Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Time interval for booster vaccination following reexposure to rabies in previously vaccinated subjects.

Background: In rabies endemic areas, re-exposures to rabies are quite common and the incidence could be up to 15%. The recent guidelines of World Health Organization do not specify the duration of protection provided by previous pre- or post exposure prophylaxis. This often puts the treating physician in a dilemma in such cases of re-exposure. Objective: Study the time interval between primary and booster vaccination in individuals who have taken previously a full course of either pre- or post exposure prophylaxis and are now re-exposed to rabies. Methods: The data obtained through a literature search using Pubmed and advanced Google search along with data from in house clinical trials were used for analysis. Sixty-six vaccine cohorts spanning more than 27 years from 1983 to 2010 from six countries were studied. The duration of protection offered by previous vaccination was assessed by using a surrogate marker of adequate (> 0.5 IU per mL) rabies virus neutralizing antibody levels in the individuals vaccinated either by pre-exposure or post exposure regimens received by intramuscular or intradermal routes. Results: The proportions of 2,795 subjects who had received prior post-exposure immunization and produced rabies virus neutralizing antibody levels of less than 0.5 IU per mL were 0.07% and 0.14% at the end of the first and third month post primary vaccination. All 577 subjects with previous pre-exposure vaccination had antibody responses above 0.5 IU per mL at the end of the first and third month post primary vaccination. Conclusion: We concluded that it may be safe for up to three months after previous pre- or post exposure vaccination to not administer boosters to healthy subjects who have been re-exposed to rabies.

Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress / 中华行为医学与脑科学杂志

Objective To investigate behavior and hippocampal cytoskeletal alterations following re-exposure to chronic unpredictable mild stress(CUMS) and acute swimming stress,and explore the possible mechanism.Methods 40 Male Sprague-Dawley (SD) rats were divided into five groups,with 8 exposed to 21 consecutive days of chronic unpredicted mild stresses (CUMS) and treated with vehicle,8 exposed to CUMS and treated with fluoxetine,8 exposed to CUMS and treated with fluoxetine and re-exposed to acute swimming stress after washout,8 exposed to CUMS and treated with fluoxetine and re-exposed to CUMS after washout,and 8 as normal controls treated with vehicle.Behavioral changes in these rats were analyzed.The expressions of hippocampal cytoskeletal microtubulin were analyzed using Western Blot.Results ( 1 ) Compared with the control and CUMS group,sucrose preference (43.38 ± 7.84 ) ％,total traveling distance ( 859.21 ± 653.62 ) cm,velocity ( 2.05 ± 0.60 ) cm/s and frequencies of rearing(0.12 ±0.30) were reduced (P＜0.01 ) in the re-exposure to CUMS group.After re-exposed to acute stress,these behaviors did not differ from control rats.(2)Compared with the control and CUMS group,the Acet-Tub expression (244.24 ± 8.90 )％ of re-exposure to CUMS group showed a significant increase (P＜ 0.01 ) in rats submitted to re-exposure to CUMS and Tyr-Tub expression (30.92 ± 11.01 )％ was significantly decreased following re-exposure to CUMS (P＜0.01).At the same time,MAP-2 expression did not change while phospho-MAP-2 expression (24.75 ± 8.83 )％ decreased significantly.After re-exposed to acute stress,these prorein expressions did not differ from control rats.Conclusion These findings provide evidence that rats re-exposed to CUMS showed more impairment of cytoskeletal microtubular dynamic and structural neuronal plasticity,this effect appears to be mediated by the degree of phosphorylation of MAP-2.