Abstract
Postnatal development includes dramatic changes in gonadal hormones and the many social behaviors they help regulate, both in rodents and humans. Parental care-seeking is the most salient ...social interaction in neonates and infants, play and prosocial behaviors are commonly studied in juveniles, and the development of aggression and sexual behavior begins in peripubertal stages but continues through late adolescence into adulthood. Although parental behaviors are shown after reproductive success in adulthood, alloparenting behaviors are actually high in juveniles as well. These behaviors are sensitive to both early-life organizational effects of gonadal hormones and later-life activational regulation. However, changes in circulating gonadal hormones and the display of the previous behaviors over development differ between rats, mice, and humans. These endpoints are of interest to endocrinologist, toxicologists, and neuroscientists because of their relevance to mental health disorders and their vulnerability to effects of endocrine-disrupting chemical exposure. As such, the goal of this mini-review is to succinctly describe and relate the postnatal development of gonadal hormones and social behaviors to each other, over time, and across animal models. Ideally, this will help identify appropriate animal models and age ranges for continued study of both normative development and in contexts of environmental disruption.
This mini-review describes postnatal changes in gonadal hormones and the display of hormone-sensitive social behaviors in rats, mice, and humans to help identify best time points for continued study.
Highlights • Polychlorinated biphenyls affect a range of social and reproductive behaviors. • Effects may be mediated via hormonal, dopaminergic, and/or glutamateric mechanisms. • Most effects depend ...on specific congeners, dose, exposure time, and sex of animal. • Additional research using human-relevant exposure levels and mixtures is needed.
Endurance exercise has been shown to be a positive regulator of skeletal muscle metabolic function. Changes in mitochondrial dynamics (fusion and fission) have been shown to influence mitochondrial ...oxidative capacity. We therefore tested whether genetic disruption of mitofusins (Mfns) affected exercise performance in adult skeletal muscle. We generated adult-inducible skeletal muscle-specific Mfn1 (iMS-Mfn1KO), Mfn2 (iMS-Mfn2KO), and Mfn1/2 (iMS-MfnDKO) knockout mice. We assessed exercise capacity by performing a treadmill time to exhaustion stress test before deletion and up to 8 wk after deletion. Analysis of either the iMS-Mfn1KO or the iMS-Mfn2KO did not reveal an effect on exercise capacity. However, analysis of iMS-MfnDKO animals revealed a progressive reduction in exercise performance. We measured individual electron transport chain (ETC) complex activity and observed a reduction in ETC activity in both the subsarcolemmal and intermyofibrillar mitochondrial fractions specifically for NADH dehydrogenase (complex I) and cytochrome- c oxidase (complex IV), which was associated with a decrease in ETC subunit expression for these complexes. We also tested whether voluntary exercise training would prevent the decrease in exercise capacity observed in iMS-MfnDKO animals ( n = 10/group). However, after 8 wk of training we did not observe any improvement in exercise capacity or ETC subunit parameters in iMS-MfnDKO animals. These data suggest that the decrease in exercise capacity observed in the iMS-MfnDKO animals is in part the result of impaired ETC subunit expression and ETC complex activity. Taken together, these results provide strong evidence that mitochondrial fusion in adult skeletal muscle is important for exercise performance. NEW & NOTEWORTHY This study is the first to utilize an adult-inducible skeletal muscle-specific knockout model for Mitofusin (Mfn)1 and Mfn2 to assess exercise capacity. Our findings reveal a progressive decrease in exercise performance with Mfn1 and Mfn2 deletion. The decrease in exercise capacity was accompanied by impaired oxidative phosphorylation specifically for complex I and complex IV. Furthermore, voluntary exercise training was unable to rescue the impairment, suggesting that normal fusion is essential for exercise-induced mitochondrial adaptations.
Ever growing populations in cities are associated with a major increase in road vehicles and air pollution. The overall high levels of urban air pollution have been shown to be of a significant risk ...to city dwellers. However, the impacts of very high but temporally and spatially restricted pollution, and thus exposure, are still poorly understood. Conventional approaches to air quality monitoring are based on networks of static and sparse measurement stations. However, these are prohibitively expensive to capture tempo-spatial heterogeneity and identify pollution hotspots, which is required for the development of robust real-time strategies for exposure control. Current progress in developing low-cost micro-scale sensing technology is radically changing the conventional approach to allow real-time information in a capillary form. But the question remains whether there is value in the less accurate data they generate. This article illustrates the drivers behind current rises in the use of low-cost sensors for air pollution management in cities, while addressing the major challenges for their effective implementation.
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•Impacts on the health of city dwellers due to high air pollution exposure are unknown.•Conventional sparse monitoring stations are unable to identify pollution hotspots.•Low-cost micro-scale sensing allows capturing real-time high-grained pollution data.•Fundamental drivers behind the rise of low-cost sensing and challenges are discussed.
Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking ...(e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage.
Polychlorinated biphenyls (PCBs) are ubiquitous in the environment and exposure to them is associated with immune, endocrine and neural dysfunction. Effects of PCBs on inflammation and immunity are ...best described in spleen and blood, with fewer studies on neural tissues. This is an important gap in knowledge, as molecules typically associated with neuroinflammation also serve neuromodulatory roles and interact with hormones in normal brain development. The current study used Sprague-Dawley rats to assess whether gestational PCB exposure altered hypothalamic gene expression and serum cytokine concentration in neonatal animals given an immune challenge. Dams were fed wafers containing a mixture of PCBs at an environmentally relevant dose and composition (20 μg/kg, 1:1:1 Aroclor 1242:1248:1254) or oil vehicle control throughout their pregnancy. One day old male and female offspring were treated with an inflammatory challenge (lipopolysaccharide, LPS, 50 μg/kg, sc) or saline vehicle control approximately 3.5 h prior to tissue collection. Across both basal and activated inflammatory states, PCB exposure caused greater expression of a subset of inflammatory genes in the hypothalamus and lower expression of genes involved in dopamine, serotonin, and opioid systems compared to oil controls. PCB exposure also altered reactions to inflammatory challenge: it reversed the normal decrease in Esr2 hypothalamic expression and induced an abnormal increase in IL-1b and IL-6 serum concentration in response to LPS. Many of these effects were sex specific. Given the potential long-term consequences of neuroimmune disruption, our findings demonstrate the need for further research.
•Perinatal polychlorinated biphenyls (PCBs) alter neonatal hypothalamic gene expression•PCBs reduce expression of dopamine-related targets in males and females•PCBs alter serum cytokine responses to inflammatory LPS differently between sexes•PCBs increase expression of selected neuroimmune signals independent of LPS effect
Endocrine disrupting chemicals (EDCs) are widespread environmental contaminants that affect many neuroendocrine functions. The brain is particularly vulnerable to EDCs during critical periods of ...gestational development when gonadal hormones exert organizational effects on sexually dimorphic behaviors later in life. Peripubertal development is also a time of continued neural sensitivity to organizing effects of hormones, yet little is known about EDC actions at these times. We sought to determine effects of prenatal or juvenile exposures to a class of EDCs, polychlorinated biphenyls (PCBs) at human-relevant dosages on development, physiology, and social and anxiety-related behaviors later in life, and the consequences of a second juvenile “hit” following prenatal treatment. We exposed male and female Sprague–Dawley rats to PCBs (Aroclor 1221, 1mg/kg/day, ip injection) and/or vehicle during prenatal development (embryonic days 16, 18, 20), juvenile development (postnatal days 24, 26, 28), or both. These exposures had differential effects on behaviors in sex and age-dependent ways; while prenatal exposure had more effects than juvenile, juvenile exposure often modified or unmasked the effects of the first hit. Additionally, females exhibited altered social and anxiety behavior in adolescence, while males displayed small but significant changes in sociosexual preferences in adulthood. Thus, the brain continues to be sensitive to organizing effects of EDCs through juvenile development. As humans are exposed to EDCs throughout multiple periods in their life, these findings have implications for our understanding of EDC effects on physiology and behavior.
•Prenatal PCB exposure alters social and anxiety behaviors, especially in females.•Juvenile PCB exposure affects male sociosexual preference behaviors.•Prenatal and juvenile PCB exposures have both individual and interacting effects.•Adolescence may be a second critical period for PCB exposure effects.
Although concussions are a popular focus of neurotrauma research, subconcussions occur with higher frequency but are less well-studied. A subconcussion is an impact to the head that does not result ...in immediately diagnosable concussion but can result in later neurological consequences. Repeat subconcussions can produce behavioral impairments and neuropathology that is similar to or worse than those seen following a single concussion. The current study modified a previously established closed head injury model of concussion to create a subconcussion model and examines sex differences in behavioral responses to repeated subconcussion in the adult rat. Rats received a single concussion, single or repeat subconcussions, or no impact and behavior was monitored from 2 h through 31 days post-injury. A single concussion or repeat subconcussion resulted in deficits in locomotion, righting reflexes, and recognition memory. The degree of deficit induced by repeat subconcussions were either similar (righting reflexes) or greater/more persistent (locomotor deficits and recognition memory) than that of a concussion. Single subconcussion resulted in acute deficits that were mild and limited to righting reflexes and locomotion. Sex differences were observed in responses to repeat subconcussion: females showed greater deficits in righting reflexes, locomotion, and vestibular function, while males showed greater alterations in anxiety and depressive-like behavior. This study established a model of subconcussive impact where a single subconcussive impact resulted in minimal behavioral deficits but repeat subconcussions resulted in deficits similar to or worse than a single concussion. Our data also suggest sex differences in behavioral responses to both concussive and subconcussive impacts.
•This study created a model of closed head repeat subconcussion in the adult rat using a controlled cortical impact device.•Repeat subconcussion produced more locomotor and memory deficits but similar righting reflex deficits as single concussion.•Female rats showed larger deficits than males in righting reflexes, locomotion, and vestibular function.•Male rats showed larger alterations in anxiety-like behavior compared to females.
Polychlorinated biphenyls are ubiquitous environmental contaminants linked with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; ...however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previous work in neonatal or adolescent rats by investigating longer-term effects of perinatal PCB exposure on later neuroimmune responses to an inflammatory challenge in adulthood. Male and female Sprague-Dawley rats were exposed to a low-dose, environmentally relevant, mixture of PCBs (Aroclors 1242, 1248, and 1254, 1:1:1, 20μg / kg dam BW per gestational day) or oil control during gestation and via lactation. Upon reaching adulthood, rats were given a mild inflammatory challenge with lipopolysaccharide (LPS, 50μg / kg BW, ip) or saline control and then euthanized 3hours later for gene expression analysis or 24hours later for immunohistochemical labeling of Iba1+ microglia. PCB exposure did not alter gene expression or microglial morphology independently, but instead interacted with the LPS challenge in brain region- and sex–specific ways. In the female hypothalamus, PCB exposure blunted LPS responses of neuroimmune and neuromodulatory genes without changing microglial morphology. In the female prefrontal cortex, PCBs shifted Iba1+ cells from reactive to hyperramified morphology in response to LPS. Conversely, in the male hypothalamus, PCBs shifted cell phenotypes from hyperramified to reactive morphologies in response to LPS. The results highlight the potential for long-lasting effects of environmental contaminants that are differentially revealed over a lifetime, sometimes only after a secondary challenge. These neuroimmune endpoints are possible mechanisms for PCB effects on a range of neural dysfunction in adulthood, including mental health and neurodegenerative disorders. The findings suggest possible interactions with other environmental challenges that also influence neuroimmune systems.
•Early PCB exposure alters neuroimmune responses to adult inflammatory challenge•PCBs alter Tlr4 and Nfkb gene expression responses to LPS independent of cytokines•PCBs alter hypothalamic dopamine, CRH, aromatase gene expression responses to LPS•PCBs shift microglial morphological responses to LPS in hypothalamus and PFC•PCB effects differed between sexes, brain regions, and from those at earlier ages
Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their ...effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments.
•Prenatal and juvenile PCB exposures affect gene expression in adult rat brains.•The effect of a single exposure is often reversed by a second hit.•Males are more sensitive to long-term effects of PCBs than females.•Gene expression in the medial preoptic area was the most affected by PCBs.
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