Effects of testosterone on female rat sexual behavior

Estrogen and progesterone are ovarian steroid hormones involved in the initiation and maintenance of female sexual behaviors. Recent research suggests that testosterone (T) is also important in sexual behavior, particularly in the restoration of libido in surgically and naturally menopausal women when administered with estrogen (E). The effect of T on the female sexual behavior of aged intact, and young ovariectomized rats has been poorly described in the current literature, despite varying reports offacilitative and inhibitory effects. The goal of the present thesis was to examine the actions of E, T, or their combination, in the restoration of sexual activity at a time when ovarian function is altered either through aging or surgical removal of the ovaries. The effects of both acute and chronic administration of these hormones on sexual behavior were observed. The results of these experiments suggest that the combined action of E with T may facilitate sexual behaviors in young ovariectomized female rats, to levels equivalent to optimal priming with E and progesterone. When varying hormone regimens were administered to aged intact animals, by phasic subcutaneous injections every four days, there was no effect on their sexual behavior acutely, whereas chronic T and E+T resulted in an attenuation of sexual behaviors. When a continuous release of T was administered to aged intact female rat by subcutaneous capsule, sexual behaviors were initially facilitated, but the effect dissipated over time. The mechanism underlying this process is suggested

Estradiol Sensitization of Sexual Behaviors in the Ovariectomized Rat: Mechanisms and Applications

Estradiol sensitization refers to a phenomenon whereby each subsequent injection of estradiol benzoate (EB), when administered to the ovariectomized (OVX) rat to induce sexual behavior, potentiates the occurrence of those behaviors. The goals of the current thesis were to characterize the pattern of estradiol sensitization by varying the EB dose and injection interval, to examine some behavioral, hormonal, and neural factors involved in its induction and maintenance, and to apply it as a diagnostic tool in models that have been shown in the literature to produce sexual inhibition. It was first determined that estradiol sensitization is robustly induced by 10μg EB administered SC every 4 days, and that the effect is further potentiated if EB is administered in the absence of the opportunity to copulate. Furthermore, although adrenal progesterone (P) did not play a role, chronic administration of systemic injections of the P receptor antagonist RU486 revealed that P receptors are important in the maintenance of the sensitization. The next set of experiments determined that vaginocervical stimulation (VCS) received on repeated tests attenuates the sensitization of appetitive sexual behaviors (hops, darts, solicitations), and that inhibitory mechanisms related to estrous termination may be involved, since the attenuation was mimicked by repeated infusions of the glutamate receptor agonist AMPA to the ventrolateral division of the ventromedial hypothalamus in place of copulation. Moreover, the onset of estrous termination was accelerated in estradiol-sensitized animals that were not given the opportunity to copulate. This suggests that estradiol sensitizes mechanisms of sexual excitation and inhibition. The final experimental chapter determined that prenatally androgenized females are not permanently desensitized to the activational effects of EB, since repeated hormone treatments in combination with sexual experience generally restored sexual behaviors and those females also displayed estradiol sensitization. Finally, the inhibitory effect of corncob bedding, as reported recently in the literature, did not prevent estradiol sensitization. In conclusion, the extent of estradiol sensitization, and the duration of behavioral estrus in estradiol-sensitized animals, interacts with sexual experience, particularly VCS. The data presented herein have implications for all research areas investigating the role of estradiol on physiology and behavior

Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice

Potassium (K+) channels shape the response properties of neurons. Although enormous progress has been made to characterize K+ channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and single molecule fluorescent in situ hybridization, we localized expression of transcripts encoding the sodium-activated potassium channels K(Na)1.1(SLO2.2/Slack) and K(Na)1.2 (SLO2.1/Slick) to the primary auditory neurons (spiral ganglion neurons, SGNs). To examine the contribution of these channels to function of the SGNs in vivo, we measured auditory brainstem responses in K(Na)1.1/1.2 double knockout (DKO) mice. Although auditory brainstem response (wave I) thresholds were not altered, the amplitudes of suprathreshold responses were reduced in DKO mice. This reduction in amplitude occurred despite normal numbers and molecular architecture of the SGNs and their synapses with the inner hair cells. Patch clamp electrophysiology of SGNs isolated from DKO mice displayed altered membrane properties, including reduced action potential thresholds and amplitudes. These findings show that K(Na)1 channel activity is essential for normal cochlear function and suggest that early forms of hearing loss may result from physiological changes in the activity of the primary auditory neurons

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys.Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS.Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors.Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors.Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience

Spiral Ganglion Degeneration and Hearing Loss as a Consequence of Satellite Cell Death in Saposin B-Deficient Mice

Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B’s role in hearing and balance, a Sap B-deficient (B-/-) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen at postnatal month 6 and progressed thereafter for frequency-specific stimuli, whereas click responses became abnormal from postnatal month 13 onward. The progressive hearing loss correlated with the accumulation of inclusion bodies in the satellite cells and their subsequent degeneration. Outer hair cell numbers and efferent function measures (distortion product otoacoustic emissions and contralateral suppression) were normal in the B-/- mice throughout this period. Alcian blue staining of SGs demonstrated that these inclusion bodies corresponded to sulfatide accumulation. In contrast, changes in the vestibular system were much milder, but caused severe physiologic deficits. These results demonstrate that loss of Sap B function leads to progressive sulfatide accumulation in satellite cells surrounding the SG neurons, leading to satellite cell degeneration and subsequent SG degeneration with a resultant loss of hearing. Relative sparing of the efferent auditory and vestibular neurons suggests that alternate glycosphingolipid metabolic pathways predominate in these other systems

Longitudinal associations between paternal mental health and child behavior and cognition in middle childhood

IntroductionPaternal mental health has been associated with adverse consequences on offspring psychosocial development, and family environmental factors may partly explain those associations. To clarify this, we need comprehensive prospective studies, particularly in middle-childhood when the child enters school and is expected to make use of behavioral and cognitive skills as part of their interactions and learning.MethodUsing data from a sub-sample of the prospective 3D birth cohort study comprised of mother-father-child triads, and a follow-up of the parents and the children at 6–8 years of age (n = 61; 36 boys, 25 girls), we examined whether paternal anxious and depressive symptoms measured during the pregnancy period (i.e., prenatally) or concurrently when the child was assessed at 6–8 years old were associated with children's cognition/behavior.ResultsIn contrast to our hypotheses, we found that greater prenatal paternal depressive symptoms predicted fewer child behavioral difficulties; and that greater concurrent childhood paternal depression or anxiety symptoms were associated with higher child full-scale IQ, controlling for the equivalent maternal mental health assessment and parental education. Father parenting perception did not mediate these associations, nor were they moderated by maternal mental health at the concurrent assessment, or paternal ratings of marital relationship quality.DiscussionThese findings suggest that higher symptoms of paternal mental health symptoms are associated with fewer child behavioral difficulties and higher cognitive performance in middle childhood. Potential clinical implications and future research directions are discussed

Tricellulin deficiency affects tight junction architecture and cochlear hair cells

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear potential and paracellular permeability of a biotin-based tracer in the stria vascularis were unaltered. Freeze-fracture electron microscopy revealed disruption of the strands of intramembrane particles connecting bicellular and tricellular junctions in the inner ear epithelia of tricellulin-deficient mice. These ultrastructural changes may selectively affect the paracellular permeability of ions or small molecules, resulting in a toxic microenvironment for cochlear hair cells. Consistent with this hypothesis, hair cell loss was rescued in tricellulin-deficient mice when generation of normal endolymph was inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally, comprehensive phenotypic screening showed a broader pathological phenotype in the mutant mice, which highlights the non-redundant roles played by tricellulin

Imaging the pituitary in psychopathologies: a review of in vivo magnetic resonance imaging studies

The pituitary gland (PG) is a key component of the essential endocrine systems in humans and animals, including the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-gonadal, and hypothalamic-pituitary-thyroid axes. Structural changes in the PG are observed in a number of psychiatric disorders. Psychiatric disorders are typically characterized by subtle, time-dependent anatomical changes in the brain, and their study necessitates highly powered, longitudinal investigations. Structural magnetic resonance imaging (MRI) is a non-invasive technology that is ideally suited to detect changes in anatomical structures over time. In this paper, we will review the main findings on pituitary function and structure in the context of healthy development and of psychiatric disorders, with particular emphasis on MRI studies. The latter have not always succeeded in providing a clear theoretical framework of mental disorders, which may be explained by low resolution and differences in preprocessing methods, imprecise segmentation rules that do not account for the anatomical and functional specificity of the anterior and posterior lobes of the PG, and inadequate categorization of clinical subjects. We review those limitations and propose solutions for future research.publishe

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors : Sex Specific Effects in Project Ice Storm

The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys. Aims. To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed to varying levels of disaster-related PNMS. Methods. Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers’ disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist. Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors. Results. In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors. Conclusion. These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother’s stress experience.publishe

Developmental variation in testosterone: Cortisol ratio alters cortical- and amygdala-based cognitive processes

Testosterone (T) and cortisol (C) are the end products of neuroendocrine axes that interact with the process of shaping brain structure and function. Relative levels of T:C (TC ratio) may alter prefrontal-amygdala functional connectivity in adulthood. What remains unclear is whether TC-related effects are rooted to childhood and adolescence. We used a healthy cohort of 4-22-year-olds to test for associations between TC ratios, brain structure (amygdala volume, cortical thickness (CTh), and their coordinated growth), as well as cognitive and behavioral development. We found greater TC ratios to be associated with the growth of specific brain structures: 1) parietal CTh; 2) covariance of the amygdala with CTh in visual and somatosensory areas. These brain parameters were in turn associated with lower verbal/executive function and higher spatial working memory. In sum, individual TC profiles may confer a particular brain phenotype and set of cognitive strengths and vulnerabilities, prior to adulthood