Pregnancy history and estradiol influence spatial memory, hippocampal plasticity, and inflammation in middle-aged rats.

Pregnancy and motherhood can have long-term effects on cognition and brain aging in both humans and rodents. Estrogens are related to cognitive function and neuroplasticity. Estrogens can improve cognition in postmenopausal women, but the evidence is mixed, partly due to differences in age of initiation, type of menopause, dose, formulation and route of administration. Additionally, past pregnancy influences brain aging and cognition as a younger age of first pregnancy in humans is associated with poorer aging outcomes. However, few animal studies have examined specific features of pregnancy history or the possible mechanisms underlying these changes. We examined whether maternal age at first pregnancy and estradiol differentially affected hippocampal neuroplasticity, inflammation, spatial reference cognition, and immediate early gene activation in response to spatial memory retrieval in middle-age. Thirteen-month-old rats (who were nulliparous (never mothered) or previously primiparous (had a litter) at three or seven months) received daily injections of estradiol (or vehicle) for sixteen days and were tested on the Morris Water Maze. An older age of first pregnancy was associated with impaired spatial memory but improved performance on reversal training, and increased number of new neurons in the ventral hippocampus. Estradiol decreased activation of new neurons in the dorsal hippocampus, regardless of parity history. Estradiol also decreased the production of anti-inflammatory cytokines based on age of first pregnancy. This work suggests that estradiol affects neuroplasticity and neuroinflammation in middle age, and that age of first pregnancy can have long lasting effects on hippocampus structure and function.

Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging.

BACKGROUND AND OBJECTIVES: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition. METHODS: We used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes, smoking, and obesity. Cognition was measured with a global cognitive composite at baseline and 3-year follow-up. Linear models tested independent and interactive associations of age at menopause, vascular risk, and HT history with cognition at 3-year follow-up, adjusting for baseline cognition, baseline age, years of education, and test language (English/French). RESULTS: We included 8,360 postmenopausal female participants (mean age at baseline = 65.0 ± 8.53 years, mean age at menopause = 50.1 ± 4.62 years) and 8,360 age-matched male participants for comparison. There was an interaction between age at menopause and vascular risk, such that earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores at follow-up (ß = 0.013, 95% CI 0.001-0.025, p = 0.03). In stratified analyses, vascular risk was associated with lower cognitive scores in female participants with earlier menopause (menopausal ages 35-48 years; ß = -0.044, 95% CI -0.066 to -0.022, p < 0.001), but not average (ages 49-52 years; ß = -0.007, 95% CI -0.027 to 0.012, p = 0.46) or later menopause (ages 53-65 years; ß = 0.003, 95% CI -0.020 to 0.025, p = 0.82). The negative association of vascular risk with cognition in female participants with earlier menopause was stronger than the equivalent association in age-matched male participants. HT history did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (ß = -0.005, 95% CI -0.032 to 0.021, p = 0.69). DISCUSSION: Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in female adults. These findings have implications for the development of sex-specific dementia prevention strategies.

Beyond sex differences: short- and long-term effects of pregnancy on the brain.

Growing attention has been directed to the inclusion of females in neuroscience studies, and to the importance of studying sex as a biological variable. However, how female-specific factors such as menopause and pregnancy, affect the brain remains understudied. In this review, we use pregnancy as a case in point of a female-unique experience that can alter neuroplasticity, neuroinflammation, and cognition. We examine studies in both humans and rodents indicating that pregnancy can modify neural function in the short term, as well as alter the trajectory of brain aging. Furthermore, we discuss the influence of maternal age, fetal sex, number of pregnancies, and presence of pregnancy complications on brain health outcomes. We conclude by encouraging the scientific community to prioritize researching female health by recognizing and including factors such as pregnancy history in research.

Detection of Emotion of Speech for RAVDESS Audio Using Hybrid Convolution Neural Network.

Every human being has emotion for every item related to them. For every customer, their emotion can help the customer representative to understand their requirement. So, speech emotion recognition plays an important role in the interaction between humans. Now, the intelligent system can help to improve the performance for which we design the convolution neural network (CNN) based network that can classify emotions in different categories like positive, negative, or more specific. In this paper, we use the Ryerson Audio-Visual Database of Emotional Speech and Song (RAVDESS) audio records. The Log Mel Spectrogram and Mel-Frequency Cepstral Coefficients (MFCCs) were used to feature the raw audio file. These properties were used in the classification of emotions using techniques, such as Long Short-Term Memory (LSTM), CNNs, Hidden Markov models (HMMs), and Deep Neural Networks (DNNs). For this paper, we have divided the emotions into three sections for males and females. In the first section, we divide the emotion into two classes as positive. In the second section, we divide the emotion into three classes such as positive, negative, and neutral. In the third section, we divide the emotions into 8 different classes such as happy, sad, angry, fearful, surprise, disgust expressions, calm, and fearful emotions. For these three sections, we proposed the model which contains the eight consecutive layers of the 2D convolution neural method. The purposed model gives the better-performed categories to other previously given models. Now, we can identify the emotion of the consumer in better ways.

Steroid hormones and hippocampal neurogenesis in the adult mammalian brain.

Hippocampal neurogenesis persists across the lifespan in many species, including rodents and humans, and is associated with cognitive performance and the pathogenesis of neurodegenerative disease and psychiatric disorders. Neurogenesis is modulated by steroid hormones that change across development and differ between the sexes in rodents and humans. Here, we discuss the effects of stress and glucocorticoid exposure from gestation to adulthood as well as the effects of androgens and estrogens in adulthood on neurogenesis in the hippocampus. Throughout the review we highlight sex differences in the effects of steroid hormones on neurogenesis and how they may relate to hippocampal function and disease. These data highlight the importance of examining age and sex when evaluating the effects of steroid hormones on hippocampal neurogenesis.

Sex Differences and Estradiol Effects in MAPK and Akt Cell Signaling across Subregions of the Hippocampus.

INTRODUCTION: Rapid effects of estrogens within the hippocampus of rodents are dependent upon cell-signaling cascades, and activation of these cascades by estrogens varies by sex. Whether these pathways are rapidly activated within the dentate gyrus (DG) and CA1 by estrogens across sex and the anatomical longitudinal axis has been overlooked. METHODS: Gonadally intact female and male rats were given either vehicle or physiological systemic low (1.1 µg/kg) or high (37.3 µg/kg) doses of 17ß-estradiol 30 min prior to tissue collection. To control for the effects of circulating estrogens, an additional group of female rats was ovariectomized (OVX) and administered 17ß-estradiol. Brains were extracted, and tissue punches of the CA1 and DG were taken along the longitudinal hippocampal axis (dorsal and ventral) and analyzed for key mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) cascade phosphoproteins. RESULTS: Intact females had higher Akt pathway phosphoproteins (pAkt, pGSK-3ß, and pp70S6K) than males in the DG (dorsal and ventral) and lower pERK1/2 in the dorsal DG. Most effects of 17ß-estradiol on cell signaling occurred in OVX animals. In OVX animals, 17ß-estradiol increased cell signaling of MAPK and Akt phosphoproteins (pERK1/2, pJNK, pAkt, and pGSK-3ß) in the CA1 and pERK1/2 and pJNK DG. DISCUSSION/CONCLUSIONS: Systemic 17ß-estradiol treatment rapidly alters phosphoprotein levels in the hippocampus, dependent on reproductive status, and intact females have greater expression of Akt phosphoproteins than that in intact males in the DG. These findings shed light on underlying mechanisms of sex differences in hippocampal function and response to interventions that affect MAPK or Akt signaling.

Mechanistic Insights in NeuroD Potentiation of Mineralocorticoid Receptor Signaling.

Mineralocorticoid receptor (MR)-mediated signaling in the brain has been suggested as a protective factor in the development of psychopathology, in particular mood disorders. We recently identified genomic loci at which either MR or the closely related glucocorticoid receptor (GR) binds selectively, and found members of the NeuroD transcription factor family to be specifically associated with MR-bound DNA in the rat hippocampus. We show here using forebrain-specific MR knockout mice that GR binding to MR/GR joint target loci is not affected in any major way in the absence of MR. Neurod2 binding was also independent of MR binding. Moreover, functional comparison with MyoD family members indicates that it is the chromatin remodeling aspect of NeuroD, rather than its direct stimulation of transcription, that is responsible for potentiation of MR-mediated transcription. These findings suggest that NeuroD acts in a permissive way to enhance MR-mediated transcription, and they argue against competition for DNA binding as a mechanism of MR- over GR-specific binding.

Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.

Astrocytes are active partners in neural information processing [1, 2]. However, the roles of astrocytes in regulating behavior remain unclear [3, 4]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [5-8], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior. Similarly, excision of the short-period CK1ε tau mutation specifically from SCN astrocytes resulted in lengthened rhythms in the SCN and behavior. These results indicate that astrocytes within the SCN communicate to neurons to determine circadian rhythms in physiology and in rest activity.