Rare origin of the sinoatrial node artery: an anatomic report and a brief review of the literature.

Several studies reported anatomical variations in the sinoatrial node artery (SANa). Here, we report a rare variation in the origin of the SANa on a human adult male cadaver. During dissection, we identified the SANa originating from a large atrial branch of the right coronary artery (RCA). This branch originates at the level of the inferior border of the heart and courses upwards. The initial part of this vessel is tortuous, and then it follows a straight path parallel to the RCA along the anterior surface of the right atrium. After this part, the artery curves posteriorly and to the left until it reaches the lower border of the right auricle, where it closely approaches the RCA. Finally, the artery runs posteriorly and to the right to follow a course along the medial wall of the right auricle and right atrium to reach a location close to the region of the junction of the superior vena cava and right atrium, where it follows its path buried in the myocardium. After perforating the myocardium, this vessel gives rise to branches that are distributed to both atria in addition to the SANa. The SANa runs to the sinoatrial node in a precaval (anterior to the superior vena cava) course. We also tried to characterize the vessels radiologically. The knowledge of the anatomical variations of the SANa is of the utmost importance for cardiologists and heart surgeons to better understand cardiac disease and accurately plan and execute cardiac interventions and surgical procedures.

High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology.

We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation.

Lateral rectus pulley concerning the orbital wall. Area of a stereotyped bony insertion.

Purpose: To examine the lateral rectus muscle pulley and its bony insertion concerning the orbital rim and periorbita. Design: Prospective. An observational anatomic study. Methods: Study population: Twenty postmortem orbits (10 right, 10 left) of 10 Caucasian cadavers (8 females, 2 males; age range at death, 57-100 years; median age, 79.5 years) fixed by the Thiel method.Intervention: The floor of the temporal fossa was exposed, and a bone window on the lateral wall of the orbit, posterior to the sphenozygomatic suture, was created, keeping the periorbita intact. The lateral canthus and lateral palpebral ligament were isolated and opened, and the eyelids were folded back. The frontozygomatic suture was identified, and the orbital septum opened adjacent to the orbital rim. The conjunctiva was opened at the limbus, and the lateral rectus insertion was isolated. The bone pillar containing the frontozygomatic suture and the insertion of the periorbita and the pulley was isolated and removed en bloc. The lateral rectus muscle was isolated and excised.Main outcome measures: Position of the pulley ring on the lateral rectus muscle belly and its bony attachment area in the lateral wall of the orbit. Results: The pulley bony attachment was roughly quadrilateral with an approximate area of 90 mm2, 3 mm (mean, range 1-5 mm) posteroinferior to the frontozygomatic suture and 1 mm posterior to the orbital rim. The anterior margin of the pulley sleeve was found at 21.0 mm (median, p25-75 20.0-22.8) from the scleral insertion. Conclusions: The lateral rectus pulley is stereotyped in its position in the muscle belly and its bony insertion, coinciding with the point of greatest adhesion of the periorbita to the anterior part of the lateral wall of the orbit.

Effects of High-Fat and High-Fat High-Sugar Diets in the Anxiety, Learning and Memory, and in the Hippocampus Neurogenesis and Neuroinflammation of Aged Rats.

High-caloric diets induce several deleterious alterations in the human body, including the brain. However, information on the effects of these diets on the elderly brain is scarce. Therefore, we studied the effects of 2 months of treatment with high-fat (HF) and high-fat-high-sugar (HFHS) diets on aged male Wistar rats at 18 months. Anxiety levels were analyzed using the open-field and plus-maze tests, while learning and memory processes were analyzed using the Morris water maze test. We also analyzed neurogenesis using doublecortin (DCX) and neuroinflammation using glial fibrillary acidic protein (GFAP). In aged rats, the HFHS diet impaired spatial learning, memory, and working memory and increased anxiety levels, associated with a reduction in the number of DCX cells and an increase in GFAP cells in the hippocampus. In contrast, the effects of the HF diet were lighter, impairing spatial memory and working memory, and associated with a reduction in DCX cells in the hippocampus. Thus, our results suggest that aged rats are highly susceptible to high-caloric diets, even if they only started in the elderly, with an impact on cognition and emotions. Furthermore, diets rich in saturated fats and sugar are more detrimental to aged rats than high-fat diets are.

Effects of aging on the cholinergic innervation of the rat ventral tegmental area: A stereological study.

Dopamine neurons in the ventral tegmental area (VTA) play a main role in processing both rewarding and aversive stimuli, and their response to salient stimuli is significantly shaped by afferents originating in the brainstem cholinergic nuclei. Aging is associated with a decline in dopaminergic activity and reduced response to positive reinforcement. We have used stereological techniques to examine, in adult and aged rats, the dopaminergic neurons and the cholinergic innervation of the VTA, and the cholinergic populations of the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei, which are the only source of cholinergic inputs to the VTA. In the VTA, there were no age-related variations in the number and size of tyrosine hydroxylase (TH)-immunoreactive neurons, but the density of cholinergic varicosities was reduced in aged rats. The total number of choline acetyltransferase (ChAT)-immunoreactive neurons in the PPT and LDT was unchanged, but their somas were hypertrophied in aged rats. Our results suggest that dysfunction of the cholinergic system might contribute for the age-associated deterioration of the brain reward system.

Surgical anatomy of the radial nerve in the arm: a cadaver study.

PURPOSE: The purpose of this study was to analyse the anatomic course of the radial nerve (RN) in the arm, in order to minimize the potential risk of surgical injury. METHODS: The study was performed in 19 embalmed upper extremities of 11 adult human cadavers. We measured: distance from deltoid insertion (DI) into the humerus to lateral epicondyle (LE); distance from RN piercing point into the lateral intermuscular septum (LIS) to three other points-DI, LE and RN division into superficial and deep terminal branches; distance between the LE and the RN division. To assess variability, we correlated the distances between the landmarks to the overall length of the arm. RESULTS: The RN was found to pierce the LIS within 31.6 mm of the most distal DI into the humerus. The mean distance between the entry point of RN in the LIS and the LE was 107.2 mm. The mean distance between RN perforating point in the LIS and RN division in its terminal branches was 86.4 mm. The DI-LE and the LIS-LE showed a moderate positive correlation with the length of the arm. CONCLUSION: We describe the DI relationship to the RN course and also report its proportion within overall arm length which has not been previously described. Using the arm length as reference, our results show that RN can be found to perforate on the LIS at a point distal to the DI by 11% and proximal to the LE by 38%.

Effects of chronic alcohol consumption and withdrawal on the cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei of the rat: An unbiased stereological study.

The brain cholinergic system comprises two main recognized subdivisions, the basal forebrain and the brainstem cholinergic systems. The effects of chronic alcohol consumption on the basal forebrain cholinergic nuclei have been investigated extensively, but there is only one study that has examined those effects on the brainstem cholinergic nuclei. The last one comprises the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei, which are known to give origin to the main cholinergic projection to the ventral tegmental area, a key brain region of the neural circuit, the mesocorticolimbic system, that mediates several behavioral and physiological processes, including reward. In the present study, we have examined, using stereological methods, the effects of chronic alcohol consumption (6 months) and subsequent withdrawal (2 months) on the total number and size of PPT and LDT choline acetyltransferase (ChAT)-immunoreactive neurons. The total number of PPT and LDT ChAT-immunoreactive neurons was unchanged in ethanol-treated and withdrawn rats. However, ChAT-immunoreactive neurons were significantly hypertrophied in ethanol-treated rats, an alteration that did not revert 2 months after ethanol withdrawal. These results show that prolonged exposure to ethanol leads to long-lasting, and potentially irreversible, cytoarchitectonic and neurochemical alterations in the brainstem cholinergic nuclei. These alterations suggest that the alcohol-induced changes in the brainstem cholinergic nuclei might play a role in the mechanisms underlying the development of addictive behavior to alcohol.

Chronic stress leads to long-lasting deficits in olfactory-guided behaviors, and to neuroplastic changes in the nucleus of the lateral olfactory tract.

A recent study reported that the integrity of the nucleus of the lateral olfactory tract (nLOT) is required for normal olfaction and for the display of odor-driven behaviors that are critical for species survival and reproduction. In addition to being bi-directionally connected with a key element of the neural circuitry that mediates stress response, the basolateral nucleus of the amygdala, the nLOT is a potential target for glucocorticoids as its cells express glucocorticoid receptors. Herein, we have addressed this hypothesis by exploring, first, if chronic variable stress (CVS) disrupts odor detection and discrimination, and innate olfactory-driven behaviors, namely predator avoidance, sexual behavior and aggression in male rats. Next, we examined if CVS alters the nLOT structure and if such changes can be ascribed to stress-induced effects on the activity of the main output neurons, which are glutamatergic, and/or of local GABAergic interneurons. Finally, we analyzed if the stress-induced changes are transient or, conversely, persist after cessation of CVS exposure. Our data demonstrate that CVS leads to severe olfactory deficits with inability to detect and discriminate between odors and to innately avoid predator odors. No effects of CVS on sexual and aggressive behaviors were observed. Results also showed that CVS leads to somatic hypertrophy of pyramidal glutamatergic neurons, which likely results from neuronal disinhibition consequent to the loss of inhibitory inputs mediated by GABAergic interneurons. Most of the CVS-induced effects persist beyond a 4-week stress-free period, suggesting long-lasting effects of chronic stress on the structure and function of the olfactory system.

The integrity of the nucleus of the lateral olfactory tract is essential for the normal functioning of the olfactory system.

The nucleus of the lateral olfactory tract (nLOT) is a relatively small component of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and connectivity patterns. Although it has been suggested that it might be involved in non-pheromonal olfactory-guided behaviors, particularly feeding, the functional implications of the nLOT have never been investigated. In view of this fact, we have tackled this subject by performing a series of behavioral tests and by quantifying biological and biochemical parameters in sexually naïve adult male rats that were submitted to bilateral excitotoxic lesions of the nLOT. nLOT-lesioned rats had severe olfactory deficits with inability to detect and discriminate between odors. Additionally, they did not display innate behavioral responses to biologically relevant chemosignals. Specifically, nLOT-lesioned rats did not show avoidance towards predator odors or aggressive behaviors towards intruders, and had severely impaired sexual behavior. In fact, nLOT lesions abolished preference for odors of receptive females, reduced chemoinvestigatory behavior and eliminated mounting behavior. nLOT-lesioned rats had normal circulating levels of testosterone, did not display anxiety- or depressive-like behaviors, and had unimpaired cognitive functions and fear acquisition and memory. Altogether, our results suggest that the nLOT integrity is required for the normal functioning of the olfactory system.

Nerve growth factor-induced plasticity in medial prefrontal cortex interneurons of aged Wistar rats.

The medial prefrontal cortex (mPFC) has been identified as a critical center for working and long-term memory. In this study, we have examined the expression of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in mPFC interneurons and the density of the mPFC cholinergic and dopaminergic innervation in cognitively-impaired aged Wistar rats. We also tested the possibility that the potential age-related changes might rely on insufficient neurotrophic support. The total number of NPY- and VIP-immunoreactive neurons and the density of vesicular acetylcholine transporter (VAChT)- and tyrosine hydroxylase (TH)-immunoreactive varicosities were estimated using stereological methods. The number of NPY-immunoreactive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased expression of NPY was fully reversed by intracerebroventricular administration of nerve growth factor. No differences in the density of VAChT- and TH-immunoreactive varicosities were found among all groups. Our results indicate that the reduced expression of NPY in the mPFC of aged rats can be ascribed to the age-associated loss of neurotrophic support, and raise the possibility that these changes might contribute for the cognitive decline that occurs during non-pathological aging.

Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus.

Induction and subcellular redistribution of progesterone receptor A and B by tamoxifen in the hypothalamic ventromedial neurons of young adult female Wistar rats.

The ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is a brain center for estrogen-dependent triggering of female sexual behavior upon progesterone receptor (PR) activation. We examined the agonistic and antagonistic actions of tamoxifen in this nucleus by analyzing its effects on the total number of PR-immunoreactive neurons, PR mRNA and protein levels, and subcellular location of PRs in ovariectomized Wistar rats. The results show that tamoxifen has no agonistic action in the number of PR-immunoreactive neurons, but increases PR expression and labeling in the nucleus and cytoplasm of VMNvl neurons that constitutively express PRs. As an antagonist, tamoxifen partially inhibited the estradiol-dependent increase in the number of PR-immunoreactive neurons and in PR mRNA and protein levels, without interfering with the subcellular location of the protein. We suggest that tamoxifen influence on PR expression in the VMNvl critically depends on the presence or absence of estradiol.

Age effects on the nucleus of the lateral olfactory tract of the rat.

The olfactory deficits that occur during aging influence the quality of life and have been regarded as a risk factor for malnutrition in the elderly. The nucleus of the lateral olfactory tract (nLOT) is a cortical nucleus of the pallial amygdala that has been implicated in feeding behavior. Here we present quantitative data on the anatomy of the nLOT in the adult rat and on the effects of age on its structure and neurochemistry. Total neuron numbers, neuronal volumes, and volumes of layers 1-3 of the nLOT were estimated in adult and old male rats using stereological techniques. We also estimated the total number of interneurons expressing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), and the numerical density of the nLOT cholinergic varicosities. Our data show that aging is associated with a reduction of the total neuron numbers in the nLOT, due to cell loss in layers 2 and 3. There were no age-related variations in neuronal volumes. Similarly, the volume of the nLOT was unchanged in aged rats, except in layer 3 where it was reduced. The numerical density of cholinergic varicosities was also unchanged in aged rats. Conversely, the total numbers of NPY- and VIP-immunoreactive neurons were reduced by 55% and 30%, respectively, in aged rats. These findings include the nLOT in the list of cortical olfactory structures susceptible to aging and raise the possibility that the age-related changes that occur in the nLOT might contribute for the decline in olfactory functions reported in normal aging.

Estrogen receptors α and ß have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons.

Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERß, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERß, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERß and/or the ERα-ERß interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERß, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERß activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERß increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERß have different effects on the levels and subcellular location of PRs in VMNvl neurons.

Effects of sex steroids and estrogen receptor agonists on the expression of estrogen receptor alpha in the principal division of the bed nucleus of the stria terminalis of female rats.

Estrogen actions on neurons of the principal division of the bed nucleus of the stria terminalis (BNSTpr) are essential for the regulation of female sexual behavior. However, little is known about the effects of estradiol and progesterone (P) on estrogen receptor alpha (ERα) expression in this nucleus. To study this subject, we used stereological methods to estimate the total number of ERα-immunoreactive (ERα-ir) neurons in the BNSTpr of female rats at each stage of the estrous cycle and of ovariectomized rats after administration of estradiol benzoate (EB) and/or P. To ascertain the percentage of ERα-positive neurons in the BNSTpr, the total number of neurons in this nucleus was also estimated. In order to identify the specific role played by the selective activation of each ER in the expression of ERα, ovariectomized rats were injected with the ERα agonist, propyl-pyrazole triol (PPT), or the ERß agonist, diaryl-propionitrile (DPN). Data show that ERα is expressed in 40-60% of the BNSTpr neurons and that the number of ERα-ir neurons is lowest at proestrus. This value is paralleled by the administration of EB. The number of ERα-ir neurons was not modified by P. PPT induced no changes in the number of ERα-ir neurons. Contrariwise, DPN induced a decrease in the total number of ERα-ir neurons to values similar to those of EB-treated rats. These results show that P has no effect in the modulation of ERα expression and demonstrate that estradiol regulation of ERα in BNSTpr neurons is mediated by activation of ERß.

Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence.

Role of plasma membrane estrogen receptors in mediating the estrogen induction of progesterone receptors in hypothalamic ventromedial neurons.

Progesterone is well known for its role in the modulation of sexual behavior. In the ventromedial nucleus (VMN), a part of the mediobasal hypothalamus that regulates sexual behavior in female rodents, estrogens induce the expression of progesterone receptors (PRs). This effect is known to be dependent on the activation of nuclear estrogen receptors (ERs). However, recent studies have documented estrogen activation of genomic transcription triggered by protein-protein phosphorylation cascades initiated at membrane receptors. The aim of this study was to examine if membrane-initiated estradiol (E2 ) stimulation is able to induce PR expression in the VMN or, at least, to modulate nuclear ER action. To achieve this goal, 2-month-old ovariectomized Wistar rats were injected bilaterally, in the vicinity of VMN, with free E2 and with E2 conjugated with bovine serum albumin (E2 BSA), alone or in sequence, by using a two-pulse injection paradigm. Stereological methods and western blot analysis were used to estimate the total number of PR-immunoreactive neurons in the VMN and the PR protein content of the VMN, respectively. The results showed that the administration of E2 BSA alone increases the number of PR-immunoreactive neurons and the expression level of PR protein to values similar to those resulting from E2 administration. They also showed that the sequential administration of E2 and E2 BSA potentiates the effects resulting from the injection of E2 or E2 BSA alone. These data provide the first evidence that membrane-initiated E2 stimulation is able to induce and to potentiate the genomic activation of PR expression in the VMN.

Nerve growth factor retrieves neuropeptide Y and cholinergic immunoreactivity in the nucleus accumbens of old rats.

The nucleus accumbens (NAc) contains high levels of neuropeptide Y (NPY), which is involved in the regulation of functions and behaviors that deteriorate with aging. We sought to determine if aging alters NPY expression in this nucleus and, in the affirmative, if those changes are attributable to the cholinergic innervation of the NAc. The total number and the somatic volume of NPY- and choline acetyltransferase-immunoreactive neurons, and the density of cholinergic varicosities were estimated in the NAc of adult (6 months old) and aged (24 months old) rats. In aged rats, the number of NPY neurons was reduced by 20% and their size was unaltered. The number of cholinergic neurons and the density of the cholinergic varicosities were unchanged, but their somas were hypertrophied. Nerve growth factor administration to aged rats further increased the volume of cholinergic neurons, augmented the density of the cholinergic varicosities, and reversed the age-related decrease in the number of NPY neurons. Our data show that the age-related changes in NPY levels in the NAc cannot be solely ascribed to the cholinergic innervation of the nucleus.

Effects of chronic alcohol consumption and withdrawal on the response of the male and female hypothalamic-pituitary-adrenal axis to acute immune stress.

The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the response to stress, and its activity is sexually dimorphic and modulated by sex steroids. Recent work indicates that HPA axis functioning is disturbed by chronic alcohol consumption and subsequent withdrawal in rats of both sexes, but particularly in females. To examine the influence of sex steroid hormones in HPA axis response to acute stress after ingestion of a 20% ethanol solution over 6months and subsequent withdrawal (2months), intact males, and estradiol- and oil-injected ovariectomized females received a single intraperitoneal injection of lipopolysaccharide (LPS). Six hours after LPS administration, corticosterone concentrations were increased in all male groups; however, in ethanol-treated rats they remained below those of control and withdrawn rats. mRNA levels of corticotrophin-releasing hormone (CRH) increased, and were identical in all groups after LPS stimulation, whereas those of vasopressin, although increased, remained below control levels. LPS stimulation elevated corticosterone concentrations in all oil-injected female groups, but did not alter those of estradiol-injected females. In oil- and estradiol-injected ethanol-treated females, CRH mRNA levels did not change in response to LPS stimulation, whereas those of vasopressin increased, but stayed below control levels. In withdrawn oil- and estradiol-injected females, CRH and vasopressin gene expression increased, but did not reach control levels. These data show that prolonged alcohol consumption produces long-lasting, possibly irreversible, changes in the neuroendocrine system that regulates the production of corticosteroids, and that these consequences are more profound in females, particularly when estrogen levels are low.

Sex steroid hormones regulate the expression of growth-associated protein 43, microtubule-associated protein 2, synapsin 1 and actin in the ventromedial nucleus of the hypothalamus.

The ventromedial nucleus of the hypothalamus is well known for its involvement in the regulation of the female reproductive behavior. The dendritic trees of neurons in its ventrolateral division (VMNvl), the dendritic spines, and the dendritic and spine synapses undergo alterations along the estrous cycle. Because these changes are conspicuous, we thought of interest to examine the influence of sex steroids in the levels of the structural proteins of axons and dendrites. The VMNvl of female rats at all phases of the estrous cycle was labeled for growth-associated protein-43, microtubule-associated protein 2, synapsin 1 and actin. The intensity of the labeling was measured using a modified Brightness-Area-Product method that is sensitive to variations the size of the VMN. The brightness per unit area of these proteins did not undergo significant variations over the estrous cycle, except synapsin 1 that was significantly reduced in diestrus relative to the remaining phases of the ovarian cycle. Conversely, the Brightness-Area-Product of all labeled proteins changed along the estrous cycle and was greater at proestrus than at all other phases. Our results show the presence of estrous cycle-related oscillations in the levels of the structural proteins that are involved in dendritic and synaptic plasticity.