Does having a twin-brother make for a bigger brain?

Objective: Brain volume of boys is larger than that of girls by ∼10%. Prenatal exposure to testosterone has been suggested in the masculinization of the brain. For example, in litter-bearing mammals intrauterine position increases prenatal testosterone exposure through adjacent male fetuses, resulting in masculinization of brain morphology. Design: The influence of intrauterine presence of a male co-twin on masculinization of human brain volume was studied in 9-year old twins. Methods: Magnetic resonance imaging brain scans, current testosterone, and estradiol levels were acquired from four groups of dizygotic (DZ) twins: boys from same-sex twin-pairs (SSM), boys from opposite-sex twin-pairs (OSM), girls from opposite-sex twin-pairs (OSF), and girls from same-sex twin-pairs (SSF; n=119 individuals). Data on total brain, cerebellum, gray and white matter volumes were examined. Results: Irrespective of their own sex, children with a male co-twin as compared to children with a female co-twin had larger total brain (+2.5%) and cerebellum (+5.5%) volumes. SSM, purportedly exposed to the highest prenatal testosterone levels, were found to have the largest volumes, followed by OSM, OSF and SSF children. Birth weight partly explained the effect on brain volumes. Current testosterone and estradiol levels did not account for the volumetric brain differences. However, the effects observed in children did not replicate in adult twins. Conclusions: Our study indicates that sharing the uterus with a DZ twin brother increases total brain volume in 9-year olds. The effect may be transient and limited to a critical period in childhood. © 2009 European Society of Endocrinology

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia

Studies in pasture utilization by the grazing animal

It is shown that information was required on the factors affecting the daily herbage intake of grazing cattle, and methods of estimating herbage intake under grazing conditions are reviewed. A new method which was devised is described by which the herbage dry matter intakes of individual cows in small plots were to be determined from the difference between the yields of herbage before and after grazing periods of 24- hours duration. The yields were to be estimated from herbage samples clipped by hand to ground level. The aim of this method was (a) to eliminate bias, (b) to allow the determination of the errors of the estimates by analysis of variance and (c) to achieve precision by replication of both cows and days. Five grazing experiments are described in which this method was used to estimate the herbage intake of Ayrshire cattle of various body weights and milk yields when grazing swards of various qualities and yields per acre. In the last of these the effects of supplementary feed on herbage intake and milk production are also reported. A sixth experiment is described in which herbage of a similar quality to that provided in the grazing experiments was cut and fed fresh or dried to housed cattle in order to compare their rate of intake with that estimated at pasture. Finally some data on the effects of excrements on pasture utilization are given and an estimate is made of their probable effects at various intensities of stocking. The results are discussed with reference to the results reported by other workers, and it is concluded that the method of intake estimation used here gives a higher degree of precision than most other methods and is relatively free from bias. The present experiments are cori5)ared and it is shown that although the daily dry matter intake of the cattle was in general related to their body weight, there were differences in intake iDetween individual cows which were related to their stage of lactation and milk yield. Their herbage intake increased with increasing yields of herbage per acre but decreased with a heavier rate of stocking per acre. Supplementary feed gave only slight increases in milk yield and depressed the intake of herbage in poor grazing conditions. The dry matter content of the herbage was found to have no influence on the amounts of herbage consumed, but the cows varied their water consumption from day to day so as to maintain an almost constant ratio between dry matter and total water consumption. It is concluded that the effect of herbage yields and of stocking intensity on intake and the low general level of dry matter intake which was found relative to accepted feeding standards may be ascribed to the effects of the grazing system on the quality of herbage consumed. The need is suggested for studies on the optimal stage of growth of pasture herbage required to gain maximal outputs of animal produce per acre

The Environmental Estrogen Bisphenol A Inhibits Estradiol-Induced Hippocampal Synaptogenesis

Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 μg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines

Sexually Dimorphic Effects of Prenatal Stress on Cognition, Hormonal Responses, and Central Neurotransmitters

Exposure to stress during gestation results in physiological and behavioral alterations that persist into adulthood. This study examined the effects of prenatal stress on the postnatal expression of sexually differentiated cognitive, hormonal, and neurochemical profiles in male and female rats. Pregnant dams were subjected to restraint stress three times daily for 45 min during d 14-21 of pregnancy. The offspring of control and prenatally stressed dams were tested for anxiety-related and cognitive behaviors, stress and gonadal steroid hormone levels, as well as monoamines and metabolite levels in selected brain regions. Postnatal testosterone levels (measured at 1 and 5 d) did not differ between controls and prenatally stressed animals. In adulthood, the serum corticosterone response to stress was attenuated in prenatally stressed females, eliminating the sex difference normally observed in this parameter. Prenatally stressed females exhibited higher anxiety levels, evidenced by longer open field entry latencies. Prenatal stress had no effect on object recognition memory, but eliminated the advantage normally seen in the male performance of a spatial memory task. Neurochemical profiles of prenatally stressed females were altered toward the masculine phenotype in the prefrontal cortex, amygdala, and hippocampus. Thus, prenatal stress altered subsequent cognitive, endocrine, and neurochemical responses in a sex-specific manner. These data reinforce the view that prenatal stress affects multiple aspects of brain development, interfering with the expression of normal behavioral, neuroendocrine, and neurochemical sex differences. These data have implications for the effects of prenatal stress on the development of sexually dimorphic endocrine and neurological disorders

The role of grassland sward islets in the distribution of arthropods in cattle pastures

1. It is well documented that cattle reduce their grazing activity in the vicinity of cattle dung, which gives rise to distinct patches, or islets as they have been termed, of longer sward. The influence of such islets on pasture utilisation and agronomic performance has been widely studied, but very little information is available concerning their influence on grassland biodiversity. 2. In this study the abundance and distribution of arthropods in relation to islets was assessed, using suction sampling, at 26 commercial farms and in a replicated pasture management experiment in the south and east of Ireland. 3. Islets were found to cover approximately 24% of pastures and to contain between 40% and 50% of arthropod individuals. 4. Islets consistently contained a higher density of arthropods, even when the difference in mean sward height between islets and more strongly grazed sward was accounted for. The relative concentration of arthropods in islets declined with increasing mean sward height, which may be related to the recovery of well-grazed non-islet sward. Islets appear to act as refugia from sward removal. 5. The potential importance of islets in maintaining arthropod biodiversity within intensively grazed pastures and the wider grass-based farming landscape is discussed, particularly with reference to standard agronomic practices such as sward topping and chain harrowing, which aim to remove the sward heterogeneity created by grazing livestock

Neurosteroid Metabolites of Gonadal Steroid Hormones in Neuroprotection: Implications for Sex Differences in Neurodegenerative Disease

Gonadal steroid hormones are neurotrophic and neuroprotective. These effects are modulated by local metabolism of the hormones within the brain. Such control is necessary to maintain normal function, as several signaling pathways that are activated by gonadal steroid hormones in the brain can also become dysregulated in disease. Metabolites of the gonadal steroid hormones—particularly 3α-hydroxy, 5α-reduced neurosteroids—are synthesized in the brain and can act through different mechanisms from their parent steroids. These metabolites may provide a mechanism for modulating the responses to their precursor hormones, thereby providing a regulatory influence on cellular responses. In addition, there is evidence that the 3α-hydroxy, 5α-reduced neurosteroids are neuroprotective in their own right, and therefore may contribute to the overall protection conferred by their precursors. In this review article, the rapidly growing body of evidence supporting a neuroprotective role for this class of neurosteroids will be considered, including a discussion of potential mechanisms that may be involved. In addition, we explore the hypothesis that differences between males and females in local neurosteroid production may contribute to sex differences in the development of neurodegenerative disease

LUMAN/CREB3 Plays a Dual Role in Stress Responses as a Cofactor of the Glucocorticoid Receptor and a Regulator of Secretion

LUMAN/CREB3, originally identified through its interaction with a cell cycle regulator HCFC1, is a transcription factor involved in the unfolded protein response during endoplasmic reticulum stress. Previously using gene knockout mouse models, we have shown that LUMAN modulates the glucocorticoid (GC) response leading to enhanced glucocorticoid receptor (GR) activity and lower circulating GC levels. Consequently, the stress response is dysregulated, leading to a blunted stress response in the Luman-deficient mice. One question that remained was how LUMAN deficiency affected the stress response at the cellular level leading to the changes in the physiological stress response. Here, we found that LUMAN interacts with GR through a putative nuclear receptor box site and can activate GR in the absence of a ligand. Further investigation showed that, when activated, LUMAN binds to the glucocorticoid response element (GRE), increasing the activity of GR exponentially compared to GR-ligand binding alone. On the other hand, we also found that in the absence of LUMAN, cells were more sensitive to cellular stress, exhibiting decreased secretory capacity. Hence our current data suggest that LUMAN may function both as a transcriptional cofactor of GR and a hormone secretion regulator, and through this, plays a role in stress sensitivity and reactivity to stress