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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

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.

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.)