RESUMO

BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.

In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.

Assuntos

RESUMO

We explored a possible role of oxytocin (OXT) for the onset and maintenance of rabbit maternal behavior by: (a) confirming that a selective oxytocin receptor antagonist (OTA) widely used in rodents selectively binds to OXT receptors (OXTR) in the rabbit brain and (b) determining the effect of daily intracerebroventricular (icv) injections of OTA to primiparous and multiparous does from gestation day 29 to lactation day 3. OTA efficiently displaced the high affinity, selective oxytocin receptor (OXTR) radioligand, 125 I-labeled ornithine vasotocin analog (125 I-OVTA), but was much less effective at displacing the selective V1a vasopressin receptor radioligand, 125 I-labeled linear vasopressin, thus showing high affinity and selectivity of OTA for rabbit OXTR as in rodents. Further, ICV OTA injections did not modify nest-building, latency to enter the nest box, time spent nursing or the amount of milk produced, relative to vehicle-injected does. The percentage of mothers suckling the litter was also similar between both groups, regardless of parity. Together, our results do not support a role of OXT for the initiation or maintenance of rabbit maternal behavior. Future studies are warranted to determine if OXT participates in fine-tuning additional aspects of the maternal ethogram, for example, circadian periodicity of nursing and nest defense.

Assuntos

RESUMO

Prairie voles are a socially monogamous species that, after cohabitation with mating, form enduring pair bonds. The plastic mechanisms involved in this social behavior are not well-understood. Neurogenesis in adult rodents is a plastic neural process induced in specific brain areas like the olfactory bulbs (OB) and dentate gyrus (DG) of the hippocampus. However, it is unknown how cell survival is modulated by social or sexual experience in prairie voles. This study aimed to evaluate if cohabitation with mating and/or social exposure to a vole of the opposite sex increased the survival of the new cells in the main and accessory OB and DG. To identify the new cells and evaluate their survival, voles were injected with the DNA synthesis marker 5-bromo-2'-deoxyuridine (BrdU) and were randomly distributed into one of the following groups: (A) Control (C), voles that did not receive any sexual stimulation and were placed alone during the behavioral test. (B) Social exposure (SE), voles were individually placed in a cage equally divided into two compartments by an acrylic screen with small holes. One male and one female were placed in opposite compartments. (C) Social cohabitation with mating (SCM), animals mated freely. Our findings demonstrated that SCM females had increases in the number of new cells (BrdU-positive cells) in the main olfactory bulb and new mature neurons (BrdU/NeuN-positive cells) in the glomerular layer (GlL). In contrast, these new cells decrease in males in the SE and SCM conditions. In the granular cell layer (GrL), SCM females had more new cells and neurons than the SE group. In the accessory olfactory bulb, in the anterior GlL, SCM decreased the number of new cells and neurons in females. On the other hand, in the DG, SCM and SE increase the number of new cells in the suprapyramidal blade in female voles. Males from SCM express more new cells and neurons in the infrapyramidal blade compared with SE group. Comparison between male and females showed that new cells/neurons survival was sex dependent. These results suggest that social interaction and sexual behavior modulate cell survival and influence the neuronal fate in a sex-dependent manner, in the OB and DG. This study will contribute to understand neural mechanisms of complex social and pair bond behaviors in the prairie voles; supporting adult neurogenesis as a plastic mechanism potentially involved in social monogamous strategy.

RESUMO

Around 5 % of mammals are socially monogamous and both parents provide care to the pups (biparental, BP). Prairie voles are socially monogamous rodents extensively used to understand the neurobiological basis of pair bond formation and the consequences that the absence of one parent has in the offspring. Pair bonding, characterized by selective affiliation with a sexual partner, is facilitated in prairie voles by mating for 6 h or cohabitation without mating for 24 h. It was previously shown that prairie voles raised by their mother alone (monoparental, MP) show delayed pair bond formation upon reaching adulthood. In this study we evaluated the effects of BP and MP care provided on the offspring's development, ability to detect olfactory cues, preference for sexually relevant odors, display of sexual behavior, as well as the rewarding effects of mating. We also measured dopamine and serotonin concentration in the nucleus accumbens (ventral striatum) and dorsal striatum after cohabitation and mating (CM) to determine if differences in these neurotransmitters could underlie the delay in pair bond formation in MP voles. Our data showed that MP voles received less licking/grooming than BP voles, but no developmental differences between groups were found. No differences were found in the detection and discrimination of olfactory cues or preference for sexually relevant odors, as all groups innately preferred opposite sex odors. No differences were found in the display of sexual behavior. However, CM induced reinforcing properties only in BP males, followed by a preference for their sexual partner in BP but not MP males. BP males showed an increase in dopamine turnover (DOPAC/DA and HVA/DA) in the nucleus accumbens in comparison to MP voles. No differences in dopamine, serotonin or their metabolites were found in the dorsal striatum. Our results indicate that MP voles that received less licking behavior exhibit a delay in pair bond formation possibly because the sexual interaction is not rewarding enough.

Assuntos

RESUMO

Previous studies have related pair-bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially relevant regions have yet to be described. In this study, we used resting-state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair-bonding. Thirty-two male and female prairie voles were scanned at baseline, 24 hr, and 2 weeks after the onset of cohabitation. By using network-based statistics, we identified that the functional connectivity of a corticostriatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

Assuntos

RESUMO

BACKGROUND: Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. OBJECTIVE: To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. METHODS: We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). RESULTS: Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). CONCLUSIONS: Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.

RESUMO

Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.

Assuntos

RESUMO

Hashimoto's thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto's thyroiditis.

Assuntos

RESUMO

La tiroiditis de Hashimoto constituye la causa más frecuente de hipotiroidismo en las regiones sin deficiencia de yodo, es más frecuente en mujeres y muchas veces tiene asociación familiar. Los síntomas y signos del hipotiroidismo son sistémicos y dependen de la duración e intensidad de la deficiencia de la hormona tiroidea. Las manifestaciones neuromusculares, son excepcionalmente los únicos signos clínicos. Se presenta el caso de un paciente joven con una miopatía severa con rabdomiolisis como la única manifestación de hipotiroidismo severo debido a tiroiditis de Hashimoto.

Hashimoto’s thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto’s thyroiditis.

Assuntos