Apoptosis-induced decline in hippocampal microglia mediates the development of depression-like behaviors in adult mice triggered by unpredictable stress during adolescence.

Depression triggered by harmful stress during adolescence is a common problem that can affect mental health. To date, the mechanisms underlying this type of depression remain unclear. One mechanism for the promotion of depression by chronic stress in adulthood is the loss of hippocampal microglia. Since deleterious stress in adolescence also activates microglia, we investigated the dynamic changes of microglia in the hippocampus in mice exposed to chronic unpredictable stress (CUS) in adolescence. Our results showed that 12 days of CUS stimulation in adolescence induced typical depression-like behaviors in adult mice, which were accompanied by a significant decrease and dystrophy of microglia in the dentate gyrus of the hippocampus. Further analysis showed that this decrease in microglia was mediated by the initial response of microglia to unpredictable stress in the dentate gyrus of the hippocampus and their subsequent apoptosis. Blocking the initial response of microglia to unpredictable stress by pretreatment with minocycline was able to prevent apoptosis and microglial decline as well as the development of depression-like behaviors in adult mice induced by adolescent CUS. Moreover, administration of lipopolysaccharide (LPS) or macrophage-colony stimulatory factor (M-CSF), two drugs that reversed microglia decline in the dentate gyrus, ameliorated the depression-like behaviors induced by CUS stimulation in adolescence. These findings reveal a novel mechanism for the development of depression-like behaviors in animals triggered by deleterious stress in adolescence and suggest that reversing microglial decline in the hippocampus may be a hopeful strategy for the treatment of depression triggered by deleterious stress in adolescence.

Neuroprotective effects of anthocyanins and its major component cyanidin-3-O-glucoside (C3G) in the central nervous system: An outlined review.

Anthocyanins, a class of water soluble flavonoids extracted from plants like berries and soybean seed, have been shown to display obvious anti-oxidative, anti-inflammatory, and anti-apoptotic activities. They are recommended as a supplementation for prevention and/or treatment of disorders ranging from cardiovascular disease, metabolic syndrome, and cancer. In the central nervous system (CNS), anthocyanins and its major component cyanidin-3-O-glucoside (C3G) have been reported to produce preventive and/or therapeutic activities in a wide range of disorders, such as cerebral ischemia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and glioblastoma. Both anthocyanins and C3G can also affect some important processes in aging, including neuronal apoptosis and death as well as learning and memory impairment. Further, the anthocyanins and C3G have been shown to prevent neuro-toxicities induced by different toxic factors, such as lipopolysaccharide, hydrogen peroxide, ethanol, kainic acid, acrolein, glutamate, and scopolamine. Mechanistic studies have shown that inhibition of oxidative stress and neuroinflammation are two critical mechanisms by which anthocyanins and C3G produce protective effects in CNS disorder prevention and/or treatment. Other mechanisms, including suppression of c-Jun N-terminal kinase (JNK) activation, amelioration of cellular degeneration, activation of the brain-derived neurotrophic factor (BDNF) signaling, and restoration of Ca2+ and Zn2+ homeostasis, may also mediate the neuroprotective effects of anthocyanins and C3G. In this review, we summarize the pharmacological effects of anthocyanins and C3G in CNS disorders as well as their possible mechanisms, aiming to get a clear insight into the role of anthocyanins in the CNS.