Female Amygdala Research Articles

Differential Effect of Prenatal Stress on the Expression of Cortiocotrophin-Releasing Hormone and its Receptors in the Hypothalamus and Amygdala in Male and Female Rats

The present study examined the effect of prenatal stress in rats from days 13-20 of gestation on anxiogenic behaviour in the elevated plus maze (EPM) together with changes in the gene expression of corticotrophin-releasing hormone (CRH), its receptors, CRHR1 and CRHR2, as well as CRH binding protein (CRH-BP) in the paraventricular nucleus (PVN) and amygdala of their male and female offspring. Both prenatally-stressed (PS) males and females showed heightened anxiety in the EPM. Prenatal stress did not alter the gene expression of CRH or its receptors in the male PVN, although it decreased CRH-BP mRNA, which could augment the activity of free CRH. In the PVN of PS females, there was an increase in the expression of CRH, coupled with a decrease in that of CRHR2 and CRH-BP. These changes are compatible with the greater activation of the hypothalamic pituitary adrenal axis to stress in females. Anxiogenic behaviour of PS rats was associated with a reduction of CRHR2 mRNA and of CRH-BP mRNA in the amygdala of males and an increase in CRH mRNA and decrease in CRHR2 mRNA in females. Two hours after acute stress of exposure to the elevated plus maze in which heightened anxiety was manifested, increases were seen only in the amygdala of females in CRH and CRHR1 signalling, whereas CRHR2 mRNA was reduced in both sexes. The data show that both prenatal stress and acute stress in adulthood have a differential sex-dependent effect on the expression of CRH its receptors and binding protein in the PVN and amygdala of rats.

Aromatase mRNA in the Brain of Adult Green Anole Lizards: Effects of Sex and Season

Neural testosterone metabolism, particularly the synthesis of oestradiol (E(2)) via the aromatase enzyme, is important for sexual behaviours in many vertebrates. In green anole lizards, E(2) metabolised from testosterone facilitates female receptivity and increases sexual motivation in males. Testosterone treatment increases aromatase activity in the whole brain homogenates of gonadectomised male, but not female, anoles, which is an effect limited to the breeding season (BS). To investigate the potential for local effects of this enzyme in reproductive behaviour, we used in situ hybridisation for aromatase mRNA to examine expression during the BS and nonbreeding season (NBS) in areas of the brain that control male sexual behaviours [preoptic area (POA) and amygdala (AMY)], as well as one regulating female reproductive behaviours ventromedial hypothalamus (VMH). Males had a greater total number of aromatase-expressing cells in the POA than females, and the density of aromatase-expressing cells (number per unit volume) was greater in the VMH and AMY of females. This density was also higher during the BS than NBS in the POA. Expression of aromatase in the AMY appeared to be lateralised because trends were detected for the left side to have more total cells and more cells per unit volume than the right. These results suggest that, similar to other vertebrates, regional aromatisation of testosterone may be important for the control of sex-specific reproductive behaviours.

Sex and regional differences in estradiol content in the prefrontal cortex, amygdala and hippocampus of adult male and female rats

In general, the behavioral and neural effects of estradiol administration to males and females differ. While much attention has been paid to the potential structural, cellular and sub-cellular mechanisms that may underlie such differences, as of yet there has been no examination of whether the differences observed may be related to differential uptake or storage of estradiol within the brain itself. We administered estradiol benzoate to gonadectomized male and female rats, and compared the concentration of estradiol in serum and brain tissue found in these rats to those of gonadectomized, oil-treated rats and intact rats of both sexes. Long-term gonadectomy (3 weeks) reduced estradiol concentration in the male and female hippocampus, but not in the male or female amygdala or in the female prefrontal cortex. Furthermore, exogenous treatment with estradiol increased estradiol content to levels above intact animals in the amygdala, prefrontal cortex and the male hippocampus. Levels of estradiol were undetectable in the prefrontal cortex of intact males, but were detectable in all other brain regions of intact rats. Here we demonstrate (1) that serum concentrations of estradiol are not necessarily reflective of brain tissue concentrations, (2) that within the brain, there are regional differences in the effects of gonadectomy and estradiol administration, and (3) that there is less evidence for local production of estradiol in males than females, particularly in the prefrontal cortex and perhaps the hippocampus. Thus there are regional differences in estradiol concentration in the prefrontal cortex, amygdala and hippocampus that are influenced by sex and hormone status.

Morphology and estrogen receptor α mRNA expression in the developing green anole forebrain

Sex differences in forebrain morphology arise during development and are often linked to hormonal changes. These dimorphisms frequently occur in regions related to reproductive behaviors. Little is known about the normal ontogeny of reproductive nuclei in the green anole lizard, including whether steroid hormones influence their development. To address this issue, brain region volume, cell density, soma size, and estrogen receptor alpha (ERalpha) mRNA expression were characterized in the preoptic area (POA), ventromedial amygdala (AMY), and ventromedial hypothalamus (VMH) of late embryonic and early post-hatchling anoles. In adulthood, the POA and AMY are associated with male-specific reproductive behaviors and the VMH is implicated in female receptivity. Although soma size decreased in all brain regions with age, brain region volume diminished only in the POA, with a transient sex difference appearing before hatching. Cell density increased with age only in the female AMY. ERalpha mRNA expression was up to four times greater in the developing VMH than POA and AMY, peaking in the VMH around the day of hatching. These results are consistent with the idea that estradiol may influence differentiation of the VMH in particular. However, other factors are likely important to the development of these three brain regions, some of which exert their effects at later developmental stages.

Reduced ventral anterior cingulate and amygdala volumes in medication-naïve females with major depressive disorder: A voxel-based morphometric magnetic resonance imaging study

High resolution magnetic resonance imaging and voxel-based morphometry were used to compare regional gray matter volumes between 14 medication-naïve female participants with a first episode of major depressive disorder (MDD) and 13 female healthy comparison participants (HC). Volumes of bilateral ventral anterior cingulate cortex (vACC) and right amygdala were significantly smaller in the MDD group than in the HC group. These results suggest that volume reductions in vACC and amygdala in females with MDD are present at illness onset.

Wnt Pathway Anomalies in Developing Amygdalae of Turner Syndrome-like Mice

Certain neurobehavioral deficiencies associated with Turner Syndrome have been attributed to brain volumetric abnormalities, particularly of the amygdala. Haplo-insufficiency of a non-dosage compensated gene or genes on the X chromosome has been hypothesized to be the cause of the neuroanatomical defect. We examined gene expression levels of 6,628 genes in developing amygdalae of late-stage embryos of a mouse model for Turner Syndrome. In total, 161 genes show significant differences in expression level between TS and normal female amygdala. In silico pathway analysis of both X-linked and autosomal mis-regulated genes suggests that modulation of Wnt signaling is a critical factor in the normal growth and development of the amygdala.

Amygdala function in adolescents with congenital adrenal hyperplasia: A model for the study of early steroid abnormalities

Early disruption of steroids affects the development of mammalian neural circuits underlying affective processes. In humans, patients with classic congenital adrenal hyperplasia (CAH) can serve as a natural model to study early hormonal alterations on functional brain development. CAH is characterized by congenital glucocorticoid insufficiency, leading to altered hypothalamic–pituitary–adrenal (HPA) function, and hyperandrogenism. Using fMRI, we compared fourteen adolescents with CAH to 14 healthy controls on amygdala response to a face viewing task. In response to negative facial emotions, CAH females activated the amygdala significantly more than healthy females, whereas CAH males did not differ from control males. Furthermore, females with CAH showed a similar pattern of amygdala activation to control males, suggesting virilized amygdala function in females with CAH. These findings suggest a prominent effect of early hyperandrogenism on the development and function of the amygdala in females with CAH, whereas no effects were detected in males with CAH. This study provides data that can be further tested in a model of the neurobiological mechanisms underlying early androgen organizational effects on amygdala function.

Sex-related differences in amygdala functional connectivity during resting conditions

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.

Medullary noradrenergic neurons release norepinephrine in the medial amygdala in females in response to mating stimulation sufficient for pseudopregnancy

In the female rat, stimuli from the uterine cervix and vagina are carried to the brain areas involved in the mating-induced pseudopregnancy (PSP) response via the ventral noradrenergic bundle. Noradrenergic neurons projecting through this tract synapse in many forebrain areas including the amygdala, and neurons in the posterodorsal medial amygdala (MePD) are activated following mating. The goal of this experiment was to investigate whether norepinephrine (NE) is released into the MePD after mating using microdialysis and to determine the origin of this release. Ovariectomized estrogen- and progesterone-treated rats were implanted unilaterally with guide cannulae aimed at the MePD. Females were placed with males until they received 15 intromissions (15I), 5 intromissions (5I) or 15 mounts-without-intromission (MO). Dialysate samples collected every 20 min for 2 h before to 3 h after mating were analyzed for NE using HPLC with electrochemical detection. A significant increase in mean NE release in the MePD was seen at 80 min after mating onset in females receiving 15I, and no increase was seen in animals receiving 5I or MO. The time of peak NE release varied in 15I animals from 60 to 160 min after mating. Mean baseline levels of NE did not differ between groups. The retrograde tracer FluoroGold (FG), administered through the probe after cessation of dialysis sampling, was observed within identified noradrenergic cells primarily within the A1 and A2 cell groups. Infusion of anti-dopamine-β-hydroxylase-saporin (DBH-SAP) into the MePD lesioned noradrenergic neurons located in the A1 and A2 cell groups. Because high levels of NE release occurred in the MePD only after the females received a number of intromissions sufficient to induce PSP, these results suggest that NE release within the MePD may be important for the establishment of PSP.

FOS expression in grafted gonadotropin-releasing hormone neurons in hypogonadal mouse: Mating and steroid induction

We used FOS expression, widely accepted as a marker for neuronal activation, to evaluate physiologically induced activation of gonadotropin-releasing hormone (GnRH) neurons within intraventricular preoptic area grafts in hypogonadal (hpg) female mice. Hpg mice lack endogenous GnRH due to a mutated gene, but can respond to grafted GnRH neurons with reproductive development. The purpose of this study was to determine the degree to which the host brain regulates grafted GnRH neurons. FOS expression in grafted GnRH neurons was induced in progesterone-primed female mice paired with sexually active males. The degree of sexual activity did not affect the outcome, with 40.9 +/- 12.2% of the grafted GnRH cells expressing FOS when male partners performed intromissions, and 47.5 +/- 10.2% when they also ejaculated. There was little or no FOS expression in the grafts of unprimed hpg mice paired with sexually active males, in unpaired mice primed with progesterone or sequential estradiol benzoate and progesterone, or in controls. The pattern of FOS expression in the brains of the female hpg mice engaged in mating behavior was similar to that reported in other species, with moderate to high expression in the medial preoptic area, ventromedial nucleus, and medial amygdala in females paired with males that ejaculated. The present results support the hypothesis that host-derived activation of grafted GnRH neurons underlies aspects of reproductive responses seen in hpg mice with grafts, and further, that at least a portion of the host-graft connectivity is steroid sensitive.

C-Fos expression in female hamster brain following sexual and aggressive behaviors

The goal of these experiments was to use c-Fos immunocytochemistry to determine areas of the female hamster brain that are active during lordosis and aggression. Ovariectomized hamsters were given (i) estradiol and progesterone, plus a lordosis test, (ii) estradiol and progesterone, but no lordosis test, (iii) oil, plus an aggressive behavior test, or (iv) oil, but no behavior test. Results showed that following lordosis, there was increased c-Fos expression in the medial bed nucleus of the stria terminalis, medial accumbens, medial preoptic nucleus, paraventricular nucleus and medial amygdala. Following a single aggression test, c-Fos was significantly increased only within the medial amygdala. There was no effect of lordosis or aggression on c-Fos expression within the lateral or central ventromedial hypothalamus, suprachiasmatic nucleus or dorsal midbrain central gray. In a second experiment, ovariectomized female hamsters were given (i) repeated aggressive experience, (ii) a single aggression test or (iii) no aggression test. Because some females were not aggressive towards males, they became a separate group post hoc. The number of cells expressing c-Fos was higher in the medial preoptic nucleus and medial amygdala of females given a single aggressive test and in non-aggressive females vs control females. Females given prior aggressive experience showed higher c-Fos expression only in the medial preoptic nucleus. These results demonstrate that increased neural activation in several forebrain nuclei is seen after sexual or aggressive behaviors in female hamsters. However, because the pattern of c-Fos staining in the non-aggressive females was similar to the pattern in aggressive females, this questions previous conclusions regarding the behavioral specificity of these effects and suggests instead that such activation is common to social interactions in general.

Gonadal steroid modulation of vasotocin concentrations in the bullfrog brain.

Concentrations of the neuropeptide arginine vasotocin (AVT) are sexually dimorphic in some regions of the bullfrog brain. Since these differences in AVT content may be due to sexual differences in plasma steroid concentrations, we performed a gonadectomy-steroid replacement experiment (30-day treatment) to assess the effects of specific steroids on AVT concentrations (determined by RIA) in adult male and female bullfrogs (Rana catesbeiana). These treatments had significant effects in six brain areas. Gonad removal decreased AVT concentrations in the amygdala pars lateralis, septal nucleus and habenula of both sexes. Gonadectomy decreased AVT content in optic tectum, torus semicircularis and pretrigeminal nucleus of males only. Dihydrotestosterone treatment resulted in AVT concentrations at or above sham levels in all six areas, whether or not gonadectomy decreased content. Estradiol fully restored AVT concentrations only in the septal nucleus and habenula (of both sexes) and in the amygdala of females. Estradiol partially restored AVT levels in the amygdala of males. These results indicate that the gonads maintain AVT concentrations in several brain areas and that steroids can modulate levels of AVT in bullfrog brain. Effects of each steroid vary depending upon the region and sex of the frog. AVT cells are present in three of these regions--the amygdala pars lateralis, septal nucleus and pretrigeminal nucleus. Steroids may be directly affecting AVT synthesis in these cells and these populations may be the source of AVT fibers in the other steroid-sensitive areas.

An androgen receptor in rat brain and pituitary

Dihydrotestosterone (DHT) binding was measured in cytosols from brain regions and pituitary of adult female rats and, with the addition of ventral prostate, in adult male rats. Two types of binding were distinguished: one, saturable at concentration of DHT⩾ 5 × 10 −9 M and an unsaturable component. In intact males saturable (limited capacity) binding was detected only in ventral prostate cytosol; 3 days after orchidectomy the saturable binding sites increase 3-fold in prostate and in pituitary, hypothalamus, amygdala and cortex to detectable levels in approximately the same abundance as in females. There were significant differences in the affinities of the limited capacity binding reactions in cytosols of different tissues though all were in the order of magnitude, 10 −9 M DHT. The affinity in pituitary cytosol was lower than in brain regions with the single exception of female amygdala in which the affinity was significantly lower than in cytosol of the same region from 3-day castrate males. The specificity of the limited capacity binding was investigated by competition between [ 3H]DHT and unlabelled steroids; the most effective competitors were potent androgen agonists and antagonists.