Anterolateral ligament of the knee-Cadaver study in a Caucasian population / Ligamento anterolateral de la rodilla. Estudio en cadáver en una población caucásica

Introduction: Despite the recognized importance of the anterolateral ligament (ALL) in rotational stability of the knee, some studies still deny its role and even its existence. We studied the prevalence of the ALL in a Caucasian population, as well as its characteristics and anatomical relationships. Materials and methods: The study was performed on 20 knees from 10 embalmed cadavers. A lateral approach, as described by Steven Claes, was used and the relations of the ALL with the lateral epicondyle, lateral inferior genicular artery, lateral meniscus, Gerdy's tubercle and fibular head were recorded. Its length and its width were also measured. Results: The ALL was identified in 16 knees. Its origin was at a distance inferior to 1mm posterior and proximal to the lateral femoral epicondyle and insertion within a mean distance of 2.1±0.6mm from de tibial articular surface, 20.6±1.3mm from the Gerdy's tubercle and 20.3±1.2mm from the fibular head. In all cases ALL presented mutual fibers with the lateral meniscus. The length was 35.8±4.6mm and the width was 4.2±1.3/4.9±1.0/6.5±1.5mm at its proximal, middle and distal third, respectively. No difference was found between gender and the dimensions of the ligament. Conclusions: The ALL was found in 80% of the knees. Its origin is closely related to the lateral collateral ligament and its insertion is halfway between the fibular head and the Gerdy's tubercle. In all cases, we verified the connection between ALL and the lateral meniscus.(AU)

Introducción: Aunque ha sido reconocida la importancia del ligamento anterolateral (ALL) en la estabilidad rotacional de la rodilla, algunos estudios siguen negando su existencia. Estudiamos la prevalencia del ALL en una población caucásica, así como sus características y relaciones anatómicas. Métodos: El estudio se realizó en 20 rodillas de 10 cadáveres embalsamados. Se utilizó un abordaje lateral, como lo describe Steven Claes, y se registraron las relaciones del ALL con el epicóndilo lateral, la arteria genicular inferior lateral, el menisco lateral, el tubérculo de Gerdy y la cabeza del peroné. También se midió el ancho y el largo. Resultados: El ALL fue identificado en 16 rodillas. Su origen estaba a una distancia inferior a 1mm posterior y proximal al epicóndilo femoral lateral y su inserción a una distancia media de 2,1±0,6mm de la superficie articular tibial, 20,6±1,3mm de la tuberosidad de Gerdy y 20,3±1,2mm de la cabeza del peroné. En todos los casos se presentaban fibras mutuas con el menisco lateral. El largo fue de 35,8±4,6mm y el ancho fue de 4,2±1,3/4,9±1,0/6,5±1,5mm en su tercio proximal, medio y distal. Conclusiones: El ALL se encontró en el 80% de las rodillas. Su origen está íntimamente relacionado con el ligamento colateral lateral y su inserción se encuentra a media distancia entre la cabeza del peroné y el tubérculo de Gerdy. En todos los casos comprobamos la conexión entre el ALL y el menisco lateral.(AU)

[Artículo traducido] Ligamento anterolateral de la rodilla. Estudio en cadáver en una población caucásica / Anterolateral ligament of the knee-Cadaver study in a Caucasian population

Introduction: Despite the recognized importance of the anterolateral ligament (ALL) in rotational stability of the knee, some studies still deny its role and even its existence. We studied the prevalence of the ALL in a Caucasian population, as well as its characteristics and anatomical relationships. Materials and methods: The study was performed on 20 knees from 10 embalmed cadavers. A lateral approach, as described by Steven Claes, was used and the relations of the ALL with the lateral epicondyle, lateral inferior genicular artery, lateral meniscus, Gerdy's tubercle and fibular head were recorded. Its length and its width were also measured. Results: The ALL was identified in 16 knees. Its origin was at a distance inferior to 1mm posterior and proximal to the lateral femoral epicondyle and insertion within a mean distance of 2.1±0.6mm from de tibial articular surface, 20.6±1.3mm from the Gerdy's tubercle and 20.3±1.2mm from the fibular head. In all cases ALL presented mutual fibers with the lateral meniscus. The length was 35.8±4.6mm and the width was 4.2±1.3/4.9±1.0/6.5±1.5mm at its proximal, middle and distal third, respectively. No difference was found between gender and the dimensions of the ligament. Conclusions: The ALL was found in 80% of the knees. Its origin is closely related to the lateral collateral ligament and its insertion is halfway between the fibular head and the Gerdy's tubercle. In all cases, we verified the connection between ALL and the lateral meniscus.(AU)

Introducción: Aunque ha sido reconocida la importancia del ligamento anterolateral (ALL) en la estabilidad rotacional de la rodilla, algunos estudios siguen negando su existencia. Estudiamos la prevalencia del ALL en una población caucásica, así como sus características y relaciones anatómicas. Métodos: El estudio se realizó en 20 rodillas de 10 cadáveres embalsamados. Se utilizó un abordaje lateral, como lo describe Steven Claes, y se registraron las relaciones del ALL con el epicóndilo lateral, la arteria genicular inferior lateral, el menisco lateral, el tubérculo de Gerdy y la cabeza del peroné. También se midió el ancho y el largo. Resultados: El ALL fue identificado en 16 rodillas. Su origen estaba a una distancia inferior a 1mm posterior y proximal al epicóndilo femoral lateral y su inserción a una distancia media de 2,1±0,6mm de la superficie articular tibial, 20,6±1,3mm de la tuberosidad de Gerdy y 20,3±1,2mm de la cabeza del peroné. En todos los casos se presentaban fibras mutuas con el menisco lateral. El largo fue de 35,8±4,6mm y el ancho fue de 4,2±1,3/4,9±1,0/6,5±1,5mm en su tercio proximal, medio y distal. Conclusiones: El ALL se encontró en el 80% de las rodillas. Su origen está íntimamente relacionado con el ligamento colateral lateral y su inserción se encuentra a media distancia entre la cabeza del peroné y el tubérculo de Gerdy. En todos los casos comprobamos la conexión entre el ALL y el menisco lateral.(AU)

Anterolateral ligament of the knee-Cadaver study in a Caucasian population.

INTRODUCTION: Despite the recognized importance of the anterolateral ligament (ALL) in rotational stability of the knee, some studies still deny its role and even its existence. We studied the prevalence of the ALL in a Caucasian population, as well as its characteristics and anatomical relationships. MATERIALS AND METHODS: The study was performed on 20 knees from 10 embalmed cadavers. A lateral approach, as described by Steven Claes, was used and the relations of the ALL with the lateral epicondyle, lateral inferior genicular artery, lateral meniscus, Gerdy's tubercle and fibular head were recorded. Its length and its width were also measured. RESULTS: The ALL was identified in 16 knees. Its origin was at a distance inferior to 1mm posterior and proximal to the lateral femoral epicondyle and insertion within a mean distance of 2.1±0.6mm from de tibial articular surface, 20.6±1.3mm from the Gerdy's tubercle and 20.3±1.2mm from the fibular head. In all cases ALL presented mutual fibers with the lateral meniscus. The length was 35.8±4.6mm and the width was 4.2±1.3/4.9±1.0/6.5±1.5mm at its proximal, middle and distal third, respectively. No difference was found between gender and the dimensions of the ligament. CONCLUSIONS: The ALL was found in 80% of the knees. Its origin is closely related to the lateral collateral ligament and its insertion is halfway between the fibular head and the Gerdy's tubercle. In all cases, we verified the connection between ALL and the lateral meniscus.

Anterolateral ligament of the knee-Cadaver study in a Caucasian population. / [Artículo traducido] Ligamento anterolateral de la rodilla. Estudio en cadáver en una población caucásica.

INTRODUCTION: Despite the recognized importance of the anterolateral ligament (ALL) in rotational stability of the knee, some studies still deny its role and even its existence. We studied the prevalence of the ALL in a Caucasian population, as well as its characteristics and anatomical relationships. MATERIALS AND METHODS: The study was performed on 20 knees from 10 embalmed cadavers. A lateral approach, as described by Steven Claes, was used and the relations of the ALL with the lateral epicondyle, lateral inferior genicular artery, lateral meniscus, Gerdy's tubercle and fibular head were recorded. Its length and its width were also measured. RESULTS: The ALL was identified in 16 knees. Its origin was at a distance inferior to 1mm posterior and proximal to the lateral femoral epicondyle and insertion within a mean distance of 2.1±0.6mm from the tibial articular surface, 20.6±1.3mm from the Gerdy's tubercle and 20.3±1.2mm from the fibular head. In all cases ALL presented mutual fibers with the lateral meniscus. The length was 35.8±4.6mm and the width was 4.2±1.3/4.9±1.0/6.5±1.5mm at its proximal, middle and distal third, respectively. No difference was found between gender and the dimensions of the ligament. CONCLUSIONS: The ALL was found in 80% of the knees. Its origin is closely related to the lateral collateral ligament and its insertion is halfway between the fibular head and the Gerdy's tubercle. In all cases, we verified the connection between ALL and the lateral meniscus.

Effects of gonadal steroids and of estrogen receptor agonists on the expression of estrogen receptor alpha in the medial preoptic nucleus of female rats.

The medial preoptic nucleus (MPN) is a sexually dimorphic cell group of the medial preoptic area that plays a central role in the integration of olfactory and hormonal stimuli that modulate sexually differentiated behaviors. The influence of sex steroids in these behaviors is mediated through activation of estrogen receptors (ERs), which are highly expressed in this nucleus. Little is known about the effects of progesterone (P) or the selective activation of each ER subtype on the expression of estrogen receptor alpha (ERα) in the MPN of female rats. We have addressed this subject in the current investigation by estimating, using stereological tools, the total number of MPN neurons that express ERα in rats at each phase of the estrous cycle and in ovariectomized rats treated with estradiol benzoate (EB), P or the ERα- and estrogen receptor beta (ERß)-specific agonists. Results show that the total number of ERα-immunoreactive neurons does not change over the estrous cycle, except at proestrus when the number is reduced. A similar effect was observed after the administration of EB, but not of P. Results also show that the estradiol-induced down-regulation of the ERα is mediated by activation of both ER subtypes, and that ERß activation leads to a reduction in the total number of ERα-immunoreactive neurons that is twice that resulting from ERα activation. Present data suggest that ERα activation triggers a sort of negative feedback mechanism in MPN neurons that reduces its own expression, which might be of importance for the regulation of estradiol-dependent physiological and behavioral responses.

Lesions of the laterodorsal tegmental nucleus alter the cholinergic innervation and neuropeptide Y expression in the medial prefrontal cortex and nucleus accumbens.

The effects of the ibotenic acid infused into the area of the laterodorsal tegmental nucleus (LDT) of rats on the expression of cortical and accumbal neuropeptides were assessed. The effects of this manipulation were determined in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) by estimating the numerical density of varicosities immunoreactive for vesicular acetylcholine transporter and the total number of NAc neurons immunoreactive for choline acetyltransferase (ChAT) and neuropeptide Y (NPY) as well as the total number of mPFC neurons immunoreactive for NPY and vasoactive intestinal polypeptide (VIP). In LDT-lesioned rats, the density of the cholinergic varicosities was reduced in the ventral divisions of the mPFC and in all divisions of the NAc. In addition, in these rats, the total number of NPY-immunoreactive neurons was reduced in all subregions of the mPFC and in the NAc. Conversely, the total number of VIP-immunoreactive neurons in the mPFC and of ChAT-immunoreactive neurons in the NAc did not differ between LDT- and sham-lesioned rats. These data provide the first direct evidence for a relationship between selective damage of LDT cholinergic neurons and decreased expression of NPY in the mPFC and NAc. They also reveal that different types of cortical and accumbal interneurons respond differently to the cholinergic denervation induced by LDT lesions.

Role of estrogen receptor α and ß in the induction of progesterone receptors in hypothalamic ventromedial neurons.

The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is critical for the regulation of female sexual behavior. VMNvl neurons express PRs and both types of estrogen receptors (ERα and ERß), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvl of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ERα, propyl-pyrazole triol (PPT), and of the ERß, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons. The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvl does not involve solely the activation of the ERα and suggests that it might also implicate the activation of membrane receptors. The present results also show that ERß activation averts the action of ERα in the induction of PRs.

Regulation of ERα protein expression by 17ß-estradiol in cultured neurons of hypothalamic ventromedial nucleus.

The activation of the subtype α of estrogen receptors (ERα) in the hypothalamic ventromedial nucleus (VMNvl) is required to stimulate female sexual receptivity. Moreover, the hormone was found to govern the expression of the receptor. Its removal due to ovariectomy and subsequent substitution suggest that the hormone down-regulates the expression of ERα. In contrast, in normally cycling animals the expression of the receptor peaks at proestrus, the phase of highest concentration of 17ß-estradiol in estrous cycle. Therefore, in this study we examined the influence of the hormone on ERα expression in primary dissociated cultures of neurons isolated from the VMNvl of young adult female rats. Measurements of ERα immunofluorescence revealed that both supraphysiological and physiological concentrations of 17ß-estradiol increase the expression of ERα. Analyses with selective agonists showed that both nuclear ERs are able to mediate the action of the hormone. However, the activation of ERα had a stronger effect on the expression of its own receptor than the activation of ERß. Simultaneous activation of both receptors attenuated the influence of ERα alone. Physiological concentrations of progesterone were found to revoke the effect of 17ß-estradiol, whereas the expression of ERα is up-regulated by progesterone alone. These data indicate that the expression of ERα in VMNvl neurons is under the control of both types of nuclear ERs and, in addition, progesterone receptors (PRs). The particular contribution of the receptors is dependent on their level of expression and the hormonal context. In neurons expressing high quantity of ERα, ERß attenuates the overall expression of the receptor, whereas in cells containing mostly ERß it contributes to the up-regulation of ERα synthesis. Simultaneous activation of ERs and PRs reverses the influences of the receptors due to inter-inhibition of their transcriptional activities.

Effects of estrogens and progesterone on the synaptic organization of the hypothalamic ventromedial nucleus.

The majority of the studies on the actions of estrogens in the ventrolateral part of the hypothalamic ventromedial nucleus (VMNvl) concern the factors that modulate the receptive component of the feminine sexual behavior and the expression of molecular markers of neuronal activation. To further our understanding of the factors that regulate synaptic plasticity in the female VMNvl, we have examined the effects of estradiol and progesterone, and of estrogen receptor (ER) subtype selective ligands on the number of dendritic and spine synapses established by individual VMNvl neurons and on sexual behavior. In contrast to earlier studies that analyzed synapse densities, our results show that exogenous estradiol increases the number of spine as well as of dendritic synapses, irrespective of the dose and regimen of administration. They also reveal that an effective dose of estradiol administered as one single pulse induces the formation of more synapses than the same dose administered as two pulses on consecutive days. Our results further show that both ER subtypes are involved in the mediation of the synaptogenic effects of estrogens on VMNvl neurons since the administration of the selective ERalpha, propyl-pyrazole-triol (PPT), and ERbeta, diarylpropionitrile (DPN), agonists induced a significant increase in the number of synapses that, however, was more exuberant for PPT. Despite its relevant role in feminine sexual behavior, progesterone had no synaptogenic effect in the VMNvl as no changes in synapse numbers were noticed in rats treated with progesterone alone, with estradiol followed by progesterone or with the antiprogestin mifepristone (RU486). Except for the sequential administration of estradiol and progesterone, none of the regimens was associated with lordosis response to vaginocervical stimulation. Therefore, from the sex steroids that undergo cyclic variations over the estrous cycle, only estrogens, acting through both ERalpha and ERbeta, play a key role in the activation of the neural circuits involving the ventromedial nucleus of the hypothalamus.

Neuronal organelles and nuclear pores of hypothalamic ventromedial neurons are sexually dimorphic and change during the estrus cycle in the rat.

Neurons in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) become hypertrophied when exposed to high estrogen levels, an effect that has been observed after estrogen treatment of ovariectomized rats as well as during the proestrus stage of the ovarian cycle. In an attempt to examine whether the neuronal hypertrophy noticed in these conditions reflects metabolic activation of the neurons we have examined, using quantitative methods, the cytoplasmic organelles involved in protein synthesis and the nuclear pores of VMNvl neurons from females on proestrus, when estrogen levels are high, and on diestrus, when estrogen levels are low. Because VMNvl neurons are sexually dimorphic with respect to their size we have performed, in parallel, similar analyses in neurons from age-matched male rats. Our results show that the volume and the surface area of the rough endoplasmic reticulum (RER) and Golgi apparatus are increased at proestrus. They also show that the density of nuclear pores is greater in males than in females whereas the volume and the surface area of the RER and Golgi apparatus are sexually dimorphic only at specific phases of the ovarian cycle: the male-female differences are notorious in the RER when females are on diestrus and in the Golgi apparatus when they are on proestrus. Given that the size of the RER and of the Golgi apparatus correlates with the level of neuronal protein synthesis, data obtained in this study suggest that the sex-related differences and the estrus cycle variations in neuronal size reflect corresponding differences and fluctuations in the metabolic activity of VMNvl neurons.

Basal forebrain neurons modulate the synthesis and expression of neuropeptides in the rat suprachiasmatic nucleus.

We tested the hypothesis that efferents from the nucleus basalis magnocellularis (NBM) play a direct role in the regulation of neuropeptide synthesis and expression by neurons of the rat suprachiasmatic nucleus (SCN). Adult male rats in which the NBM was destroyed with quinolinic acid, either unilaterally or bilaterally, were compared with rats injected with physiological saline and with control rats. The estimators used to assess the effects of cholinergic deafferentation on the neuroanatomy and neurochemistry of the SCN were the total number of SCN neurons, the total number and somatic size of SCN neurons producing vasopressin (VP) and vasoactive intestinal polypeptide (VIP), and the respective mRNA levels. Bilateral destruction of the NBM did not produce cell death in the SCN, but caused a marked reduction in the number and somatic size of SCN neurons expressing VP and VIP, and in the mRNA levels of these peptides. The decrease in the number of VP- and VIP-producing neurons provoked by unilateral lesions was less striking than that resulting from bilateral lesions. It was, however, statistically significant in the ipsilateral hemisphere, but not in the contralateral hemisphere. The results show that the reduction of cholinergic inputs to the SCN impairs the synthesis, and thereby decreases the expression of neuropeptides by SCN neurons, and that the extent of the decline correlates with the amount of cholinergic afferents destroyed. This supports the notion that acetylcholine plays an important, and direct role in the regulation of the metabolic activity of SCN neurons.

Dendritic changes in the hippocampal formation of AIDS patients: a quantitative Golgi study.

We have previously shown that in the hippocampal formation of patients with acquired immunodeficiency syndrome (AIDS) there is neuronal atrophy, without cell loss. Because reductions in neuronal size are suggestive of associated neuritic alterations, we decided to study the dendritic trees of the main neuronal populations in the hippocampal formation. Material was obtained in five male AIDS patients and five male controls. After Golgi impregnation, the dendritic arborizations of dentate granule and hilar basket cells, and of CA3 and CA1 pyramidal cells, were hand traced, and their segments classified, counted and measured. We found an impoverishment of the dendritic trees in all neuronal populations in the AIDS group, which was more striking in the hilus and CA3 field. Specifically, hilar neurons had fewer dendritic segments, and reduced branching density and dendritic extent; in CA3 pyramids there was a decrease in the number of terminal segments in the basal trees, and a reduction in the total number of segments, number of medium order terminals, dendritic branching density and dendritic extent in the apical trees. In CA1 pyramids, the terminals were shorter in the apical trees and the dendritic spine density decreased in the basal trees, whereas in granule cells only the dendritic spine density was reduced in AIDS patients. Subtle signs suggestive of dendritic reorganization were observed. These results point to a regional vulnerability of the hippocampal formation to HIV infection, and might contribute to explaining the occurrence of dementia, as a consequence of overall reduction in the hippocampal neuronal receptive surface.

Nerve growth factor prevents cell death and induces hypertrophy of basal forebrain cholinergic neurons in rats withdrawn from prolonged ethanol intake.

We have previously reported that the hippocampal cholinergic fiber network is severely damaged in animals withdrawn from ethanol, and that a remarkable recovery in fiber density occurs following hippocampal grafting, a finding that we suggested to be underpinned by the graft production of neurotrophic factors, which are known to be decreased after ethanol exposure. It is widely accepted that nerve growth factor (NGF) signals the neurons of the brain cholinergic system, including those of the medial septum/vertical limb of the diagonal band of Broca (MS/VDB) nuclei, from which the septohippocampal projection arises. Because neurons in these nuclei are vulnerable to ethanol consumption and withdrawal we thought of interest to investigate, in withdrawn rats previously submitted to a prolonged period of ethanol intake, the effects of intraventricular delivery of NGF upon the MS/VDB cholinergic neurons. Stereological methods were applied to estimate neuron numbers and neuronal volumes in choline acetyltransferase (ChAT)-immunostained and Nissl-stained material. We have found that in ethanol-fed rats there was a significant reduction in the total number of Nissl-stained and cholinergic neurons in the MS/VDB, and that the suppression of ethanol intake further decreased neuron numbers. In addition, the somatic size of ChAT-IR neurons was reduced by ethanol intake, and withdrawal further aggravated neuronal atrophy. NGF treatment prevented the withdrawal-associated loss, and induced hypertrophy, of cholinergic neurons. These findings show that exogenous NGF protects the phenotype and prevents the withdrawal-induced degeneration of cholinergic neurons in the MS/VDB. These effects might be due to the trophic action of NGF upon the basal forebrain cholinergic neurons, including the hippocampal fiber network that conveys this neurotrophin retrogradely to the MS/VDB, and/or upon their targets, that is, the hippocampal formation neurons.

Differential effects of the aging process on the morphology of the hypothalamic ventromedial nucleus of male and female rats.

We investigated the effects of aging on the neuroanatomical sex dimorphisms of the rat hypothalamic ventromedial nucleus (VMN). Stereological methods were used to estimate the volume of the VMN and the total number and size of its neurons, including their dendritic trees, in males and females aged 6 and 24 months. No cell loss was detected in aged rats. However, in aged females, the volume of the VMN and the somatic size of its neurons were increased, whereas in aged males the dendritic spine density was augmented. Due to these gender-specific effects, the male-female differences observed in the morphology of the VMN in adult rats were annulled in aging. Our findings support the notion that some structural sex dimorphisms in the brain are not stable throughout the life span.

Nerve growth factor restores mRNA levels and the expression of neuropeptides in the suprachiasmatic nucleus of rats submitted to chronic ethanol treatment and withdrawal.

Chronic ethanol treatment and withdrawal from alcohol decrease the synthesis and expression of neuropeptides in the hypothalamic suprachiasmatic nucleus. Given the existing evidence that neurotrophins modulate the synthesis and expression of neurotransmitters/neuromodulators in the mature brain, we have hypothesized that such alterations might result from the reduced biological activity or brain content of neurotrophic factors. To test this possibility, nerve growth factor (NGF) was delivered intraventricularly, over a 4-week period, to rats submitted to ethanol treatment for 6 months and to withdrawn rats. Vasopressin (AVP) and vasoactive intestinal polypeptide (VIP), and the respective mRNAs were detected by immunocytochemistry and in situ hybridization histochemistry, and their levels estimated using stereological methods and densitometry. In ethanol-treated and withdrawn rats, NGF produced increases in the number of AVP- and VIP-immunostained neurons to values identical to those of controls. Corresponding variations were detected in AVP and VIP mRNA levels, which indicates that NGF restored the expression of AVP and VIP by enhancing neuropeptide synthesis. These findings show that NGF can correct the changes induced by chronic ethanol treatment and withdrawal in the gene expression and protein content of the neuropeptides synthesized by suprachiasmatic neurons. They also reveal that NGF plays an important role in the maintenance of the neurochemical phenotype of the suprachiasmatic nucleus in the adult rat. Because suprachiasmatic neurons do not express trkA, NGF might have exerted its effects either through direct signalling of suprachiasmatic neurons via p75(NTR) activation or, indirectly, by enhancing the activity of the cholinergic and/or glutamatergic afferents to the suprachiasmatic nucleus, or both.

Influence of sex and estrus cycle on the sexual dimorphisms of the hypothalamic ventromedial nucleus: stereological evaluation and Golgi study.

Neurons in the ventromedial nucleus of the hypothalamus (VMN) display structural and biochemical sex differences in response to estrogen. Despite this fact, reports on sex differences in the morphology of the VMN are restricted to its volume and synaptic patterning. The aim of this study was to characterize the neuroanatomical sexual dimorphisms in the VMN and to investigate whether endogenous changes in ovarian steroid secretion influence such dimorphisms. The VMN of adult male rats and intact, aged-matched female rats killed on proestrus and diestrus day 1 was examined by using stereological methods applied to conventionally stained sections and Golgi-impregnated material. The VMN contained 55,000 neurons in rats of both sexes, but its volume was, on average, 1.25 times larger in males than in females. The volume was greater in proestrus than in diestrus rats due to parallel changes in the neuronal somatic size. Unlike the dorsomedial division, neurons in the ventrolateral division had longer dendritic trees in proestrus than in diestrus females and males. The spine density was consistently higher in females than in males in both VMN divisions. In addition, in the ventrolateral part the magnitude of the sex differences varied across the estrus cycle, and reached the greatest value when females were in proestrus. The volume of the neuropil was significantly larger in males than in females, and was not affected by the estrus phase. Our results reveal that the magnitude of the neuroanatomical sex differences in the VMN vary across the estrus cycle due to the trophic influence of estrogen upon its neurons. They also show that the fundamental sex difference in the structure of the VMN is accounted for by the neuropil components.

Sexual dimorphism in the subiculum of the rat hippocampal formation.

Data accumulated over the last years demonstrate that the hippocampal formation of rodents is sexually dimorphic with respect to its functional attributes. Neuroanatomical substrates that might contribute to explain these gender-related differences have been described in the dentate gyrus, and in the CA3 and CA1 hippocampal fields. However, the subiculum, the source of the major efferent projection of the hippocampal formation, has not been searched for the presence of sex-related differences. To address this issue, we have used stereological methods applied to adult rats of both sexes to estimate the volume of the subiculum, the total number of subicular neurons, and the total number and size of the synapses established by subicular neurons. The apical dendritic trees of Golgi-impregnated subicular neurons were also quantitatively analyzed. We have found that the volume of the subiculum and of its neuronal layer, and the total number of subicular neurons were greater in males than in females. Conversely, the total dendritic length of the apical arborization of the subicular neurons, and the number of dendritic spines and axospinous synapses were higher in females than in males. However, the size of the postsynaptic densities of the individual synapses was smaller in female than in male rats and, as a result, the surface area of the total active synaptic zones did not differ between the sexes. These findings provide an additional morphological clue for the comprehension of the sex dimorphisms within the hippocampal circuitries and, consequently, for a better understanding of the functional sex differences ascribed to the hippocampal formation.

AIDS does not alter the total number of neurons in the hippocampal formation but induces cell atrophy: a stereological study.

Although cognitive dysfunction is a common finding in patients with acquired immunodeficiency syndrome (AIDS) its pathogenesis remains controversial. Given the involvement of the hippocampal formation in the processing of cognitive information and the scarcity of quantitative studies in this brain region, we have examined, using stereological methods, the hippocampal formations of AIDS patients. The study was performed in ten AIDS patients and ten age-matched controls. All cases were male. The Principle of Cavalieri was applied to estimate the volume of the layers of the dentate gyrus and of the CA3 and CA1 hippocampal fields. The fractionator and the nucleator were used as estimators of the total number, and mean somatic and nuclear volumes of the neurons in the cell-containing layers of all hippocampal subdivisions. No cell death was detected in AIDS patients but the global volume of their hippocampal formations was significantly decreased due to the reduced volume of its layers, mainly the cell-containing layers. Furthermore, the somatic and nuclear volumes of the neurons in the hippocampal formation were significantly decreased in AIDS patients. No correlation was found between the estimates obtained and the presence or absence of neurological involvement. Our results show that neurons in the hippocampal formation of AIDS patients display marked morphological changes, despite the maintenance of their total number. These alterations are likely to lead to dysfunction of the hippocampal circuitries and, thus, might contribute to explaining the dementia features which occur in this condition.

Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement.

We recently demonstrated that stress-induced cognitive deficits in rats do not correlate with hippocampal neuronal loss. Working on the premise that subtle structural changes may however be involved, we here evaluated the effects of chronic stress on hippocampal dendrite morphology, the volume of the mossy fiber system, and number and morphology of synapses between mossy fibers and CA3 dendritic excrescences. To better understand the mechanisms by which stress exerts its structural effects, we also studied these parameters in rats given exogenous corticosterone. Further, to search for signs of structural reorganization following the termination of the stress and corticosterone treatments, we analysed groups of rats returned to treatment-free conditions. All animals were assessed for spatial learning and memory performance in the Morris water maze. Consistent with previous findings, dendritic atrophy was observed in the CA3 hippocampal region of chronically stressed and corticosterone-treated rats; in addition, we observed atrophy in granule and CA1 pyramidal cells following these treatments. Additionally, profound changes in the morphology of the mossy fiber terminals and significant loss of synapses were detected in both conditions. These alterations were partially reversible following rehabilitation from stress or corticosterone treatments. The fine structural changes, which resulted from prolonged hypercortisolism, were accompanied by impairments in spatial learning and memory; the latter were undetectable following rehabilitation. We conclude that there is an intimate relationship between corticosteroid levels, hippocampal neuritic structure and hippocampal-dependent learning and memory.