Sex differences in cognition following variations in endocrine status.

Spatial memory, mediated primarily by the hippocampus, is responsible for orientation in space and retrieval of information regarding location of objects and places in an animal's environment. Since the hippocampus is dense with steroid hormone receptors and is capable of robust neuroplasticity, it is not surprising that changes in spatial memory performance occur following a variety of endocrine alterations. Here, we review cognitive changes in both spatial and nonspatial memory tasks following manipulations of the hypothalamic-pituitary-adrenal and gonadal axes and after exposure to endocrine disruptors in rodents. Chronic stress impairs male performance on numerous behavioral cognitive tasks and enhances or does not impact female cognitive function. Sex-dependent changes in cognition following stress are influenced by both organizational and activational effects of estrogen and vary depending on the developmental age of the stress exposure, but responses to gonadal hormones in adulthood are more similar than different in the sexes. Also discussed are possible underlying neural mechanisms for these steroid hormone-dependent, cognitive effects. Bisphenol A (BPA), an endocrine disruptor, given at low levels during adolescent development, impairs spatial memory in adolescent male and female rats and object recognition memory in adulthood. BPA's negative effects on memory may be mediated through alterations in dendritic spine density in areas that mediate these cognitive tasks. In summary, this review discusses the evidence that endocrine status of an animal (presence or absence of stress hormones, gonadal hormones, or endocrine disruptors) impacts cognitive function and, at times, in a sex-specific manner.

E-cigarette sharing behavior among college students: An exploratory study.

INTRODUCTION: The purpose of this study was to explore sharing behavior among college students who use e-cigarettes. METHODS: A convenience sample of current e-cigarette users answered questionnaire items regarding sharing behavior (e.g., the number of people that have shared e-cigarettes, the settings that sharing takes place, reasons for sharing). RESULTS: Of the 121 participants, 24% shared e-cigarettes every day and 76% shared some days. The most common setting (91%) for sharing was at social gatherings, and participants shared most often (52%) with one or two people, which happened most often (99%) with friends. The top reason (80%) for sharing e-cigarettes was to feel the effects of nicotine. CONCLUSIONS: The finds support the need to address sharing behavior in youth e-cigarette use and the need for more stringent e-cigarette policies and cessation resources.

A potential role for dendritic spines in bisphenol-A induced memory impairments during adolescence and adulthood.

Developmental exposure to Bisphenol A (BPA), an endocrine disrupting chemical, alters many behaviors and neural parameters in rodents and non-human-primates. The effects of BPA are mediated via gonadal hormone, primarily, estrogen receptors, and are not limited to the perinatal period since recent studies show impairments further into development. The studies described in this chapter address the effects of BPA administration during early adolescence on memory and dendritic spine density in intact male and female rats as well as ovariectomized (OVX) rats in late adolescence and show that some of these adolescent induced changes endure into adulthood. In general, BPA impairs spatial memory and induces decreases in dendritic spine density in the hippocampus and the medial prefrontal cortex, two areas important for memory. The effects of adolescent BPA in intact females are compared to OVX females in an attempt to address the importance of estrogens in the mechanism(s) underlying the profound neuronal alterations occurring during adolescent development. In addition, potential mechanisms by which acute and chronic BPA induce structural alterations are discussed. These studies suggest a complex interaction between low doses of BPA, gonadal state and neural development.

Effects of adolescent Bisphenol-A exposure on memory and spine density in ovariectomized female rats: Adolescence vs adulthood.

The endocrine disruptor, Bisphenol-A (BPA), alters many behavioral and neural parameters in rodents. BPA administration to gonadally intact adolescent rats increases anxiety, impairs spatial memory, and decreases dendritic spine density when measured in adulthood. Since BPA's action seems to be mediated through gonadal steroid receptors, the current experiments were done in ovariectomized (OVX) female rats to examine the effects on behavior and spine density of adolescent BPA exposure under controlled hormone conditions. OVX (postnatal day, PND, 21) female Sprague-Dawley rats (n = 66) received subcutaneous injections of BPA (40 µg/kg/bodyweight), 17ß-Estradiol (E2, 50 µg/kg/bodyweight), or saline during adolescence (PND 38-49). Following the last injection brains were processed for Golgi impregnation (Exp1), behavioral and spine density in adolescence (Exp2), or in adulthood (Exp3). In Exp1, E2 increased spine density in CA1 pyramidal cells and BPA decreased spine density in granule cells of the dentate gyrus (DG). In Exp2, BPA impaired spatial memory on the object placement (OP) task, E2 increased spine density in CA1, BPA decreased spine density in the DG and the medial prefrontal cortex (mPFC). When measured in adulthood (Exp3), BPA impaired OP and object recognition (OR) performance, E2 increased spine density in CA1, and BPA decreased spine density in CA1, the mPFC and the DG. Results provide novel data on the effects of adolescent BPA in an OVX model and are compared to data in intact animals and within the context of understanding the importance of the profound neuronal alterations occurring during adolescent development.

Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders.

The molecular basis for the majority of cases of autism spectrum disorders (ASD) remains unknown. We tested the hypothesis that ASD have an epigenetic cause by performing DNA methylation profiling of five CpG islands (CGI-1 to CGI-5) in the SHANK3 gene in postmortem brain tissues from 54 ASD patients and 43 controls. We found significantly increased overall DNA methylation (epimutation) in three intragenic CGIs (CGI-2, CGI-3 and CGI-4). The increased methylation was clustered in the CGI-2 and CGI-4 in ∼15% of ASD brain tissues. SHANK3 has an extensive array of mRNA splice variants resulting from combinations of five intragenic promoters and alternative splicing of coding exons. Altered expression and alternative splicing of SHANK3 isoforms were observed in brain tissues with increased methylation of SHANK3 CGIs in ASD brain tissues. A DNA methylation inhibitor modified the methylation of CGIs and altered the isoform-specific expression of SHANK3 in cultured cells. This study is the first to find altered methylation patterns in SHANK3 in ASD brain samples. Our finding provides evidence to support an alternative approach to investigating the molecular basis of ASD. The ability to alter the epigenetic modification and expression of SHANK3 by environmental factors suggests that SHANK3 may be a valuable biomarker for dissecting the role of gene and environment interaction in the etiology of ASD.

Functional aspects of estrogen neuroprotection.

Evidence that estrogen protects neurons against toxic/ ischemic insults or degenerative/aging processes is evident in a variety of in vitro and in vivo systems. However, a critical remaining question is: Does the demonstrated morphologic and neurochemical protection by estrogen lead to a preservation of brain function or an enhanced ability to recover? To date, little basic research is available on this issue. Cognition is a critical function that might provide a sensitive way to examine this question. As a first step, we present results showing that two chronic environmental insults, psychoactive drugs and stress, produce gender-specific responses in cognitive abilities. Specifically, females appear less sensitive than males to cognitive impairments following chronic exposure to these factors. Results are presented in male and female rats utilizing cognitive tests that assess visual (object recognition) and spatial memory (object placement and radial arm maze) following chronic amphetamine, methamphetamine, or daily restraint stress. Following regimes of chronic stress or amphetamine, males were impaired on these tasks while females were either unaffected, less affected, or enhanced in performance. These observations suggest that differences in circulating gonadal hormone levels between the sexes may contribute to the differential sensitivity of the sexes and provide endogenous neuroprotection for females. Surprisingly, ovariectomized females were still not impaired following a stress regimen that impaired males (21 d of daily restraint). These data taken together with neurochemical data on estrogen neuroprotective effects indicate that it is possible that neuroprotection by estrogen may result from hormone action both during sexual differentiation (organizational effect) and in adulthood (activational effect). These considerations and possible unwanted/untoward effects of chronic estrogen use are discussed in relation to the use of selective estrogen receptor modulators for chronic treatment of both males and females. In conclusion, although compelling evidence for neuroprotection by estrogen has been presented in anatomic and neurochemical studies, it is clear that the functional/ behavioral aspects need further investigation.