Paloma Collado

The development of sex differences in the locus coeruleus of the rat

Development of sex differences in the locus coeruleus (LC) is investigated. The LC is a sexually dimorphic structure in which the female manifests a larger volume and greater number of neurons than do males. Male and female Wistar rats were sacrificed on prenatal days (E) 16 and 20 and postnatally (P) on days 1, 3, 7, 15, 35, 45, 60, and 90. Male and female rats show a continuous increase in the number of neurons after birth that stops in the males by P45 and in females by P60. These findings point out the existence of different patterns of development in male and female rats and may suggest that sex differences could be established because of the existence of a differential period of neurogenesis in both sexes in the postpubertal period.

Sexual dimorphism in the bed nucleus of the accessory olfactory tract in the rat

This work investigates the existence of sex differences in the volume and number of neurons and glial cells in the bed nucleus of the accessory olfactory tract (BAOT). Males showed larger volume and number of cells than female rats. Early postnatal (day 1 after birth) orchidectomy in males, and androgenization in females, reversed these differences. No sex differences were found in BAOT glial cells. The sexual dimorphism found in the neuron/glial cell ratio reflects sex differences in neuron number. The existence of sexual dimorphism in the BAOT supports our earlier hypothesis which states that the vomeronasal system (VNS) is sexually dimorphic.

Bilateral lesions of the bed nucleus of the accessory olfactory tract facilitate maternal behavior in virgin female rats

In this study the effects of electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) on the induction of maternal behavior in virgin female Wistar rats was investigated. Results demonstrate a functional role of the BOAT in the neural control of maternal behavior in virgin female rats since bilaterally BOAT lesioned (BL) animals showed significantly shorter sensitization latencies (BL = 6 days) than sham lesioned (SH = 12 days) and intact control (C = 12 days) female rats. At the same time, statistically significant differences were observed in retrieval latency between BL (5.5 days) and C (10 days) groups, but not in the SH group (8 days). In physical contact frequency, the BL group reached higher scores than SH or C group. However, bilateral BAOT lesions failed to affect other maternal patterns such as nest building quality. Thus these results indicate that the BOAT, a vomeronasal system structure, is involved in the control of maternal behavior and that BL electrolytic lesions facilitate the onset of this behavior in virgin female Wistar rats.

The role of the androgen receptor in CNS masculinization

The medial posterior region of the bed nucleus of the stria terminalis (BSTMP) and the locus coeruleus (LC) show opposite patterns of sexual dimorphism. The BSTMP in males is greater in volume and number of neurons than in females (male > female) while in the LC, the opposite is true (female > male). To investigate the possible role of the androgen receptor (AR) in the masculinization of these two structures, males with the testicular feminization mutation (Tfm) were compared to their control littermate males. No differences were seen in the number of neurons of the BSTMP between Tfm and their control littermate males, while in the LC, Tfm males have a greater number of neurons than their control littermate males. These results show that the AR is involved in the control of neuron number in the LC but not in the BSTMP. Results based on the LC suggest that when females have a larger brain area than males, masculinization in males may be achieved through the AR, with androgens perhaps decreasing cell survival.

Morphometrical and neurochemical changes in the anteroventral subdivision of the rat medial amygdala during estrous cycle

The anteroventral subdivision of the medial amygdala (MeAV) is one of the vomeronasal structures involved in the control of hormonally dependent behaviors such as sexual and agonistic behaviors in rats. The present study investigates some anatomical and neurochemical parameters of this nucleus (volume, number of neurons, number of glial elements, and of NADPH-diaphorase-positive neurons) in females in two estrous cycle phases (diestrous and estrous) and in males. We also investigate the possible existence of adult neurogenesis in this nucleus in the females. Results showed that volume and estimated number of Nissl-stained neurons in the MeAV vary with the estrous cycle phase: estrous females have greater values than diestrous females. As a consequence of these variations, there is a transient sex difference between males and diestrous females. Two subpopulations of NADPH-diaphorase-positive neurons were detected: intensely stained and medium stained. The intensely stained neurons were more numerous in the estrous than the diestrous females. Neither BrdU nor GFAP inmunostaining revealed significant differences between the two groups, suggesting that adult cell generation, i.e., increases in the number of glial elements, has no significant role in the changes detected in the number of Nissl-stained sections. In conclusion, the MeAV shows functional diergism, due to plastic changes in the female rat brain probably linked to the increase of estradiol during estrous. Finally, these changes are probably functionally related to changes in the behaviors that are controlled through this nucleus.

Sex differences in the posteromedial cortical nucleus of the amygdala in the rat

IT has been hypothesized that the vomeronasal system (VNS), a complex neural network implicated in the control of reproductive behaviors, is sexually dimorphic. The posteromedial cortical amygdaloid nucleus (PMCo) belongs to the group of amygdaloid structures that receive direct olfactory input from the accessory olfactory bulb. In the present study we looked for sex differences in this nucleus in male and female adult rats and we found that the males had larger volumes and more neurons than the females. These results support the hypothesis that the VNS is a sexually dimorphic system.

Postnatal administration of dihydrotestosterone to the male rat abolishes sexual dimorphism in the accessory olfactory bulb: a volumetric study

The regulatory action of the non-aromatizable androgen dihydrotestosterone (DHT) on sexual differentiation of the volume of the rat accessory olfactory bulb (AOB) was studied. Postnatal treatment with DHT (180 micrograms/day) carried out daily between days 6 and 20 produced a drastic reduction in overall AOB size and that of its constituent neural layers in genetic males with respect to intact and control males. The volumetric measures found in DHT-treated males did not differ from those shown by the intact females. These results, which indicate a demasculinization and a feminization of the AOB volume in gonadally intact male rats induced by DHT, are discussed in relation to the presumably regulatory role of DHT on neuron populations during the sexual organizational process of the brain.

Sexual dimorphism in the vomeronasal system of the rabbit.

Studies have shown that the vomeronasal system (VNS), an olfactory neural network that participates in the control of reproductive physiology and behavior, is sexually dimorphic in the rat. These works have also shown two main characteristics of brain sexual dimorphism: (a) dimorphism appears in neural networks related to reproduction and (b) it can present two morphological patterns: one in which males present greater morphological measures than females (male > female) and another in which the opposite is true (female > male). The present work extends the hypothesis to the rabbit, as a representative species of Lagomorpha. In addition, the locus coeruleus (LC), which is known to send rich noradrenergic projections to VNS structures, was also studied. Sex differences were found in: (a) the number of mitral, and dark and light granule cells (female > male) of the accessory olfactory bulb (AOB); (b) the medial amygdala (Me) and its dorsal (Med) and ventral (Mev) subdivisions, males showing greater values than females in volume and number of neurons, while in the posteromedial cortical amygdala (PMCo or C(3)), females show greater density of neurons than males and (c) the posteromedial division of the bed nucleus of the stria terminalis (BSTMP) in which males have more neurons than females. No sex differences were seen in the bed nucleus of the accessory olfactory tract (BAOT) and the LC. These results evidence that, as it was observed in rodents, sex differences are also seen in the VNS of Lagomorpha and that these sex differences present the two morphological patterns seen in Rodentia. Differences between orders are discussed with respect to the species-specific physiological and behavioral peculiarities.

Early postnatal diazepam exposure alters sex differences in the rat brain

The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain.

Estradiol masculinizes the posteromedial cortical nucleus of the amygdala in the rat.

It has been demonstrated that the posteromedial cortical amygdaloid nucleus (PMCo), is sexually dimorphic. It is shown (Experiment 1) that male orchidectomy on the day of birth (D1) decreases the volume and number of neurons of the PMCo, while a single injection of propionate testosterone to the female on D1 masculinizes the PMCo in this gender. Since male gonadectomy on D1 (Experiment 2) is counteracted by a single injection of estradiol benzoate in males it has been suggested that the masculinization of the PMCo is due to the aromatization of testosterone to estradiol in this structure. These findings support the hypothesis that the development of sex differences in structures that belong to the vomeronasal system are due to the aromatization of testosterone to estradiol shortly after birth.