Serotonin Pretreatment Abolishes Sex-specific NMDA-induced Seizure Behavior in Developing Rats.

Neuronal excitability and susceptibility to excitotoxic damage can be sex-specific, with neurons from males usually being more 'easily excitable' compared to neurons from females, especially during development. Increased excitability at an individual neuronal level can lead to the formation of hyperexcitable neuronal networks, which, consequently can make the brain more seizure prone. Both animal and clinical data suggest that males experience more frequent and severe seizures than do females.

Early experience alters developmental trajectory of central oxytocin systems involved in hypothalamic-pituitary-adrenal axis regulation in Long-Evans rats.

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored.

Age-dependent sexual dimorphism in hippocampal cornu ammonis-1 perineuronal net expression in rats.

Introduction: Perineuronal nets (PNNs) are extracellular matrices that encompass parvalbumin-expressing parvalbumin positive (PVALB+) fast-spiking inhibitory interneurons where they protect and stabilize afferent synapses. Recent observations that gonadal hormones influence PVALB+ neuron development suggest that PNN regulation may be sexually dimorphic. Sex differences in PNN abundance and complexity have been reported in sexually dimorphic nuclei in zebra finch brains; however, corresponding differences in mammalian brains have not been investigated.

Serotonin receptor regulation as a potential mechanism for sexually dimorphic oxytocin dysregulation in a model of Autism.

Perinatal administration of serotonin (5HT) agonist 5-methoxytryptamine (5MT) induces developmental hyperserotonemia (DHS; elevated blood serotonin) and produces behavioral and neurochemical changes in rats relevant to Autism Spectrum Disorder (ASD), such as oxytocin dysregulation. Disruption of the oxytocin system may underlie many of the social deficits present in ASD individuals, thus we investigated the mechanism(s) underlying DHS-induced oxytocin dysregulation. The most parsimonious mechanism of 5HT action would be alteration of 5HT receptors on oxytocin cells; 5HT is known to influence cell survival as well as influence oxytocin release via 5HT and 5HT receptors, which co-localize in oxytocin-expressing (OXT+) cells in the paraventricular nucleus (PVN) of the hypothalamus.

Gonadal hormone modulation of intracellular calcium as a mechanism of neuroprotection.

Hormones have wide-ranging effects throughout the nervous system, including the ability interact with and modulate many aspects of intracellular calcium regulation and calcium signaling. Indeed, these interactions specifically may help to explain the often opposing or paradoxical effects of hormones, such as their ability to both promote and prevent neuronal cell death during development, as well as reduce or exacerbate damage following an insult or injury in adulthood. Here, we review the basic mechanisms underlying intracellular calcium regulation-perhaps the most dynamic and flexible of all signaling molecules-and discuss how gonadal hormones might manipulate these mechanisms to coordinate diverse cellular responses and achieve disparate outcomes.

Serotonin promotes feminization of the sexually dimorphic nucleus of the preoptic area, but not the calbindin cell group.

Testosterone and its metabolites masculinize the brain during a critical perinatal window, including the relative volume of sexually dimorphic brain areas such as the sexually dimorphic nucleus of the preoptic area (SDN), which is larger in males than females. Serotonin (5HT) may mediate this hormone action, since 5HT given during the second week of life decreases (i.e.

Effects of developmental hyperserotonemia on juvenile play behavior, oxytocin and serotonin receptor expression in the hypothalamus are age and sex dependent.

There is a striking sex difference in the diagnosis of Autism Spectrum Disorder (ASD), such that males are diagnosed more often than females, usually in early childhood. Given that recent research has implicated elevated blood serotonin (hyperserotonemia) in perinatal development as a potential factor in the pathogenesis of ASD, we sought to evaluate the effects of developmental hyperserotonemia on social behavior and relevant brain morphology in juvenile males and females. Administration of 5-methoxytryptamine (5-MT) both pre- and postnatally was found to disrupt normal social play behavior in juveniles.

Methamphetamine facilitates female sexual behavior and enhances neuronal activation in the medial amygdala and ventromedial nucleus of the hypothalamus.

Methamphetamine (MA) abuse has reached epidemic proportions in the United States. Users of MA report dramatic increases in sexual drive that have been associated with increased engagement in risky sexual behavior leading to higher rates of sexually transmitted diseases and unplanned pregnancies. The ability of MA to enhance sexual drive in females is enigmatic since related psychostimulants like amphetamine and cocaine appear not to affect sexual drive in women, and in rodents models, amphetamine has been reported to be inhibitory to female sexual behavior.

Masculinization induced by neonatal exposure to PGE(2) or estradiol alters c-fos induction by estrous odors in adult rats.

Processing of relevant olfactory and pheromonal cues has long been known as an important process necessary for social and sexual behavior in rodents. Several nuclei that receive input from the vomeronasal projection pathway are involved in sexual behavior and show changes in immediate early gene expression after stimulation with a variety of sex-related stimuli. The nuclei in this pathway are sexually dimorphic due to the early patterning events induced by estradiol derived from testicular androgens, which developmentally defeminize and masculinize the brain and adult sexual behavior.

GABAergic mechanism of propofol toxicity in immature neurons.

Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, is excitatory on immature neurons via its action at the GABAA receptor, due to a reversed transmembrane chloride gradient. GABAA receptor activation in immature neurons is sufficient to open L-type voltage-gated calcium channels.

Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism?

The hippocampus is a key brain region regulating complex cognitive and emotional responses, and is implicated in the etiology of depressive and anxiety disorders, many of which exhibit some degree of sex difference. The male rat hippocampus is consistently reported to be slightly but significantly larger than the female. The majority of studies on the development of volumetric sex differences have focused on the effects of estradiol (E2), with relatively few focusing on androgens.

Focal adhesion kinase and paxillin: novel regulators of brain sexual differentiation?

Steroid-mediated sexual differentiation of the brain is a developmental process that permanently organizes the brain into a male or female phenotype. Previous studies in the rodent have examined the steroid-mediated mechanisms of male brain development. In an effort to identify molecules involved in female brain development, a high-throughput proteomics approach called PowerBlot was used to identify signaling proteins differentially regulated in the neonatal male and female rat hypothalamus during the critical period for brain sexual differentiation.

Neuroprotection by ovarian hormones in animal models of neurological disease.

Ovarian hormones can protect against brain injury, neurodegeneration, and cognitive decline. Most attention has focused on estrogens and accumulating data demonstrate that estrogen seems to specifically protect cortical and hippocampal neurons from ischemic injury and from damage due to severe seizures. Although multiple studies demonstrate protection by estrogen, in only a few instances is the issue of how the steroid confers protection known.

Overexpression of bcl-2 reduces sex differences in neuron number in the brain and spinal cord.

Several sex differences in the nervous system depend on differential cell death during development in males and females. The anti-apoptotic protein, Bcl-2, promotes the survival of many types of neurons during development and in response to injury. To determine whether Bcl-2 might similarly control cell death in sexually dimorphic regions, we compared neuron number in wild-type mice and transgenic mice overexpressing Bcl-2 under the control of a neuron-specific promoter.

Testosterone regulates BCL-2 immunoreactivity in a sexually dimorphic motor pool of adult rats.

Bcl-2 and Bax immunoreactivity were examined in the spinal nucleus of the bulbocavernosus (SNB), an androgen-sensitive motor pool of adult rats. Castration reduced Bcl-2 immunoreactivity and testosterone treatment of castrates prevented this decline. Hormone manipulations did not affect Bcl-2 or Bax staining in the retrodorsolateral nucleus (RDLN), a relatively androgen-insensitive nucleus at the same spinal level.