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      Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice

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          Abstract

          Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.

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          Most cited references49

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          Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.

          Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases.
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            Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease.

            Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote AD-like pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-beta protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-beta precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of Abeta, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.
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              The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study.

              An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem). Naps with increased spindles produced significantly better verbal memory and significantly worse perceptual learning but did not affect motor learning. The experimental spindles were similar to control spindles in amplitude and frequency, suggesting that the experimental intervention enhanced normal sleep processes. Furthermore, using statistical methods, we demonstrate for the first time a critical role of spindles in human hippocampal memory performance. The gains in memory consolidation exceed sleep-alone or control conditions and demonstrate the potential for targeted, exceptional memory enhancement in healthy adults with pharmacologically modified sleep.
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                Author and article information

                Journal
                Exp Anim
                Exp. Anim
                EXPANIM
                Experimental Animals
                Japanese Association for Laboratory Animal Science
                1341-1357
                1881-7122
                6 November 2015
                2016
                : 65
                : 1
                : 97-107
                Affiliations
                [1) ]Laboratorio de Microscopia de Alta Resolución, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. Jalisco, 44340, Mexico
                [2) ]Instituto Tecnológico y de Estudios Superiores. Guadalajara, Jalisco, Mexico
                [3) ]Laboratorio de Neurociencias, Facultad de Psicología, Universidad de Colima, Colima, 28040, Mexico
                Author notes
                Address corresponding: R.E. Gonzalez Castañeda, Neuroscience Department, Universidad de Guadalajara, Sierra Mojada No. 950, Guadalajara, Jal. 44340, Mexico
                Article
                15-0054
                10.1538/expanim.15-0054
                4783655
                26548630
                d6869d6e-27d0-4552-a4b4-80963fa42822
                ©2016 Japanese Association for Laboratory Animal Science

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

                History
                : 01 June 2015
                : 23 September 2015
                Categories
                Original

                anxiety,depression,female,male,sex-dependent effect,sleep disorder

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