receptor γ

“…Images were photographed under a fluorescence confocal microscope. The experimental method referred to the previous studies with appropriately modified [ 31 , 32 ].…”

Marine natural products: potential agents for depression treatment

“…A significant number of MNPs are produced by the complex living environment of marine animals, and a novel entity structure and enormous diversity are provided by the chemical structure with strong biological activity ( Zhao et al, 2022a ). Some MNPs have participated in antidepressant preclinical or clinical trials and have proven to be great sources for novel and effective antidepressants ( Tables 1 , 2 ).…”

“…Some MNPs have participated in antidepressant preclinical or clinical trials and have proven to be great sources for novel and effective antidepressants ( Tables 1 , 2 ). The marine environment is a rich source of novel pharmaceuticals, many of the substances found there can regulate brain activity, reduce anxiety, and have potential therapeutic applications for disorders associated with anxiety and depression ( Zhao et al, 2022a ). At present, with the interaction between academia and the pharmaceutical sector, a large number of MNPs have been discovered and tested using current analytical methods.…”