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Research on glutamatergic neurotransmission has focused mainly on the function of presynaptic and postsynaptic neurons, leaving astrocytes with a secondary role only to ensure successful neurotransmission. However, recent evidence indicates that astrocytes contribute actively and even regulate neuronal transmission at different levels. This review establishes a framework by comparing glutamatergic components between neurons and astrocytes to examine how astrocytes modulate or otherwise influence neuronal transmission. We have included the most recent findings about the role of astrocytes in neurotransmission, allowing us to understand the complex network of neuron-astrocyte interactions. However, despite the knowledge of synaptic modulation by astrocytes, their contribution to specific physiological and pathological conditions remains to be elucidated. A full understanding of the astrocyte’s role in neuronal processing could open fruitful new frontiers in the development of therapeutic applications.

Resumen: se presenta en esta sección una revisión de los artículos científicos de mayor impacto publicados entre febrero de 2022 y mayo del 2022 en las revistas internacionales sobre Sexología con mayor reconocimiento a nivel nacional e internacional (Journal of Sexual Medicine; International Journal of Sexual Health; Archives of Sexual Behavior; Sex roles; Sexual Addiction & Compulsivity, Psychology and Sexuality; Culture, Health and Sexuality; DeSexología, Psicología de la orientación sexual y la diversidad, American Journal of Sexual Education, Journal of Sex & Marital Therapy y Violence Against Woman).

Summary: The laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. Here, we identify critical roles for the autism risk gene Foxp1 in maintaining aRG identity and gating the temporal competency for deep-layer neurogenesis. Early in development, aRG express high levels of Foxp1 mRNA and protein, which promote self-renewing cell divisions and deep-layer neuron production. Foxp1 levels subsequently decline during the transition to superficial-layer neurogenesis. Sustained Foxp1 expression impedes this transition, preserving a population of cells with aRG identity throughout development and extending the early neurogenic period into postnatal life. FOXP1 expression is further associated with the initial formation and expansion of basal RG (bRG) during human corticogenesis and can promote the formation of cells exhibiting characteristics of bRG when misexpressed in the mouse cortex. Together, these findings reveal broad functions for Foxp1 in cortical neurogenesis. : Neocortical progenitors generate distinct cell types in a temporal sequence, yet the mechanisms controlling this process are unclear. Pearson et al. show that the autism risk gene Foxp1 contributes by maintaining apical radial glia character and promoting deep-layer neurogenesis. The association of FOXP1 with human corticogenesis is also investigated. Keywords: brain development, cerebral cortex, neurogenesis, neural stem cell, neural progenitor, neural differentiation, cell fate, Foxp1, transcriptional regulation, autism spectrum disorder

The study assesses how an educational intervention describing uncertainty in child sexual abuse assessments affects estimates of sexual abuse probability by non-physician child abuse professionals (CAP). It evaluates whether CAP incorporate medical information into abuse estimates in concordance with Bayes' Theorem. Eighty-nine CAP estimated the abuse probability for a hypothetical preadolescent female: (1) randomly selected; (2) disclosing abuse; (3) with physical evidence of abuse; and (4) disclosing abuse but with a normal physical examination. CAP then attended a workshop that included discussion of uncertainty in abuse assessment. Post-lecture questionnaire, identical to pre-lecture questionnaires except for estimates of the examination sensitivity and specificity, were administered. Expected responses for post-lecture Scenarios (3) and (4) were generated using Bayes' Theorem and compared to actual responses. Respondents estimated a high abuse prevalence (average 32%, range 5 to 75%). Respondents incorporated medical information into their estimates in a Bayesian manner. However, they undervalued the medical exam findings relative to Bayes' Theorem. These findings suggest CAP had difficulty adjusting for medical uncertainty. Further research into approaches for more easily adopting Bayesian approaches to child abuse decisions may improve the quality of decisions made by child abuse professionals. [ABSTRACT FROM AUTHOR]

Stereotypic cell migrations in the developing brain are fundamental for the proper patterning of brain regions and formation of neural networks. In this work, we uncovered in the developing rat, a population of neurons expressing tyrosine hydroxylase (TH) that migrates posteriorly from the alar plate of the midbrain, in neurophilic interaction with axons of the mesencephalic nucleus of the trigeminal nerve. A fraction of this population was also shown to traverse the mid-hindbrain boundary, reaching the vicinity of the locus coeruleus (LC) in rhombomere 1 (r1). This migratory population, however, does not have a noradrenergic (NA) phenotype and, in keeping with its midbrain origin, expresses Otx2 which is down regulated upon migration into the hindbrain. The interaction with the trigeminal mesencephalic axons is necessary for the arrangement and distribution of migratory cells as these aspects are dramatically altered in whole embryo cultures upon disruption of trigeminal axon projection by interfering with DCC function. Moreover, in mouse embryos in an equivalent developmental stage, we detected a cell population that also migrates caudally within the midbrain apposed to mesencephalic trigeminal axons but that does not express TH; a fraction of this population expresses calbindin instead. Overall, our work identified TH-expressing neurons from the rat midbrain alar plate that migrate tangentially over long distances within the midbrain and into the hindbrain by means of a close interaction with trigeminal mesencephalic axons. A different migratory population in this region and also in mouse embryos revealed diversity among the cells that follow this descending migratory pathway.

Early telencephalic development involves the migration of diverse cell types that can be identified by specific molecular markers. Most prominent among them are Cajal-Retzius (CR) cells that emanate mainly from the cortical hem and to a lesser extent from rostrolateral, septal and caudo-medial regions. One additional territory proposed to give rise to CR cells that migrate dorsally into the neocortex lies at the ventral pallium, although contradictory results question this notion. With the use of a cell-permeable fluorescent tracer in cultured embryos, we identified novel migratory paths of putative CR cells and other populations that originate from the rostrolateral telencephalon at its olfactory region. Moreover, extensive labeling on the lateral telencephalon along its rostro-caudal extent failed to reveal a dorsally-migrating CR cell population from the ventral pallium at the stages analyzed. Hence, this work reveals a novel olfactory CR cell migration and supports the idea that the ventral pallium, where diverse types of neurons converge, does not actually generate CR cells.

The steady state dynamics and experience-dependent plasticity of dendritic spines of layer (L) 2/3 and L5B cortical pyramidal neurons have recently been assessed using in vivo two-photon microscopy (Trachtenberg et al., 2002; Zuo et al., 2005; Holtmaat et al., 2006). In contrast, not much is known about spine dynamics in L4/5a neurons, regarded as direct recipients of thalamocortical input (Constantinople and Bruno, 2013). In the adult mouse somatosensory cortex (SCx), the transcription factor Ebf2 is enriched in excitatory neurons of L4/5a, including pyramidal neurons. We assessed the molecular and electrophysiological properties of these neurons as well as the morphology of their apical tufts (Scholl analysis) and cortical outputs (optogenetics) within the SCx. To test the hypothesis that L4/5a pyramidal neurons play an important role in sensory processing (given their key laminar position; soma depth ~450-480 µm), we successfully labeled them in Ebf2-Cre mice with EGFP by expressing recombinant rAAV vectors in utero. Using longitudinal in vivo two-photon microscopy through a craniotomy (Mostany and Portera-Cailliau, 2008), we repeatedly imaged spines in apical dendritic tufts of L4/5a neurons under basal conditions and after sensory deprivation. Under steady-state conditions in adults, the morphology of the apical tufts and the mean spine density were stable at 0.39 ± 0.05 spines/μm (comparable to L5B, Mostany et al., 2011). Interestingly, spine elimination increases 4-8 days after sensory deprivation, probably due to input loss. This suggests that Ebf2+ L4/5a neurons could be involved in early steps of processing of thalamocortical information.

Polycythemia (venous hematocrit >65%) is rare in healthy newborns (incidence: 0.4%-5%), with serious outcomes (stroke, bowel ischemia) of unknown incidence in asymptomatic infants. No national guidelines address screening or management of asymptomatic infants with polycythemia. Our nursery screened "high risk" (HR) newborns (small for gestational age, large for gestational age, twin, infant of diabetic mother) with poor adherence and low yield. We aimed to decrease polycythemia screening of asymptomatic HR infants by 80% within 6 months., Methods: We conducted an improvement project at a tertiary children's hospital using the Model for Improvement. Eligible infants had an HR ICD-10 code on their problem list, were asymptomatic, over 35 weeks gestational age, and remained in the nursery for >6 hrs. Interventions included discontinuation of prior protocol, education for staff, bimonthly feedback on project performance, and visual reminders. Our primary outcome measure was the proportion of asymptomatic infants who received a hematocrit screen. Secondary measures were screening costs. Balancing measures were the length of stay, detected/symptomatic polycythemia, transfers to ICU/wards, and readmissions within 1 week of discharge., Results: The Nursery unit screened 80% of HR infants at baseline. This decreased to 7.3% after PDSA1, 0% after PDSA2, and 1% after PDSA3. There was no symptomatic polycythemia or statistically significant increase in readmissions/transfers. One month of monitoring revealed persistent changes., Conclusion: Simple quality improvement interventions such as education, reminders, and feedback can facilitate the deimplementation of low-value practices., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Emotional stress, through elevating corticosterone (CORT) levels may reduce feeding in rodents however when offered palatable food, stressed animals ingest more food compared to non-stressed controls. Nucleus accumbens (NAc) is part of the mesocorticolimbic system and participates in processing rewarding characteristics of food modulating palatable food intake, mainly when glucocorticoids are elevated. A possible mediator of CORT effects is accumbal thyrotropin-releasing hormone (TRH), which reduces chow intake in rats when administered into the NAc. We aimed to study the TRH role in hedonic feeding in stressed rats. For 14 days, animals with ad libitum access to chow or chow plus chocolate milk were either group-housed or singly-housed to induce stress. Rats with access to chocolate milk showed hyperphagia and decreased accumbal TRH mRNA levels, which were potentiated by stress. Results suggest that TRH downregulation was permissive of the increased palatable food intake. TRH injections into NAc of singly-housed animals with palatable food access reduced their food intake and increased serum CORT levels. The accumbal injections of a glucocorticoid receptor antagonist (mifepristone) in stressed rats with palatable food access, reduced only palatable food intake and increased accumbal TRH expression and serum CORT levels. This modulation of TRH mRNA when CORT signaling is modified suggests that accumbal TRH is downstream of glucocorticoids activity, which specifically increase palatable food intake. Our results strengthen the TRH involvement in regulating emotional aspects of hedonic feeding in stressed animals. Finding new therapies directed towards increasing TRHergic activity in NAc may be protective against overeating.

Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants considered as neurotoxicants and endocrine disruptors with important biological effects ranging from alterations in growth, reproduction, and effects on the hypothalamus-pituitary-adrenal axis. The vasopressinergic (AVPergic) system is a known target for pentaBDEs mixture (DE-71) and the structurally similar chemicals, polychlorinated biphenyls. However, the potential adverse effects of mixtures containing octaBDE compounds, like DE-79, on the AVPergic system are still unknown. The present study aims to examine the effects of perinatal DE-79 exposure on the AVPergic system. Dams were dosed from gestational day 6 to postnatal day 21 at doses of 0 (control), 1.7 (low) or 10.2 (high) mg/kg/day, and male offspring from all doses at 3-months-old were subjected to normosmotic and hyperosmotic challenge. Male offspring where later assessed for alterations in osmoregulation (i.e. serum osmolality and systemic vasopressin release), and both vasopressin immunoreactivity (AVP-IR) and gene expression in the hypothalamic paraventricular and supraoptic nuclei. Additionally, to elucidate a possible mechanism for the effects of DE-79 on the AVPergic system, both neuronal nitric oxide synthase immunoreactivity (nNOS-IR) and mRNA expression were investigated in the same hypothalamic nuclei. The results showed that perinatal DE-79 exposure AVP-IR, mRNA expression and systemic release in adulthood under normosmotic conditions and more evidently under hyperosmotic stimulation. nNOS-IR and mRNA expression were also affected in the same nuclei. Since NO is an AVP regulator, we propose that disturbances in NO could be a mechanism underlying the AVPergic system disruption following perinatal DE-79 exposure leading to osmoregulation deficits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Early-life overfeeding (OF) disrupts neuroendocrine systems, energy homeostasis and food intake regulation inducing overeating and overweight in adults. Adult rats raised in small litters during lactation, display hyperphagia and overweight since weaning and exhibit a decrease in thyrotropin-releasing hormone (TRH) mRNA expression in hypothalamic paraventricular nucleus (PVN). This is counterintuitive because TRH expression should increase to activate the hypothalamic-pituitary-thyroid (HPT) axis and promote energy expenditure, thus, HPT axis seems inhibited in OF rats. Leptin, an adipocyte-synthesized hormone that stimulates hypothalamic TRH expression, enhances both TRH anorectic effects and HPT axis-induced metabolic rate. To evaluate hypothalamic resistance to the anorectic and HPT axis stimulatory actions of leptin, we injected leptin i.p. to ad libitum fed and to 48-h fasted adult control (reared in normal litters) and to small-litter reared (OF) male Wistar rats. Findings showed that HPT axis was still responsive to leptin, since PVN TRH mRNA levels, median eminence TRH release and T 4 serum concentration increased in both, ad libitum and fasted OF rats after leptin administrations. Leptin was ineffective to reduce feeding of OF animals. By comparing leptin receptor (ObRb) expression changes between arcuate and PVN nuclei, we observed that arcuate ObRb was not modified in response to leptin administrations in OF rats, likely accounting for the differential effects in feeding and HPT axis function. Nevertheless, ObRb expression was modified by leptin in the PVN of OF rats to the same extent as controls; this supports the hormone's role as a therapeutic agent for early onset obesity in adults., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Early-life stress induces endocrine and metabolic alterations that increase food intake and overweight in adulthood. The stress response activates the corticotropin-releasing hormone (CRH) and urocortins' (Ucns) system in the hypothalamic paraventricular nucleus (PVN). These peptides induce anorexic effects through CRH-R2 receptor activation; however, chronic stressed animals develop hyperphagia despite of high PVN CRH expression. We analyzed this paradoxical behavior in adult rats subjected to maternal separation (MS) for 180min/daily during post-natal days 2-14, evaluating their body weight gain, food intake, serum corticosterone and vasopressin concentrations, PVN mRNA expression of CRH-R1, CRH-R2, CRH, Ucn2, Ucn3, vasopressin and CRH-R2 protein levels. MS adults increased their feeding, weight gain as well as circulating corticosterone and vasopressin levels, evincing chronic hyperactivity of the stress system. MS induced higher PVN CRH, Ucn2 and CRH-R2 mRNA expression and protein levels of CRH-R2 showed a tendency to decrease in the cellular membrane fraction. An intra-PVN injection of the CRH-R2 antagonist antisauvagine-30 in control adults increased receptor's mRNA expression, mimicking the observed PVN receptor's up-regulation of early-life MS adults. An injection of Ucn-2 directly into the PVN reduced food intake and increased PVN pCREB/CREB ratio in control animals; in contrast, Ucn-2 was unable to reduce food intake and enhance phosphorylated-CREB levels in PVN of MS rats. In conclusion, the chronic hyperactivity of the stress axis and PVN CRH-R2 resistance to Ucn2 effects, supported impaired receptor functionality in MS animals, probably due to its chronic stimulation by CRH or Ucn2, induced by early-life stress., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thyrotropin-releasing hormone (TRH) has anorexigenic and anxiolytic functions when injected intraventricularly. Nucleus accumbens (NAcc) is a possible brain region involved, since it expresses proTRH. TRH from hypothalamic paraventricular nucleus (PVN) has a food intake-regulating role. TRHergic pathways of NAcc and PVN are implicated in anxiety and feeding. Both behaviors depend on cAMP and phosphorylated-cAMP response element binding protein (pCREB) intracellular levels. Intracellular levels of cAMP are controlled by the degrading activity of phosphodiesterases (PDEs). Since TRH transcription is activated by pCREB, a specific inhibitor of PDE7B may regulate TRH-induced effects on anxiety and feeding. We evaluated the effectiveness of an intra-accumbal and intraperitoneal (i.p.) administration of a PDE7 inhibitor (BRL-50481) on rats' anxiety-like behavior and food intake; also on TRH mRNA and protein expression in NAcc and PVN to define its mediating role on the PDE7 inhibitor-induced behavioral changes. Accumbal injection of 4μg/0.3μL of PDE7 inhibitor decreased rats' anxiety. The i.p. injection of 0.2mg/kg of the inhibitor was able to increase the PVN TRH mRNA expression and to decrease feeding but did not change animals' anxiety levels; in contrast, 2mg/kg b.w inhibitor enhanced accumbal TRH mRNA, induced anxiolysis with no change in food intake. PDE7 inhibitor induced anxiolytic and anorexigenic like behavior depending on the dose used. Results supported hypothalamic TRH mediated feeding-reduction effects, and accumbal TRH mediation of inhibitor-induced anxiolysis. Thus, an i.p dose of this inhibitor might be reducing anxiety with no change in feeding, which could be useful for obese patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

The neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor are members of the endogenous opioid peptide family. In mammals N/OFQ modulates a variety of biological functions such as nociception, food intake, endocrine, control of neurotransmitter release, among others. In the molluscs Cepea nemoralis and Helix aspersa the administration of N/OFQ produces a thermopronociceptive effect. However, little is known about its existence and anatomic distribution in invertebrates. The aim of this study was to provide a detailed anatomical distribution of N/OFQ like peptide immunoreactivity (N/OFQ-IL), to quantify the tissue content of this peptide, as well as to demostrate molecular evidence of N/OFQ mRNA in the nervous tissue of periesophageal ganglia of the land snail H. aspersa. Immunohistochemical, immunocytochemical, radioimmunoanalysis (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) techniques were used. With regard to RT-PCR, the primers to detect expression of mRNA transcripts from H. aspersa were derived from the rat N/OFQ opioid peptide. We show a wide distribution of N/OFQ-IL in neurons and fibers in all perioesophageal ganglia, fibers of the neuropile, nerves, periganglionar connective tissue, aortic wall and neurohemal sinuses. The total amount of N/OFQ-IL in the perioesophageal ganglia (7.75 ± 1.75 pmol/g of tissue) quantified by RIA was similar to that found in mouse hypothalamus (10.1 ± 1.6 pmol/g of tissue). In this study, we present molecular evidence of N/OFQ mRNA expression. Some N/OFQ-IL neurons have been identified as neuroendocrine or involved in olfaction, hydro-electrolyte regulation, feeding, and thermonociception. Therefore, we suggest that N/OFQ may participate in these snail functions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Opioid peptides play a key role in ethanol reinforcement and may also represent important determinants in brain sensitivity to ethanol through modulation of nigrostriatal dopaminergic activity. Regulation of opioid levels by peptidase-degrading enzymes could be relevant in ethanol's actions. The aim of this work was to study the acute ethanol (2.5 g/kg) effects on the activity and mRNA expression of enkephalinase (NEP) and aminopeptidase N (APN) in the rat substantia nigra (SN) and the anterior-medial (amCP) and medial-posterior (mpCP) regions of the caudate-putamen (CP). Enzymatic activities were measured by fluorometric assays and mRNA expression by reverse transcriptase polymerase chain reaction. Acute ethanol administration differentially altered peptidase activities and mRNA expression with different kinetics. Ethanol increased and decreased NEP mRNA levels in the SN and amCP, respectively, but produced biphasic effects in the mpCP. APN mRNA levels were increased by ethanol in all brain regions. Ethanol induced a transient and long-lasting increase in NEP (mpCP) and APN (amCP) activities, respectively. Peptidase activities were not changed by ethanol in the SN. Our results indicate that striatal NEP and APN are important ethanol targets. Ethanol-induced changes in these neuropeptidases in the CP could contribute to the mechanisms involved in brain sensitivity to ethanol.

Anxiolytic effects of alcohol participate in the reinforcing properties of the drug, in which nucleus accumbens (NAcc) is implicated. The opioidergic system in NAcc is considered a main pathway involved in the emotional responses of animals: rats microinjected with morphine in NAcc and the systemic administration of μ-opioid receptors (MOR) agonists yield low anxiety scores in the elevated plus maze (EPM), a behavioral test of anxiety. However, the specific participation of NAcc MOR in the anxiolytic effect of ethanol has not been studied. AC5, a cAMP-synthezising adenylyl-cyclase, is highly expressed in NAcc; it is negatively coupled to MOR and has been implicated in anxiety levels of animals. We evaluated the anxiolytic effects of an intra-gastric administration of ethanol (2.5 g/kg) in animals subjected to EPM at 1, 4, and 8 h after drug or water exposure. Locomotion was assayed with the open-field test; we also measured accumbal AC5 and MOR mRNA levels by RT-PCR. After 1 h, ethanol-exposed animals showed anxiolytic-like behavior, as well as decreased and increased AC5 and MOR expression in NAcc, respectively. Intra-accumbal injection of β-funaltrexamine (FNA), a MOR antagonist, did not block ethanol-induced anxiolysis, rather it induced a tendency to increase anxiety levels in the water-exposed group. FNA partially decreased accumbal AC5 expression in ethanol-treated rats. We concluded that AC5 in NAcc is participating in the emotional effects of ethanol; that MOR was not mediating the drug-induced AC5 reduction in NAcc nor the ethanol-induced anxiolysis. MOR only might be involved in basal levels of anxiety of animals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Herpes simplex virus (HSV) infections are highly prevalent and may have devastating consequences if transmitted to newborns. The highest risk of transmission is when the mother has primary HSV infection (rather than recurrence of chronic infection) late in pregnancy. Clinicians should obtain a careful history, performing serologic testing and counseling as appropriate. Delayed diagnosis of neonatal HSV is associated with high mortality. Even with adequate treatment, permanent sequelae, such as cerebral palsy and developmental delay, may occur. Clinicians should develop prudent strategies to avoid primary HSV acquisition during pregnancy, and provide prophylaxis or treatment when indicated.

Opioid peptides play a key role in ethanol reinforcement and alcohol drinking behavior. However, regulation of opioid levels by peptidase-degrading activities in ethanol's actions in brain is still unclear. The aim of this work was to study the acute effects of ethanol (2.5 g/kg) on enkephalinase (NEP) and aminopeptidase N (APN) activities and expression in regions of the mesocorticolimbic system, as well as on corticosterone levels in serum for up to 24 h after administration. Enzymatic activities were measured by fluorometric assays, mRNA's expression by reverse transcriptase polymerase chain reaction (RT-PCR) and corticosterone levels by radioimmunoassay. Acute ethanol administration modified peptidase activity and expression with different kinetics. Ethanol induced a transitory increase and decrease in NEP and APN activities in the frontal cortex (FC) and ventral tegmental area (VTA), whereas only increases in these activities were observed in the nucleus accumbens (NAcc). Ethanol induced an increase in NEP mRNA in the FC and decreases in APN mRNA in the FC and NAcc. In contrast, ethanol produced biphasic effects on both enzymes expression in the VTA. Corticosterone levels were not changed by ethanol. Our results suggest that NEP and APN could play a main role in ethanol reinforcement through regulation of opioid levels in mesolimbic areas.

Background: The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals.A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot., Results: The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region., Conclusions: This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat., (© 2011 Ortega-Legaspi et al; licensee BioMed Central Ltd.)

Vertebrate oocytes actively contribute to follicle development by secreting a variety of growth factors, among which bone morphogenetic protein 15 (BMP15/Bmp15) and growth differentiation factor 9 (GDF9/Gdf9) have been paid particular attention. In the present study, we describe the cellular localization, the developmental profiles, and the response to unilateral ovariectomy (a procedure implying the surgical removal of one of the ovaries) of protein and mRNA steady-state levels of Bmp15 and Gdf9 in the ovary of European sea bass, an important fish species for marine aquaculture industry. In situ hybridization and immunohistochemistry demonstrated that the oocyte is the main production site of Bmp15 and Gdf9 in European sea bass ovary. During oocyte development, Bmp15 protein expression started to be detected only from the lipid vesicle stage onwards but not in primary pre-vitellogenic (i.e. perinucleolar) oocytes as the bmp15 mRNA already did. Gdf9 protein and gdf9 mRNA expression were both detected in primary perinucleolar oocytes and followed similar decreasing patterns thereafter. Unilateral ovariectomy induced a full compensatory growth of the remaining ovary in the 2-month period following surgery (Á. García-López, M.I. Sánchez-Amaya, C.R. Tyler, F. Prat 2011). The compensatory growth elicited different changes in the expression levels of mRNA and protein of both factors, although the involvement of Bmp15 and Gdf9 in the regulatory network orchestrating such process remains unclear at present. Altogether, our results establish a solid base for further studies focused on elucidating the specific functions of Bmp15 and Gdf9 during primary and secondary oocyte growth in European sea bass., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A real-time PCR-based gene expression survey was performed on isolated European sea bass follicles from primary growth to late vitellogenesis. Expression levels of 18 transcripts with demonstrated relevance during oogenesis, encoding gonadotropin, thyrotropin, estrogen, androgen, and vitellogenin receptors, steroidogenesis-related as well as growth and transcription factors were measured. Primary oocytes showed high mRNA levels of insulin-like growth factors 1 and 2, bone morphogenetic protein 4, estrogen receptor 2b, androgen receptor b, and SRY-box containing gene 17 together with low transcript amounts of gonadotropin receptors. Follicles at the lipid vesicles stage (i.e., the beginning of the secondary growth phase) showed elevated mRNA amounts of follicle stimulating hormone receptor (fshr) and anti-Mullerian hormone. Early-to-mid vitellogenic follicles showed high mRNA levels of fshr and cytochrome P450, family 19, subfamily A, polypeptide 1a while mid-to-late vitellogenic follicles expressed increasing transcript amounts of luteinizing hormone/choriogonadotropin receptor, steroidogenic acute regulatory protein, and estrogen receptors 1 and 2a. The molecular data presented here may serve as a solid base for future studies focused on unraveling the specific mechanisms orchestrating follicular development in teleost fish., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unilateral ovariectomy (ULO) was performed in European sea bass (Dicentrarchus labrax L.) during late pre-vitellogenesis/early vitellogenesis. Plasma steroid levels and the expression of a suite of potential oogenesis-relevant genes in the ovary, brain, and pituitary were evaluated with the aim of understanding their involvement in the compensatory oocyte development occurring within the remaining ovarian lobe. After 69 days of surgery the remaining ovarian lobe in ULO fish was gravimetrically equivalent to an intact-paired ovary of sham operated, control fish. This compensatory ovarian growth was based on an increased number of early perinucleolar oocytes and mid-late stage vitellogenic follicles without an apparent recruitment of primary oocytes into the secondary growth phase. Plasma steroid levels were similar in ULO and control females at all time points analyzed, suggesting an increased steroid production of the remaining ovarian lobe in hemi-castrated females. Results of the gene expression survey conducted indicate that the signaling pathways mediated by Fsh and Gnrh1 constitute the central axes orchestrating the observed ovarian compensatory growth. In addition, steroid receptors, Star protein, Igfs, and members of the transforming growth factor beta superfamily including anti-Mullerian hormone and bone morphogenetic protein 4 were identified as potentially relevant players within this process, although their specific actions and interactions remain to be established. Our results demonstrate that ULO provides an excellent in vivo model for elucidating the interconnected endocrine and molecular mechanisms controlling oocyte development in European sea bass.

Background: The insular cortex (IC) receives somatosensory afferent input and has been related to nociceptive input. It has dopaminergic terminals and D1 (D1R) -excitatory- and D2 (D2R) -inhibitory- receptors. D2R activation with a selective agonist, as well as D1R blockade with antagonists in the IC, diminish neuropathic nociception in a nerve transection model. An intraplantar injection of carrageenan and acute thermonociception (plantar test) were performed to measure the response to inflammation (paw withdrawal latency, PWL). Simultaneously, a freely moving microdyalisis technique and HPLC were used to measure the release of dopamine and its metabolites in the IC. Plantar test was applied prior, one and three hours after inflammation. Also, mRNA levels of D1 and D2R's were measured in the IC after three hours of inflammation., Results: The results showed a gradual decrease in the release of dopamine, Dopac and HVA after inflammation. The decrease correlates with a decrease in PWL. D2R's increased their mRNA expression compared to the controls. In regard of D1R's, there was a decrease in their mRNA levels compared to the controls., Conclusions: Our results showed that the decreased extracellular levels of dopamine induced by inflammation correlated with the level of pain-related behaviour. These results also showed the increase in dopaminergic mediated inhibition by an increase in D2R's and a decrease in D1R's mRNA. There is a possible differential mechanism regarding the regulation of excitatory and inhibitory dopaminergic receptors triggered by inflammation.

The anterior cingulate cortex (ACC) and muscarinic receptors modulate pain. This study investigates changes in the expression of muscarinic-1 and -2 receptors (M1R, M2R) in rats' ACC (cg1-rostral- and cg2-caudal) using a model of neuropathic pain by denervation, measured as autotomy score (AS) for 8 days. Changes were analysed with painful stimuli and with scopolamine into the ACC prior to this scheme. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence to determine M1R and M2R's mRNA and protein levels, respectively. Animals were divided in low, medium and high AS groups. Cg1 showed decreased mRNA levels for both M1R and M2R in the low AS group, as opposed to an increased expression in the medium and high AS groups. Both receptors correlated positively with AS in these groups. In the scopolamine-treated animals there was an increase in mRNA levels for both receptors in cg1, whereas in cg2, mRNA levels of M1R decreased in all the AS and scopolamine groups. The increased M2R mRNA in cg2 correlated with AS in the low, medium and high AS groups whereas all the scopolamine groups showed an increase. Immunoreactivity of the M2R in cg1 decreased in the medium AS group in comparison to controls but scopolamine treatment produced an increase in the medium scopolamine AS group compared to the medium AS group. The M1R in cg1 and both receptors in cg2 showed no immunoreactivity changes. These results highlight the role of the M2R in cg1 related to the degree of autotomy., (Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Food-restricted animals present metabolic adaptations that facilitate food-seeking behavior and decelerate energy utilization by reducing the hypothalamus-pituitary-thyroid (HPT) axis function. Stress by dehydration induces an anorexic behavior in rats, loss of weight and reduced food intake when compared to ad libitum fed animals, however these alterations are accompanied by HPT axis changes such as increased serum thyrotropin levels and enhanced expression of thyrotropin-releasing hormone (TRH) in the paraventricular nucleus of the hypothalamus, which is considered as anorexigenic peptide. In contrast, a pair-fed group conformed by forced-food-restricted animals (FFR) (eating the exact same amount of food as dehydration-induced anorexic rats--DIA rats) present decreased TRH mRNA levels. NPY synthesis in the arcuate nucleus and orexin-expressing neurons from the lateral hypothalamic area (LHA) are activated during food restriction. These brain structures project into PVN, suggesting that NPY and orexins are possible factors involved in TRHergic neuron activation in DIA rats. Leptin signaling is another likely factor to be involved in TRH differential expression. Therefore, to gain more insight into the regulation of the feeding behavior in the experimental models, we analyzed Y1, Y5, Ox1-R and Ob-R(b) mRNA levels in PVN and prepro-orexin in LHA, since their signaling to the PVN might be altering TRH synthesis and feeding in DIA animals. Prepro-orexinergic cells were activated in FFR animals; Ox1-R and Y1 expression was reduced in FFR vs. controls or DIA group. Compensatory changes in PVN receptor expression of some feeding-related peptides in anorexic rats may alter TRHergic neural response to energy demands.

Wistar rats subjected to dehydration-induced anorexia (DIA), with 2.5% NaCl solution as drinking water for 7 days, decrease by 80% their food intake and present some changes common to pair-fed food restricted rats (FFR) such as: weight loss, decreased serum leptin and expression of orexigenic arcuate peptides, increasing the anorexigenic ones and serum corticosterone levels. In contrast, the response of the HPT axis differs: DIA animals have increased TRH expression in PVN and present primary as opposed to the tertiary hypothyroidism of the FFR. Exclusive to DIA is the activation of CRHergic neurons in the lateral hypothalamus (LH) that project to PVN. Since TRH neurons of the PVN contain CRH receptors, we hypothesized that the differences in the response of the HPT axis to DIA could be due to CRH regulating TRHergic neurons. CRH effect was first evaluated on TRH expression of cultured hypothalamic cells where TRH mRNA levels increased after 1h with 0.1nM of CRH. We then measured the mRNA levels of CRH receptors in the PVN of male and female rats subjected to DIA; only those of CRH-R2 were modulated (down-regulated). The CRH-R2 antagonist antisauvagine-30 was therefore injected into the PVN of male rats, during the 7 days of DIA. Antisauvagine-30 induced a higher food intake than controls, and impeded the changes produced by DIA on the HPT axis: PVN TRH mRNA, and serum TH and TSH levels were decreased to similar values of FFR animals. Results corroborate the anorexigenic effect of CRH and show its role, acting through CRH-R2 receptors, in the activation of TRHergic PVN neurons caused by DIA. These new data further supports clinical trials with CRH-R2 antagonists in anorexia nervosa patients.