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Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced Perceptual Functioning model explains the connection between ASC, savant traits, and giftedness more seamlessly, and their co-emergence with atypical sexual differentiation. Overexcitability of primary sensory inputs generates a relative enhancement of local to global processing of stimuli, hindering the abstraction of communication signals, in contrast to the extraordinary local information processing skills in some individuals. Weaker inhibitory function through gamma-aminobutyric acid type A (GABAA) receptors and the atypicality of synapse formation lead to this difference, and the formation of unique neural circuits that process external information. Additionally, deficiency in monitoring inner sensory information leads to alexithymia (inability to distinguish one's own emotions), which can be caused by hypoactivity of estrogen and oxytocin in the interoceptive neural circuits, comprising the anterior insular and cingulate gyri. These areas are also part of the Salience Network, which switches between the Central Executive Network for external tasks and the Default Mode Network for self-referential mind wandering. Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases. It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations. [ABSTRACT FROM AUTHOR]

Amyloid beta 1-42 (Aβ42) aggregates acutely impair hippocampal long-term potentiation (LTP) of synaptic transmission, and 17β-estradiol is crucial for hippocampal LTP. We tested whether boosting the synthesis of neural-derived 17β-estradiol (nE2) saves hippocampal LTP by the neurotoxic action of Aβ42. Electrophysiological recordings were performed to measure dentate gyrus (DG) LTP in rat hippocampal slices. Using a pharmacological approach, we tested the ability of nE2 to counteract the LTP impairment caused by acute exposure to soluble Aβ42 aggregates. nE2 was found to be required for LTP in DG under physiological conditions. Blockade of steroid 5α-reductase with finasteride, by increasing nE2 synthesis from testosterone (T), completely recovered LTP in slices treated with soluble Aβ42 aggregates. Modulation of the glutamate N-methyl-D aspartate receptor (NMDAR) by memantine effectively rescued the LTP deficit observed in slices exposed to Aβ42, and memantine prevented LTP reduction observed under the blocking of nE2 synthesis. nE2 is able to counteract Aβ42-induced synaptic dysfunction. This effect depends on a rapid, non-genomic mechanism of action of nE2, which may share a common pathway with glutamate NMDAR signaling. [ABSTRACT FROM AUTHOR]

The interaction between endocrine and vestibular systems remains poorly documented so far, despite numerous observations in humans and animals revealing direct links between the two systems. For example, dizziness or vestibular instabilities often accompany the menstrual cycle and are highly associated with the pre-menopause period, while sex hormones, together with their specific receptors, are expressed at key places of the vestibular sensory network. Similarly, other hormones may be associated with vestibular disorders either as causal/inductive factors or as correlates of the pathology. This review was carried out according to the PRISMA method, covering the last two decades and using the MEDLINE and COCHRANE databases in order to identify studies associating the terms vestibular system and/or vestibular pathologies and hormones. Our literature search identified 646 articles, 67 of which referred directly to vestibular dysfunction associated with hormonal variations. While we noted specific hormonal profiles depending on the pathology considered, very few clinical studies attempted to establish a direct link between the expression of the vestibular syndrome and the level of circulating hormones. This review also proposes different approaches to shed new light on the link between hormones and vestibular disorders, and to improve both the diagnosis and the therapeutic management of dizzy patients. [ABSTRACT FROM AUTHOR]

Purpose: Foot sole cooling increases vestibular-evoked balance responses, but less is known about foot dorsum temperature alterations. The purpose was to determine whether decreasing cutaneous receptor sensitivity via foot dorsum cooling modulates the vestibular control of balance. Methods: Eighteen participants (9 males; 9 females) stood quietly on a force plate with feet together, eyes closed, and head rotated leftward during 4, 90-s trials (2 control; 2 cooled) of continuous electrical vestibular stimulation (EVS). Icepacks placed on the dorsum of both feet for 15 min induced cooling and remained throughout the EVS trials. Monofilament testing was performed at multiple locations before and after cooling to determine tactile detection thresholds. T-type thermocouples monitored skin temperature over the tibialis anterior, soleus, foot dorsum and arch of the right leg. Vestibular-evoked balance responses were characterized using time (cumulant density) and frequency (coherence and gain) domain analyses to determine the relationship between the EVS input and motor output (anteroposterior force—AP force; right medial gastrocnemius electromyography—MG EMG). Results: Skin temperature of the foot dorsum and arch decreased ~ 70 and 15%, respectively during cooling (p < 0.05), but was unaltered at other locations (p ≥ 0.10). Detection thresholds for the foot dorsum increased following cooling (p < 0.05). Surprisingly, cooling reduced EVS-AP force and EVS-MG EMG coherence and gain at multiple frequencies, and peak-to-peak amplitude compared to control (p < 0.05). Conclusion: Our results indicate that vestibular-driven balance responses are reduced following foot dorsum cooling, likely owing to alterations in cutaneous mechanoreceptor sensitivity and subsequent alterations in the transformation of vestibular cues for balance control. [ABSTRACT FROM AUTHOR]

Cerebellar‐dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids—mainly referred to as estrogens—may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo‐vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular‐motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular‐motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites. [ABSTRACT FROM AUTHOR]

The vestibular system exerts control over various functions through neural pathways that are not yet fully mapped. Functional dysregulations or tissue lesions at different levels of the peripheral and the central vestibular networks can alter these different functions, causing a wide variety of symptoms, ranging from posturo-locomotor alterations to psychiatric syndromes such as PPPD, including the deregulation of the main biological functions. These different symptoms differ by their expression kinetics (they each appear and regress with their own kinetics) by the targets affected (muscles, organs, and brain areas) and by the sensitivity specific to each individual. Vestibular pathologies thus cover a mosaic of distinct effects, and they involve various effectors—which constitute the many markers of their different types and stages. It is therefore crucial, to predict the onset of a vertigo syndrome, to follow its temporal course, or to monitor the impact of therapeutic approaches, and to have specific and reliable biomarkers. Hormonal variations are among the possible sources of biomarkers for neurotology. We know that specific hormonal profiles can promote the appearance of vestibular disorders. We also know that the expression of vertigo syndrome is accompanied by measurable hormonal variations. The link between endocrine deregulation and vestibular alterations therefore no longer needs to be proven. However, there are still few data on their precise correlations with the vertigo syndrome. This study was undertaken with the aim to deliver an extensive review of the hormonal alterations linked to vestibular disorders. A review of the literature covering the last two decades was carried out using the MEDLINE and COCHRANE databases in order to identify studies associating the terms vestibular system or vestibular pathologies and hormones. Bibliographic data provides several outcomes in terms of therapeutic innovation in the diagnosis and therapeutic follow-up of vestibular pathologies. [ABSTRACT FROM AUTHOR]

The present study explores the impact of metabotropic glutamate receptor (mGluR) activation on activity-dependent synaptic plasticity (ADSP) and the intrinsic membrane properties of lumbar motoneurons (MNs) using a combination of biochemical, pharmacological, electrophysiological and behavioral techniques. Using spinal cord slices from C57BL/6JRJ mice at two developmental stages, 1-3 and 8-12 postnatal days (P1-P3; P8-P12, respectively), we found that ADSP expressed at glutamatergic synapses between axons conveyed in the ventrolateral funiculus (VLF) and MNs, involved mGluR activation. Using specific agonists of the three groups of mGluRs, we observed that mGluR stimulation causes subtype-specific and developmentally regulated modulation of the ADSP and synaptic transmission at VLF-MN synapses as well as the intrinsic membrane properties of MNs. RT-qPCR analysis revealed a downregulation of mGluR gene expression with age in the ventral part of the lumbar spinal cord. Interestingly, the selective harvest by laser microdissection of MNs innervating the Gastrocnemius and Tibialis anterior muscles unraveled that the level of Grm2 expression is higher in Tibialis MNs compared to Gastrocnemius MNs suggesting a specific mGluR gene expression profile in these two MN pools. Finally, we assessed the functional impact of mGluR modulation on electrically induced bouts of fictive locomotion in the isolated spinal cord preparation of P1-P3 mice, and in vivo during spontaneous episodes of swimming activity in both P1-P3 and P8-P12 mouse pups. We observed that the mGluR agonists induced distinct and specific effects on the motor burst amplitudes and period of the locomotor rhythms tested and that their actions are function of the developmental stage of the animals. Altogether our data show that the metabotropic glutamatergic system exerts a complex neuromodulation in the developing spinal lumbar motor networks and provide new insights into the expression and modulation of ADSP in MNs. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the disparity in locomotor and spatial memory deficits caused by left- or right-sided unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL) and to examine the effects of galvanic vestibular stimulation (GVS) on the deficits over 14 days. Five experimental groups were established: the left-sided and right-sided UL (Lt.-UL and Rt.-UL) groups, left-sided and right-sided UL with bipolar GVS with the cathode on the lesion side (Lt.-GVS and Rt.-GVS) groups, and a control group with sham surgery. We assessed the locomotor and cognitive-behavioral functions using the open field (OF), Y maze, and Morris water maze (MWM) tests before (baseline) and 3, 7, and 14 days after surgical UL in each group. On postoperative day (POD) 3, locomotion and spatial working memory were more impaired in the Lt.-UL group compared with the Rt.-UL group (p < 0.01, Tamhane test). On POD 7, there was a substantial difference between the groups; the locomotion and spatial navigation of the Lt.-UL group recovered significantly more slowly compared with those of the Rt.-UL group. Although the differences in the short-term spatial cognition and motor coordination were resolved by POD 14, the long-term spatial navigation deficits assessed by the MWM were significantly worse in the Lt.-UL group compared with the Rt.-UL group. GVS intervention accelerated the vestibular compensation in both the Lt.-GVS and Rt.-GVS groups in terms of improvement of locomotion and spatial cognition. The current data imply that right- and left-sided UVD impair spatial cognition and locomotion differently and result in different compensatory patterns. Sequential bipolar GVS when the cathode (stimulating) was assigned to the lesion side accelerated recovery for UVD-induced spatial cognition, which may have implications for managing the patients with spatial cognitive impairment, especially that induced by unilateral peripheral vestibular damage on the dominant side. [ABSTRACT FROM AUTHOR]

Background: Nandrolone Decanoate (ND) is one of the most popular androgenic anabolic steroids (AASs) compounds that is widely abused during adolescence. Despite clear evidence about the effects of ND on hippocampal synaptic plasticity, its complex underlying mechanisms of action have remained elusive. Therefore, the aim of this study is to evaluate the role of P450 aromatase in the mediation of ND effects on hippocampal CA1 synaptic plasticity during adolescence in male rats. Material and Methods: In the present study, the rats were divided into four groups: Control group received DMSO, while other experimental groups received ND (60 µg/2.5 µL), anastrozole (1 µg/2.5 µL), and co-adminstration of anastrozole (1 µg/2.5 µL) and ND (60 µg/2.5 µL) for 4 days. Then, Field excitatory postsynaptic potential (fEPSP) and Population spikes (PS) magnitudes were investigated in the hippocampal CA1 area. Results: Electrophysiological results indicated higher fEPSP-LTP magnitude in the ND-treated group compared to DMSO-treated group (P < 0.05). Also, the results of field potential recording showed that anastrozole alone had not a significant effect on fEPSP-LTP magnitude, while pre-administration of anastrozole abolished the ND improvement effects on fEPSP-LTP magnitude. Conclusion: This study presented evidence supporting the involvement of aromatase in improvement effects of ND on hippocampal synaptic plasticity in adolescent male rats. [ABSTRACT FROM AUTHOR]

Vestibular and optokinetic space is represented in three-dimensions in vermal lobules IX-X (uvula, nodulus) and hemisphere lobule X (flocculus) of the cerebellum. Vermal lobules IX-X encodes gravity and head movement using the utricular otolith and the two vertical semicircular canals. Hemispheric lobule X encodes self-motion using optokinetic feedback about the three axes of the semicircular canals. Vestibular and visual adaptation of this circuitry is needed to maintain balance during perturbations of self-induced motion. Vestibular and optokinetic (self-motion detection) stimulation is encoded by cerebellar climbing and mossy fibers. These two afferent pathways excite the discharge of Purkinje cells directly. Climbing fibers preferentially decrease the discharge of Purkinje cells by exciting stellate cell inhibitory interneurons. We describe instances adaptive balance at a behavioral level in which prolonged vestibular or optokinetic stimulation evokes reflexive eye movements that persist when the stimulation that initially evoked them stops. Adaptation to prolonged optokinetic stimulation also can be detected at cellular and subcellular levels. The transcription and expression of a neuropeptide, corticotropin releasing factor (CRF), is influenced by optokinetically-evoked olivary discharge and may contribute to optokinetic adaptation. The transcription and expression of microRNAs in floccular Purkinje cells evoked by long-term optokinetic stimulation may provide one of the subcellular mechanisms by which the membrane insertion of the GABAA receptors is regulated. The neurosteroids, estradiol (E2) and dihydrotestosterone (DHT), influence adaptation of vestibular nuclear neurons to electrically-induced potentiation and depression. In each section of this review, we discuss how adaptive changes in the vestibular and optokinetic subsystems of lobule X, inferior olivary nuclei and vestibular nuclei may contribute to the control of balance. [ABSTRACT FROM AUTHOR]

Rationale: Nicotine sensitization involves two functionally distinct phases: induction and expression. Estradiol enhances nicotine sensitization in female rats, but it is not known whether this enhancement is specific to one or both phases. Objectives: We investigated the effects of estradiol selectively during the induction and the expression of nicotine sensitization. Methods: Ovariectomy (OVX) rats were administered E2 during the induction (2 injection days) and/or the expression phase (9 days later) of nicotine sensitization. The selective estrogen receptor modulator tamoxifen (agonist of ERα and ERß, agonist of the g-coupled estradiol receptor GPER1) also was used to elucidate receptor candidates for the effects of E2 on nicotine sensitization. Results: Gonadally intact female rats exhibited expression of nicotine sensitization after a 9-day delay, whereas OVX females did not. Administration of E2 limited to the induction phase of nicotine sensitization rescued expression of nicotine sensitization in OVX females. Tamoxifen during induction did not alter expression of sensitization in gonadally intact female rats, and, like E2, was sufficient to reverse the dampening effects of OVX on expression of sensitization. Conclusions: The enhancing effects of E2 on nicotine sensitization occur during the induction phase of nicotine sensitization, although require a delay to produce the effects on locomotor activity to nicotine, and may involve non-canonical estrogen pathways (e.g., activation of GPER1). [ABSTRACT FROM AUTHOR]

Mounting experimental evidence demonstrate that sex neuroactive steroids (neurosteroids) are essential for memory formation. Neurosteroids have a profound impact on the function and structure of neural circuits and their local synthesis is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and for neural spine formation in different areas of the central nervous system (CNS). Several studies demonstrated that in the hippocampus, 17β-estradiol (E2) is necessary for inducing LTP, while 5α-dihydrotestosterone (DHT) is necessary for inducing LTD. This contribution has been proven by administering sex neurosteroids in rodent models and by using blocking agents of their synthesis or of their specific receptors. The general opposite role of sex neurosteroids in synaptic plasticity appears to be dependent on their different local availability in response to low or high frequency of synaptic stimulation, allowing the induction of bidirectional synaptic plasticity. The relevant contribution of these neurosteroids to synaptic plasticity has also been described in other brain regions involved in memory processes such as motor learning, as in the case of the vestibular nuclei, the cerebellum, and the basal ganglia, or as the emotional circuit of the amygdala. The rapid effects of sex neurosteroids on neural synaptic plasticity need the maintenance of a tonic or phasic local steroid synthesis determined by neural activity but might also be influenced by circulating hormones, age, and gender. To disclose the exact mechanisms how sex neurosteroids participate in finely tuning long-term synaptic changes and spine remodeling, further investigation is required. [ABSTRACT FROM AUTHOR]

An abstract of the article "Fetal epidural hematoma following 'non primary' Cytomegalovirus infection: a case report," by M. Pellegrini, F. D'Antonio, S. Frondaroli, L. Marrone, B. Matarrelli, and C. Celentano is presented.

Neuroactive estrogenic and androgenic steroids influence synaptic transmission, finely modulating synaptic plasticity in several brain regions including the hippocampus. While estrogens facilitate long-term potentiation (LTP), androgens are involved in the induction of long-term depression (LTD) and depotentiation (DP) of synaptic transmission. To examine sex neurosteroid-dependent LTP and LTD in single cells, patch-clamp recordings from hippocampal CA1 pyramidal neurons of male rats and selective antagonists for estrogen receptors (ERs) and androgen (AR) receptors were used. LTP induced by high-frequency stimulation (HFS) depended on activation of ERs since it was prevented by the ER antagonist ICI 182,780 in most of the neurons. Application of the selective antagonists for ERα (MPP) or ERβ (PHTPP) caused a reduction of the LTP amplitude, while these antagonists in combination, prevented LTP completely. LTP was never affected by blocking AR with the specific antagonist flutamide. Conversely, LTD and DP, elicited by low-frequency stimulation (LFS), were impeded by flutamide, but not by ICI 182,780, in most neurons. In few cells, LTD was even reverted to LTP by flutamide. Moreover, the combined application of both ER and AR antagonists completely prevented both LTP and LTD/DP in the same neuron. The current study demonstrates that the activation of ERs is necessary for inducing LTP in hippocampal pyramidal neurons, whereas the activation of ARs is required for LTD and DP. Moreover, both estrogen- and androgen-dependent LTP and LTD can be expressed in the same pyramidal neurons, suggesting that the activation of sex neurosteroids signaling pathways is responsible for bidirectional synaptic plasticity. [ABSTRACT FROM AUTHOR]

Although sex drive is present in many animal species, sexual behavior is not static and, like many other behaviors, can be modified by experience. This modification relies on synaptic plasticity, a sophisticated mechanism through which neurons change how they process a given stimulus, and the neurophysiological basis of learning. This review addresses the main plastic effects of steroid sex hormones in the central nervous system (CNS) and the effects of sexual experience on the CNS, including effects on neurogenesis, intracellular signaling, gene expression, and changes in dendritic spines, as well as behavioral changes. [ABSTRACT FROM AUTHOR]

The brain has long been known as a dimorphic organ and as a target of estrogen. Neurogenesis, including proliferation and differentiation of neural stem cells (NSCs), could be stimulated and regulated by estrogen. However, the dose and timing of estrogen treatment is controversial, and the underlying mechanism remains unclear. In this study, we tested the effects of various estrogen doses on the neurogenesis of NSCs derived from Sprague-Dawley rat embryos. First, we identified that the estrogen receptor-ERa, ERß and GPR30 were highly expressed in NSCs. The results from cell cycle and Western blot analyses revealed that 10 nM 17ß-estradiol (E2) treatment for 3 days significantly increased NSCs proliferation of and p-ERK1/2 expression level but that 50 nM E2 exposure markedly decreased NSCs proliferation and p-ERK1/2 expression level. According to immunofluorescence staining and Western blot analyses, 10 nM E2 treatment for 7 days significantly stimulated NSCs to differentiate into neurons and inhibited their differentiation into astrocytes. These results demonstrate that NSCs are a target of estrogen and that an appropriate dose of E2 (10 nM) can significantly increase the proliferation of NSCs and stimulate NSCs to differentiate into neurons, which contributes to knowledge regarding the regulatory effects of estrogens on neurogenesis. [ABSTRACT FROM AUTHOR]

The modulation of brain function and behavior by steroid hormones was classically associated with their secretion by peripheral endocrine glands. The discovery that the brain expresses the enzyme aromatase, which produces estradiol from testosterone, expanded this traditional concept. One of the best-studied roles of brain estradiol synthesis is the control of reproductive behavior. In addition, there is increasing evidence that estradiol from neural origin is also involved in a variety of non-reproductive functions. These include the regulation of neurogenesis, neuronal development, synaptic transmission, and plasticity in brain regions not directly related with the control of reproduction. Central aromatase is also involved in the modulation of cognition, mood, and non-reproductive behaviors. Furthermore, under pathological conditions aromatase is upregulated in the central nervous system. This upregulation represents a neuroprotective and likely also a reparative response by increasing local estradiol levels in order to maintain the homeostasis of the neural tissue. In this paper, we review the non-reproductive functions of neural aromatase and neural-derived estradiol under physiological and pathological conditions. We also consider the existence of sex differences in the role of the enzyme in both contexts. [ABSTRACT FROM AUTHOR]

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites. [ABSTRACT FROM AUTHOR]

Electrophysiological recordings were used to investigate the role of the local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone ( DHT) on synaptic long-term effects induced in the hippocampal CA1 region of male rat slices. Long-term depression ( LTD) and long-term potentiation ( LTP), induced by different stimulation patterns, were examined under the block of the DHT synthesis by finasteride (FIN), and the E2 synthesis by letrozole (LET). We used low frequency stimulation ( LFS) for LTD, high frequency stimulation ( HFS) for LTP, and intermediate patterns differing in duration or frequency. We found that FIN reverted the LFS- LTD into LTP and enhanced LTP induced by intermediate and HFSs. These effects were abolished by exogenous DHT at concentration higher than the basal one, suggesting a stimulus dependent increase in DHT availability. No effect on the synaptic responses was observed giving DHT alone. Moreover, we found that the inhibition of E2 synthesis influenced the HFS- LTP by reducing its amplitude, and the exogenous E2 either enhanced HFS- LTP or reverted the LFS- LTD into LTP. The equivalence of the E2 concentration for rescuing the full HFS- LTP under LET and reverting the LFS- LTD into LTP suggests an enhancement of the endogenous E2 availability that is specifically driven by the HFS. No effect of FIN or LET was observed on the responses to stimuli that did not induce either LTD or LTP. This study provides evidence that the E2 and DHT availability combined with specific stimulation patterns is determinant for the sign and amplitude of the long-term effects. [ABSTRACT FROM AUTHOR]

The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM inhibitor letrozole reduced spine synapse density in the BL of adult female mice but not in the BL of male mice. Similarly, in organotypic corticoamygdalar slice cultures from immature rats, treatment with letrozole significantly reduced spine synapses in the BL only in cultures derived from females. In addition, letrozole sex-specifically altered synaptic properties in the BL: in acute slices from juvenile (prepubertal) female rats, wash-in of letrozole virtually abolished long-term potentiation (LTP), whereas it did not prevent the generation of LTP in the slices from males. Together, these data indicate that neuron-derived E2 modulates synaptic plasticity in rodent BLA sex-dependently. As protein expression levels of AROM, estrogen and androgen receptors did not differ between males and females and were not sex-specifically altered by letrozole, the findings suggest sex-specific mechanisms of E2 signaling. [ABSTRACT FROM AUTHOR]

Why vestibular compensation (VC) after an acute unilateral vestibular loss is the neuro-otologist's best friend is the question at the heart of this paper. The different plasticity mechanisms underlying VC are first reviewed, and the authors present thereafter the dual concept of vestibulo-centric versus distributed learning processes to explain the compensation of deficits resulting from the static versus dynamic vestibular imbalance. The main challenges for the plastic events occurring in the vestibular nuclei (VN) during a post-lesion critical period are neural protection, structural reorganization and rebalance of VN activity on both sides. Data from animal models show that modulation of the ipsilesional VN activity by the contralateral drive substitutes for the normal push-pull mechanism. On the other hand, sensory and behavioural substitutions are the main mechanisms implicated in the recovery of the dynamic functions. These newly elaborated sensorimotor reorganizations are vicarious idiosyncratic strategies implicating the VN and multisensory brain regions. Imaging studies in unilateral vestibular loss patients show the implication of a large neuronal network (VN, commissural pathways, vestibulo-cerebellum, thalamus, temporoparietal cortex, hippocampus, somatosensory and visual cortical areas). Changes in gray matter volume in these multisensory brain regions are structural changes supporting the sensory substitution mechanisms of VC. Finally, the authors summarize the two ways to improve VC in humans (neuropharmacology and vestibular rehabilitation therapy), and they conclude that VC would follow a 'top-down' strategy in patients with acute vestibular lesions. Future challenges to understand VC are proposed. [ABSTRACT FROM AUTHOR]

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b- estradiol (E2) and 5a-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5a-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas coexposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. [ABSTRACT FROM AUTHOR]

Sex and gender differences have long been a research topic of interest, yet few studies have explored the specific differences in neurological responses between men and women during and after spaceflight. Knowledge in this field is limited due to the significant disproportion of sexes enrolled in the astronaut corps. Research indicates that general neurological and sensory differences exist between the sexes, such as those in laterality of amygdala activity, sensitivity and discrimination in vision processing, and neuronal cell death (apoptosis) pathways. In spaceflight, sex differences may include a higher incidence of entry and space motion sickness and of post-flight vestibular instability in female as opposed to male astronauts who flew on both short- and long-duration missions. Hearing and auditory function in crewmembers shows the expected hearing threshold differences between men and women, in which female astronauts exhibit better hearing thresholds. Longitudinal observations of hearing thresholds for crewmembers yield normal age-related decrements; however, no evidence of sex-related differences from spaceflight has been observed. The impact of sex and gender differences should be studied by making spaceflight accessible and flying more women into space. Only in this way will we know if increasingly longer-duration missions cause significantly different neurophysiological responses in men and women. [ABSTRACT FROM AUTHOR]

Accumulated studies have shown that 17β-estradiol (E2) can be de novo synthesized in the hippocampus, and its role in the regulation of hippocampal synaptic plasticity, which is the basis of learning and memory, has long been exploring. Steroidogenic enzymes (e.g., aromatase) that are essential to the hippocampus-synthesized synthesis of E2 have been detected in the hippocampus. Inhibition of E2 synthesis by aromatase inhibitors significantly reduces the density of hippocampal spine synapses, levels of some synaptic proteins such as spinopholin and synaptophysin. Moreover, the electrophysiological properties of hippocampal neurons are also changed in response to this inhibition. The influences of gonadal and hippocampal E2 on synaptic plasticity may exist some differences, since some reports showed that gonadal (or circulating) estrogens have no obvious effects in the modulation of hippocampal synaptic proteins as evidenced in some ovariectomized animals and postmenopausal women who suffered from Alzheimer's disease (AD). These evidences leads to a hypothesis that hippocampal E2 may play a more important role in modulation of synaptic plasticity than gonadal E2. The signaling pathways, whereby hippocampal E2 modulates synaptic plasticity, insist of classical chronic genomic pathway and rapid nongenomic pathway, which mediated by nonnuclear estrogen receptor (GPER) and/or nuclear or nonnuclear estrogen receptors, which require coactivators for their transcription activity. Among which steroid receptor coactivator-1 (SRC-1) is the predominant coactivator p160 family members in the brain. Several clues have shown that SRC-1 is expressed in hippocampus and is highly correlated with some key synaptic proteins developmentally or after orchidectomy but not ovariectomy, indicating SRC-1 may be regulated by hippocampus-synthesized E2 and profoundly involved in the mediation of hippocampal E2 regulation of hippocampal synaptic plasticity. Further studies about the exact roles of hippocampus-synthesized E2 and therefore SRC-1 are urgently needed in order to facilitate our understanding of hippocampal E2, which will be very important to the development of novel strategies of estrogen replacement therapy against neurodegenerative deficits such as Alzheimer's disease (AD). [ABSTRACT FROM AUTHOR]

Rationale: The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years. Objectives: New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update. Results: Highly specific actions of PregS affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission and the pharmacological effects of PregS on various receptors and ion channels are discussed. The discovery of a high potency (nanomolar) signal transduction pathway for PregS-induced NMDAR trafficking to the cell surface via a Ca- and G protein-coupled receptor (GPCR)-dependent mechanism and a potent (EC ~ 2 pM) direct enhancement of intracellular Ca levels is discussed in terms of its agonist effects on long-term potentiation (LTP) and memory. Lastly, preclinical and clinical studies assessing the promnestic effects of PregS and pregnenolone toward cognitive dysfunction in schizophrenia, and altered serum levels in epilepsy and alcohol dependence, are reviewed. Conclusions: PregS is present in human and rodent brain at physiologically relevant concentrations and meets most of the criteria for an endogenous neurotransmitter/neuromodulator. PregS likely plays a significant role in modulation of glutamatergic excitatory synaptic transmission underlying learning and memory, yet the molecular target(s) for its action awaits identification. [ABSTRACT FROM AUTHOR]

Using a mouse brain slice preparation, we studied the modulatory effects of a feedback projection from higher visual cortical areas, mostly or exclusively area LM (or V2), on two inputs to layer 4 cells in the first visual area (V1). The two inputs to these cells were geniculocortical and an unspecified intracortical input, possibly involving layer 6 cells. We found that activation of metabotropic glutamate receptors (mGluRs) from stimulation of the feedback projection reduced the evoked excitatory postsynaptic currents of both of these inputs to layer 4 but that this modulation acts in an input-specific way. Reducing the strength of the geniculocortical input in adults involved both presynaptic and postsynaptic group I mGluRs (although in younger animals presynaptic group II mGluRs were also involved), whereas modulation of the intracortical input acted entirely via postsynaptic group II mGluRs. These results demonstrate that one of the effects of this feedback pathway is to control the gain of geniculocortical transmission. [ABSTRACT FROM AUTHOR]

Phenol red is widely used in cell culture as a pH indicator. Recently, it also has been reported to have estrogen-like bioactivity and be capable of promoting cell proliferation in different cell lines. However, the effect of phenol red on primary neuronal culture has never been investigated. By using patch clamp technique, we demonstrated that hippocampal pyramidal neurons cultured in neurobasal medium containing no phenol red had large depolarization-associated epileptiform bursting activities, which were rarely seen in neurons cultured in phenol red-containing medium. Further experiment data indicate that the suppressive effect of the phenol red on the abnormal epileptiform burst neuronal activities was U-shape dose related, with the most effective concentration at 28 µM. In addition, this concentration related inhibitory effect of phenol red on the epileptiform neuronal discharges was mimicked by 17-β-estradiol, an estrogen receptor agonist, and inhibited by ICI-182,780, an estrogen receptor antagonist. Our results suggest that estrogen receptor activation by phenol red in the culture medium prevents formation of abnormal, epileptiform burst activity. These studies highlight the importance of phenol red as estrogen receptor stimulator and cautions of careful use of phenol red in cell culture media. [ABSTRACT FROM AUTHOR]

Equilibrium of the body is the result of perfect control of the relationship between the body and the environment in every life condition. Equilibrium is an essential function and hence cannot be entrusted to a single organ or apparatus. The function requires an entire balance system consisting of a set of communicating structures and processes. At every moment, the central nervous system (CNS) processes the inputs received from various receptors in the human body. Key steps in processing the different inputs involve recognition of the single afferences, comparison and integration of the multitude of afferences and their modulation to regulate the gain on the whole system. Furthermore, the CNS stores the experiences and finally programmes the responses to adapt to the ongoing reality. The vestibular system plays a critical role in maintaining the balance function and, therefore, its inputs must be integrated with the highest brain functions. From an anatomo-physiological perspective, the existence of cognitive-vestibular interaction is supported by the presence of neuronal projections between the vestibular centres in the brainstem and both the cerebral and cerebellar cortex. However, the vestibular system is connected to the whole CNS. In humans, galvanic and caloric vestibular stimulation activates several cortical regions. The so-called vestibular cortex is a multisensorial cortex because it receives not only vestibular inputs but also somatosensory and visual inputs. The vestibular system is tightly connected to the limbic system, which regulates emotions, homeostasis and storage of experiences. More specifically, the vestibular inputs are basic to the topokinetic memory of the hippocampus. Acute lesions affecting the peripheral receptors or nerves produce a sudden change in information reaching the balance system, which results in serious symptoms. Hence, all balance disorders lead to a significant degree of handicap and emotional disturbance for the patient. The evolution of vestibular symptoms is related to the ability of the CNS to adapt to the development of new and dangerous conditions. The plasticity of the CNS permits adaptation to both physiological and pathological conditions in every condition of life. Cognitive resources play a continuous role in the reorganization of the balance function during adaptation to vestibular loss. Despite the fact that the adaptation is usually satisfactory, a 'vestibular cicatrix' remains forever. The vestibular cicatrix is characterized by topokinetic memory disorganization at a high level of information processing, spatial working memory deficit, alerting state with abnormal levels of anxiety and depression, substitutional saccadic eye movements if the head is turned quickly in the direction of the damaged ear, errors in cognitive tasks and fewer attentional resources. Vestibular adaptation is not constant in time and is dependent on many individual factors (e.g. age, gender, emotions, stress). Vertigo has a negative impact on the quality of life, affects everyday activities and is associated with cognitive impairment. Hence, treatment of vertigo assumes great significance. Treatment must target the entire CNS and should aim to facilitate the vestibular adaptation process. It is preferred that the patient is not confined to bed after the first two days in order to allow the early initiation of dynamic experiences, which are vital for adaptation without running the risk of activating the mechanism of fear and traumatic memory. While selecting a drug for therapy, the plastic and cognitive neuronal mechanisms activated by vestibular deficits must be taken into account. If the use of symptomatic drugs in the past was simply a kind of 'siesta strategy', it is expected that in future we will rely on a more dynamic strategy, a 'mind-energy strategy', i.e. a vertigo treatment that would also involve a cognitive approach. Adaptation mechanisms require activation of neurons, synapses and neuronal metabolism, particularly in mitochondria. Thus, we need drugs that enhance neuronal metabolic activity, neurotransmission and facilitate the transfer of information between the two hemispheres. It may be particularly useful to counsel patients about the disease and its likely consequences. An excessive alerting state can be prevented by providing patients (and their families) with a simple but detailed explanation of how symptoms are provoked and about the process of adaptation following a balance disorder. In the first days following the vertigo attack, the new dynamic experiences are fundamental for the patients, who need to stay active instead of totally passive. For these patients, the use of sedative drugs should be limited, while the use of nootropic and/or neuromodulator drugs and possibly anti-anxiety drugs in anxious or stressed subjects should be continued. If symptoms persist, factors that interact with the processes of adaptation should be identified and limited, thus reducing stress. The other sensory problems that affect the visual or proprioceptive apparatus should be removed and should have vicarious compensatory activity. Possibilites of reducing the high levels of anxiety, depression and psychological conditions that interact negatively should be considered. The use of nootropics and/or neuromodulator drugs should be continued and a customized rehabilitation training should be implemented. [ABSTRACT FROM AUTHOR]

Elevated levels of stress and anxiety often accompany vestibular dysfunction, while conversely complaints of dizziness and loss of balance are common in patients with panic and other anxiety disorders. The interactions between stress and vestibular function have been investigated both in animal models and in clinical studies. Evidence from animal studies indicates that vestibular symptoms are effective in activating the stress axis, and that the acute stress response is important in promoting compensatory synaptic and neuronal plasticity in the vestibular system and cerebellum. The role of stress in human vestibular disorders is complex, and definitive evidence is lacking. This article reviews the evidence from animal and clinical studies with a focus on the effects of stress on the central vestibular pathways and their role in the pathogenesis and management of human vestibular disorders. [ABSTRACT FROM AUTHOR]

Summary 1. 17-β-oestradiol (E2) plays a critical role in neuroprotection through both genomic and non-genomic mechanisms. The aim of the present study was to investigate the role of G-protein-coupled receptor 30 (GPR30), a new kind of oestrogen receptor, in the neuroprotection against oxidative insult. 2. The neuroprotection evoked by GPR30 stimulation was examined in cultured cortical neurons. Hoechst 33258/propidium iodide double staining, flow cytometric analysis and western blotting were applied to assess neuronal apoptosis induced by H2O2. 3. We found that the GPR30 agonist, G1, and E2 attenuated apoptosis induced by H2O2 exposure. Furthermore, G1 (1 nmol/L) or E2 (1 nmol/L) significantly increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bcl-2 and pro-caspase-3. Pretreatment with ICI182780, a highly selective nuclear oestrogen receptor antagonist that is used to block the classical ERα and ERβ receptors, did not totally block the neuroprotective effects of E2 (1 nmol/L) and had no effect on the neuroprotective effects of G1 (1 nmol/L). 4. Our data suggest that GPR30 is involved in the neuroprotection against oxidative insult. The neuroprotection evoked by GPR30 stimulation was associated with the signalling through the ERK1/2 kinase pathway. In addition, the anti-apoptotic activity of GPR30 was dependent on the expression of Bcl-2 and pro-caspase-3. GPR30 might be a potential therapeutic target for neuroprotection and oxidative stress. [ABSTRACT FROM AUTHOR]

Many biologically active neurosteroids, including dehydroepiandrosterone (DHEA), are synthesised in the brain. DHEA is a potent endogenous modulator of several neuronal functions, and alterations of DHEA are correlated with various neurobiological deficits. The cytochrome P450 17α-hydroxylase/C(17,20)-lyase (P450C) plays a pivotal role in the synthesis of DHEA from pregnenolone and progesterone. We investigated the immunohistochemical localisation and molecular expression of P450C in the superior, lateral, medial and inferior vestibular nuclei (VCN) of adult male rats by western blotting and indirect immunofluorescence analysis. Immunoreactive P450C was widely distributed in all VCN and the expression of P450C was confirmed by western blot analysis. The present study demonstrates, for the first time, the presence and anatomical distribution of P450C in the VCN. Given that neurosteroids can modulate neuronal activities in the medial vestibular nucleus, DHEA synthesised in the VCN may play an important role in the control of specific activities at this level. [ABSTRACT FROM AUTHOR]

Head/body motion-related sensory signals are transformed in second-order vestibular neurons (2°VN) into commands for appropriate motor reactions that stabilize gaze and posture during locomotion. In all vertebrates, these neurons form functional subgroups with different membrane properties and response dynamics, compatible with the necessity to process a wide range of motion-related sensory signals. In frog, 2°VN subdivide into two well-defined populations with distinctly different intrinsic membrane properties, discharge dynamics and synaptic response characteristics. Tonic 2°VN form low-pass filters with membrane properties that cause synaptic amplification, whereas phasic 2°VN form band-pass filters that cause shunting of repetitive inputs. The different, yet complementary, filter properties render tonic neurons suitable for integration and phasic neurons for differentiation and event detection. Specific insertion of phasic 2°VN into local vestibular networks of inhibitory interneurons reinforces the functional consequences of the intrinsic membrane properties of this particular cell type with respect to the processing of afferent sensory signals. Thus, the combination of matching intrinsic cellular and emerging network properties generates sets of neuronal elements that form adjustable, frequency-tuned filter components for separate transformation of the various dynamic aspects of head motion-related signals. The overall frequency tuning of central vestibular neurons differs between vertebrates along with variations in species-specific locomotor dynamics, thereby illustrating an ecophysiological plasticity of the involved neuronal elements. Moreover, separation into multiple, dynamically different subtypes at any neuronal level along the vestibulo-motor reflex pathways suggests an organization of head motion-related sensory-motor transformation in parallel, frequency-tuned channels. [ABSTRACT FROM AUTHOR]

Numerous studies in rodents have shown that the functional efficacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modified during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deficient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modifications in the distribution of these neurons into different neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and finally, (3) the intracellular calcium concentration has a major effect on the intrinsic membrane properties of central vestibular neurons. [ABSTRACT FROM AUTHOR]

Conclusion: The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17ββ-estradiol (cE2). Objective: The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE2 influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E2 (nE2) from testosterone (T). Methods: We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE2. Selective blocking agents of converting T enzymes were used. Results: Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E2, and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated a chronic neurosteroid-dependent inhibition of activity-dependent spinal reflex potentiation (SRP), but it remains unclear whether neurosteroids acutely modulate SRP induction. This study shows progesterone as well as two of its 3α,5α-derivatives, allopregnalonone and 3α5α-tetrahydrodeoxycorticosterone (THDOC), to be capable of producing acute GABAA receptor (GABAAR)-dependent inhibition of SRP. When compared with test simulation (1 stimulation/30 s) of pelvic afferent nerves that evoked a baseline reflex activity in an external urethra sphincter electromyogram, repetitive stimulation (RS; 1 stimulation/1 s) induced SRP characterized by an increase in the evoked activity. Intrathecal progesterone (3-30 µM, 10 µl) at 10 rain before stimulation onset dose dependently prevented RS induction. Intrathecal allopregnalonone (10 µM, 10 µl it) and THDOC (10 µM, 10 µl it) also prevented the SRP caused by RS. Pretreatment with the GABAAR antagonist bicuculline (10 µM, 10 µl it) at 1 min before progesterone/neurosteroid injection attenuated the inhibition of SRP caused by progesterone, allopregnanolone, and THDOC. Results suggest that progesterone and its neurosteroid metabolites may be crucial to the development of pelvic visceral neuropathic/postinflammatory pain and imply clinical use of neurosteroids, such as allopregnanolone and THDOC, for visceral pain treatment. [ABSTRACT FROM AUTHOR]

Besides their genomic effects, oestrogens, 17β-oestradiol in particular, also activate cellular effects that may be too rapid (seconds to minutes) to result from de novo protein synthesis. Although the existence of such nongenomic actions has been extensively demonstrated in vitro, the understanding of their behavioural significance is only emerging. Recent findings provide evidence that acute oestrogen treatments significantly affect a variety of behavioural processes, including sexual behaviour, social communication and cognition. One question arising from these results concerns the source of the oestrogens mediating nongenomic effects in vivo. In this review, data collected in vitro and in vivo are presented supporting the notion that fast modulations of local testosterone aromatisation can rapidly control the local oestrogen concentration in a time frame compatible with their rapid actions. Taken together, these data provide compelling evidence of how rapid changes in the local production and action of oestrogens can shape complex behaviours. [ABSTRACT FROM AUTHOR]

The article discusses the plastic events in the bilateral vestibular nuclei (VN) complexes after unilateral labyrinthectomy (UL) and unilateral vestibular neurectomy (UVN). It notes that VN in the brain stem is capable of being experimentally deafferented by lesioning the peripheral sensor receptors. It states that plastic events in VN after unilateral vestibular loss involve second-order vestibular neurons that cannot be restricted to neuronal populations.

Background: A complete explanation of the mechanisms by which Pb2+ exerts toxic effects on developmental central nervous system remains unknown. Glutamate is critical to the developing brain through various subtypes of ionotropic or metabotropic glutamate receptors (mGluRs). Ionotropic Nmethyl- D-aspartate receptors have been considered as a principal target in lead-induced neurotoxicity. The relationship between mGluR3/mGluR7 and synaptic plasticity had been verified by many recent studies. The present study aimed to examine the role of mGluR3/mGluR7 in lead-induced neurotoxicity. Methods: Twenty-four adult and female rats were randomly selected and placed on control or 0.2% lead acetate during gestation and lactation. Blood lead and hippocampal lead levels of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. Impairments of short -term memory and long-term memory of pups were assessed by tests using Morris water maze and by detection of hippocampal ultrastructural alterations on electron microscopy. The impact of lead exposure on mGluR3 and mGluR7 mRNA expression in hippocampal tissue of pups were investigated by quantitative real-time polymerase chain reaction and its potential role in lead neurotoxicity were discussed. Results: Lead levels of blood and hippocampi in the lead-exposed rats were significantly higher than those in the controls (P < 0.001). In tests using Morris Water Maze, the overall decrease in goal latency and swimming distance was taken to indicate that controls had shorter latencies and distance than leadexposed rats (P = 0.001 and P < 0.001 by repeated-measures analysis of variance). On transmission electron microscopy neuronal ultrastructural alterations were observed and the results of real-time polymerase chain reaction showed that exposure to 0.2% lead acetate did not substantially change gene expression of mGluR3 and mGluR7 mRNA compared with controls. Conclusion: Exposure to lead before and after birth can damage short-term and long-term memory ability of young rats and hippocampal ultrastructure. However, the current study does not provide evidence that the expression of rat hippocampal mGluR3 and mGluR7 can be altered by systemic administration of lead during gestation and lactation, which are informative for the field of lead-induced developmental neurotoxicity noting that it seems not to be worthwhile to include mGluR3 and mGluR7 in future studies. [ABSTRACT FROM AUTHOR]

We investigated the maturation profile of subunits of ionotropic glutamate receptors in vestibular nuclear neurons that were activated by sinusoidal linear acceleration along the vertical plane. The otolithic origin of Fos expression in these neurons was confirmed as a marker of functional activation when labyrinthectomized and/or stationary control rats contrasted by showing sporadically scattered Fos-labeled neurons in the vestibular nuclei. By double immunohistochemistry for Fos and one of the receptor subunits, otolith-related neurons that expressed either α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate or N-methyl-d-aspartate subunits were first identified in the medial vestibular nucleus, spinal vestibular nucleus and Group x by postnatal day (P)7, and in the lateral vestibular nucleus and Group y by P9. No double-labeled neurons were found in the superior vestibular nucleus. Within each vestibular subnucleus, these double-labeled neurons constituted ∼90% of the total Fos-labeled neurons. The percentage of Fos-labeled neurons expressing the GluR1 or NR2A subunit showed developmental invariance in all subnuclei. For Fos-labeled neurons expressing the NR1 subunit, similar invariance was observed except that, in Group y, these neurons decreased from P14 onwards. For Fos-labeled neurons expressing the GluR2, GluR2/3, GluR4 or NR2B subunit, a significant decrease was found by the adult stage. In particular, those expressing the GluR4 subunit showed a two- to threefold decrease in the medial vestibular nucleus, spinal vestibular nucleus and Group y. Also, those expressing the NR2B subunit showed a twofold decrease in Group y. Taken together, the postsynaptic expression of ionotropic glutamate receptor subunits in different vestibular subnuclei suggests that glutamatergic transmission within subregions plays differential developmental roles in the coding of gravity-related vertical spatial information. [ABSTRACT FROM AUTHOR]

Although metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 are often found to have similar functions, there is considerable evidence that the two receptors also serve distinct functions in neurons. In hippocampal area CA1, mGluR5 has been most strongly implicated in long-term synaptic depression (LTD), whereas mGluR1 has been thought to have little or no role. Here we show that simultaneous pharmacological blockade of mGluR1 and mGluR5 is required to block induction of LTD by the group 1 mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG). Blockade of mGluR1 or mGluR5 alone has no effect on LTD induction, suggesting that activation of either receptor can fully induce LTD. Consistent with this conclusion, mGluR1 and mGluR5 both contribute to activation of extracellular signal-regulated kinase (ERK), which has previously been shown to be required for LTD induction. In contrast, selective blockade of mGluR1, but not mGluR5, reduces the expression of LTD and the associated decreases in AMPA surface expression. LTD is also reduced in mGluR1 knockout mice confirming the involvement of mGluR1. This shows a novel role for mGluR1 in long-term synaptic plasticity in CA1 pyramidal neurons. In contrast to DHPG-induced LTD, synaptically induced LTD with paired-pulse low-frequency stimulation persists in the pharmacological blockade of group 1 mGluRs and in mGluR1 or mGluR5 knockout mice. This suggests different receptors and/or upstream mechanisms for chemically and synaptically induced LTD. [ABSTRACT FROM AUTHOR]

The last decade has witnessed advances in understanding the roles of receptors of neurotrophin and glutamate in the vestibular system. In the first section of this review, the biological actions of neurotrophins and their receptors in the peripheral and central vestibular systems are summarized. Emphasis will be placed on the roles of neurotrophins in developmental plasticity and in the maintenance of vestibular function in the adult animal. This is reviewed in relation to the developmental expression pattern of neurotrophins and their receptors within the vestibular nuclei. The second part is focused on the functional role of different glutamate receptors on central vestibular neurons. The developmental expression pattern of glutamate receptor subunits within the vestibular nuclei is reviewed in relation to the potential role of glutamate receptors in regulating the development of vestibular function.Copyright © 2003 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]