Adolescent co-exposure to environmental cadmium and high-fat diet induces cognitive decline via Larp7 m6A-mediated SIRT6 inhibition.

The effects and underlying mechanisms of adolescent exposure to combined environmental hazards on cognitive function remain unclear. Here, using a combined exposure model, we found significant cognitive decline, hippocampal neuronal damage, and neuronal senescence in mice exposed to cadmium (Cd) and high-fat diet (HFD) during adolescence. Furthermore, we observed a significant downregulation of Sirtuin 6 (SIRT6) expression in the hippocampi of co-exposed mice. UBCS039, a specific SIRT6 activator, markedly reversed the above adverse effects. Further investigation revealed that co-exposure obviously reduced the levels of La ribonucleoprotein 7 (LARP7), disrupted the interaction between LARP7 and SIRT6, ultimately decreasing SIRT6 expression in mouse hippocampal neuronal cells. Overexpression of Larp7 reversed the combined exposure-induced SIRT6 decrease and senescence in mouse hippocampal neuronal cells. Additionally, the results showed notably elevated levels of Larp7 m6A and YTH domain family protein 2 (YTHDF2) in mouse hippocampal neuronal cells treated with the combined hazards. Ythdf2 short interfering RNA, RNA immunoprecipitation, and RNA stability assays further demonstrated that YTHDF2 mediated the degradation of Larp7 mRNA under combined exposure. Collectively, adolescent co-exposure to Cd and HFD causes hippocampal senescence and cognitive decline in mice by inhibiting LARP7-mediated SIRT6 expression in an m6A-dependent manner.

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus.

BACKGROUND: Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. METHODS: Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. RESULTS: There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. CONCLUSIONS: The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Effects of maternal stress during pregnancy on learning and memory via hippocampal BDNF, Arc (Arg3.1) expression in offspring.

The intrauterine environment has a significant long-term impact on individual's life, this study was designed to investigate the effect of stress during pregnancy on offspring's learning and memory abilities and analyze its mechanisms from the expression of BDNF and Arc in the hippocampus of the offspring. A rat model of maternal chronic stress during pregnancy was mating from 3rd day during been subjecting to chronic unpredictable mild stress (CUMS). The body weights and behavioral changes were recorded, and plasma corticosterone levels were determined by radioimmunoassay. The learning and memory abilities of the offspring were measured by Morris water maze testing from PND 42. The expression of hippocampal BDNF and Arc mRNA and protein were respectively measured using RT-PCR and Western blotting. Results indicated that an elevation was observed in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy, a reduction in the crossing and rearing movement times and the preference for sucrose. The body weight of maternal stress's offspring was lower than the control group, and the plasma corticosterone level was increased. Chronic stress during pregnancy had a significant impact on the spatial learning and memory of the offspring. The expression of BDNF mRNA and protein, Arc protein in offspring of maternal stress during pregnancy was attenuated and some relationships existed between these parameters. Collectively, these findings disclose that long-time maternal stress during pregnancy could destroy spatial learning and memory abilities of the offspring, the mechanism of which is related to been improving maternal plasma corticosterone and reduced hippocampal BDNF, Arc of offspring rats.

Chronic unpredictable mild stress impairs erythrocyte immune function and changes T-lymphocyte subsets in a rat model of stress-induced depression.

Stress has been shown to suppress immune function and increase susceptibility to inflammatory and psychiatric diseases. This study sought to investigate the changes in erythrocyte immune functions and T-lymphocyte subsets and to explore the mechanism implicated in the process of stress-induced depression by employing a rat depression model induced by chronic unpredictable mild stress (CUMS). The body weights and behavioral changes of the rats were recorded, and plasma corticosterone levels were determined by radioimmunoassay. Erythrocyte immune function and T-lymphocytes subsets were respectively measured by the method of yeast rosette and flow cytometry at different time intervals, and their relationship was analyzed. Results indicated that a reduction was observed in the following: the rats' crossing and rearing movement times, the volume of sucrose intake and the preference for sucrose in the depression model group. Plasma corticosterone levels were elevated; the rate of E-C3bR decreased, and E-IC was increased. Some alterations in the percentage of T-lymphocytes and IL-2 appeared in the depression model group and some relationships existed between these parameters. Collectively, these findings disclose that long-time stress could induce changes in rat behavior and activities through an effect on erythrocyte immune functions and T-lymphocyte subsets.

[Red blood cell on lymphocyte proliferation in rats with chronic unpredictable mild stress].

OBJECTIVE: To study the changes of rat red blood cells on T, B lymphocytes proliferation in chronic unpredictable mild stress (CUMS). METHODS: Thirty Wistar rats were averagely divided into control group and the CUMS group. The relevant behavioral performance and red blood cells on lymphocytes proliferation Changes by MTT colorimetric were observed. RESULTS: After fourteen days, the growth of weight and organic coefficient of brain decreased in model group (P < 0.05), with a significantly reduced consumption and preference of sucrose solutions, and increased pure water consumption as compared with control group (P < 0.05). Plasma corticosterone levels peaked at seven days but on a declining trend after fourteen days. The rate of red blood cells on T, B lymphocyte proliferation in depression group was lower than non-stress in 7, 14, 21 days (P < 0.05). CONCLUSION: The repeated chronic mild stress stimulation can induce long-time changes in acts and activities and decrease the rate of red blood cells on T, B lymphocytes proliferation, which can provide a new experimental method to observe the red blood cell immune function under the stress.