Microglia react to partner loss in a sex- and brain site-specific manner in prairie voles.

Positive social relationships are paramount for the survival of mammals and beneficial for mental and physical health, buffer against stressors, and even promote appropriate immune system functioning. By contrast, impaired social relationships, social isolation, or the loss of a bonded partner lead to aggravated physical and mental health. For example, in humans partner loss is detrimental for the functioning of the immune system and heightens the susceptibility for the development of post-traumatic stress disorders, anxiety disorders, and major depressive disorders. To understand potential underlying mechanisms, the monogamous prairie vole can provide important insights. In the present study, we separated pair bonded male and female prairie voles after five days of co-housing, subjected them to the forced swim test on the fourth day following separation, and studied their microglia morphology and activation in specific brain regions. Partner loss increased passive stress-coping in male, but not female, prairie voles. Moreover, partner loss was associated with microglial priming within the parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) in male prairie voles, whereas in female prairie voles the morphological activation within the whole PVN and the prelimbic cortex (PrL) was decreased, marked by a shift towards ramified microglial morphology. Expression of the immediate early protein c-Fos following partner loss was changed within the PrL of male, but not female, prairie voles. However, the loss of a partner did not affect the investigated aspects of the peripheral immune response. These data suggest a potential sex-dependent mechanism for the regulation of microglial activity following the loss of a partner, which might contribute to the observed differences in passive stress-coping. This study furthers our understanding of the effects of partner loss and its short-term impact on the CNS as well as the CNS immune system and the peripheral innate immune system in both male and female prairie voles.

Impact of manual therapy on body posture-3-D analysis with rasterstereography - pilotstudy.

INTRODUCTION: The relationship between posture and temporomandibular disease (TMD) is unclear. The aim of our study was to determine the influence of manual therapy (MT) on posture in TMD patients compared with healthy subjects. MATERIAL/METHOD: After consideration of inclusion and exclusion criteria, 30 subjects were included. These were divided into two groups: group A comprised 15 healthy subjects and group B 15 patients with present proven TMD disease. Rasterstereographic images were taken at different times. Group A subjects were scanned twice within half a year and group B before initiation as well as after the first MT and after completion of the prescribed MT. The different posture variables were calculated using DIERS Formetric software. RESULTS: To illustrate the differences between the two groups, 10 different postural variables were examined. Significant differences between the two groups were observed in pelvic tilt, surface rotation, and kyphotic apex. Pelvic tilt: mean = 7.581, p-value = 0.029; surface rotation: mean = 3.098, p = 0.049; and mean kyphotic apex = 11.538 and 11.946, respectively, with p-values of 0.037 and 0.029, respectively. CONCLUSION: MT leads to a change in posture in TMD patients. This could influence the course of TMD treatment.

Touch sensation requires the mechanically gated ion channel ELKIN1.

Touch perception is enabled by mechanically activated ion channels, the opening of which excites cutaneous sensory endings to initiate sensation. In this study, we identify ELKIN1 as an ion channel likely gated by mechanical force, necessary for normal touch sensitivity in mice. Touch insensitivity in Elkin1-/- mice was caused by a loss of mechanically activated currents (MA currents) in around half of all sensory neurons activated by light touch (low-threshold mechanoreceptors). Reintroduction of Elkin1 into sensory neurons from Elkin1-/- mice restored MA currents. Additionally, small interfering RNA-mediated knockdown of ELKIN1 from induced human sensory neurons substantially reduced indentation-induced MA currents, supporting a conserved role for ELKIN1 in human touch. Our data identify ELKIN1 as a core component of touch transduction in mice and potentially in humans.

Neuroligins in neurodevelopmental conditions: how mouse models of de novo mutations can help us link synaptic function to social behavior.

Neurodevelopmental conditions (or neurodevelopmental disorders, NDDs) are highly heterogeneous with overlapping characteristics and shared genetic etiology. The large symptom variability and etiological heterogeneity have made it challenging to understand the biological mechanisms underpinning NDDs. To accommodate this individual variability, one approach is to move away from diagnostic criteria and focus on distinct dimensions with relevance to multiple NDDs. This domain approach is well suited to preclinical research, where genetically modified animal models can be used to link genetic variability to neurobiological mechanisms and behavioral traits. Genetic factors associated with NDDs can be grouped functionally into common biological pathways, with one prominent functional group being genes associated with the synapse. These include the neuroligins (Nlgns), a family of postsynaptic transmembrane proteins that are key modulators of synaptic function. Here, we review how research using Nlgn mouse models has provided insight into how synaptic proteins contribute to behavioral traits associated with NDDs. We focus on how mutations in different Nlgns affect social behaviors, as differences in social interaction and communication are a common feature of most NDDs. Importantly, mice carrying distinct mutations in Nlgns share some neurobiological and behavioral phenotypes with other synaptic gene mutations. Comparing the functional implications of mutations in multiple synaptic proteins is a first step towards identifying convergent neurobiological pathways in multiple brain regions and circuits.

Optical Carbon Dioxide Detection in the Visible Down to the Single Digit ppm Range Using Plasmonic Perfect Absorbers.

To tackle climate change and reduce CO2 emissions, it is important to measure CO2 output precisely. Even though there are many different techniques, no simple and cheap optical method in the visible is available. This work studies plasmonically enhanced optical carbon dioxide sensors in the visible wavelength range. The sensor samples are based on an inert plasmonic perfect absorber, which can be easily and cheaply fabricated by colloidal etching lithography. A CO2-sensitive polyethylenimine (PEI) layer is then spin-coated on top to complete the samples. The samples are examined continuously by microspectroscopy during different CO2 exposures to track spectral changes, particularly the position of the resonance centroid wavelength. The samples exhibit a resonance shift of up to 7 nm, depending on the CO2 concentration and the temperature. The temperature influences the rise time as well as the sensitive concentration range. The concentration dependence of the resonance shift overall follows the shape of a Langmuir isotherm, which includes a nearly linear relation at lower concentrations and elevated temperatures and a saturating behavior at higher concentrations and lower temperatures. The results indicate that a sensitivity in the full range from 100 vol % to below 1 ppm can be achieved. The samples degenerate in a dry inert atmosphere in a matter of days but are useable over multiple weeks when exposed to humidity and CO2. The PEI reacts very selectively to CO2, showing no response to CO, NH3, NO2, CH4, H2, and only a very small response to O2. Overall, polyethylenimine is very promising as a CO2-sensitive material for many practical sensing applications over a wide range of concentrations. An adjustment of the temperature is mandatory to control the sensitivity and response time.

Lost connections: Oxytocin and the neural, physiological, and behavioral consequences of disrupted relationships.

In humans and rodent animal models, the brain oxytocin system is paramount for facilitating social bonds, from the formation and consequences of early-life parent-infant bonds to adult pair bond relationships. In social species, oxytocin also mediates the positive effects of healthy social bonds on the partners' well-being. However, new evidence suggests that the negative consequences of early neglect or partner loss may be mediated by disruptions in the oxytocin system as well. With a focus on oxytocin and its receptor, we review studies from humans and animal models, i.e. mainly from the biparental, socially monogamous prairie vole (Microtus ochrogaster), on the beneficial effects of positive social relationships both between offspring and parents and in adult partners. The abundance of social bonds and benevolent social relationships, in general, are associated with protective effects against psycho- and physiopathology not only in the developing infant, but also during adulthood. Furthermore, we discuss the negative effects on well-being, emotionality and behavior, when these bonds are diminished in quality or are disrupted, for example through parental neglect of the young or the loss of the partner in adulthood. Strikingly, in prairie voles, oxytocinergic signaling plays an important developmental role in the ability to form bonds later in life in the face of early-life neglect, while disruption of oxytocin signaling following partner loss results in the emergence of depressive-like behavior and physiology. This review demonstrates the translational value of animal models for investigating the oxytocinergic mechanisms that underlie the detrimental effects of developmental parental neglect and pair bond disruption, encouraging future translationally relevant studies on this topic that is so central to our daily lives.

Abandoned prairie vole mothers show normal maternal care but altered emotionality: Potential influence of the brain corticotropin-releasing factor system.

When fathers leave the family, mothers are at increased risk of developing depression and anxiety disorders. In biparental, socially monogamous prairie voles (Microtus ochrogaster), sudden bond disruption increases passive stress-coping, indicative of depressive-like behavior, and acts as chronic stressor in both males and females. However, the consequences of separation in lactating prairie vole mothers are unknown. In the present study, following 18 days of cohousing, half of the prairie vole pairs were separated by removing the male. In early lactation, maternal care was unaffected by separation, whereas anxiety-related behavior and passive stress-coping were significantly elevated in separated mothers. Separation significantly increased corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus under basal conditions, similar to levels of paired females after acute exposure to forced swim stress. A second cohort of lactating prairie voles was infused intracerebroventricularly with either vehicle or the CRF receptor antagonist D-Phe just prior to behavioral testing. The brief restraining during acute infusion significantly decreased arched back nursing in vehicle-treated paired and separated groups, whereas in the D-Phe-treated separated group the behavior was not impaired. Furthermore, in the latter, anxiety-related behavior and passive stress-coping were normalized to levels similar to vehicle-treated paired mothers. In conclusion, maternal investment is robust enough to withstand loss of the partner, whereas the mother's emotionality is affected, which may be - at least partly - mediated by a CRF-dependent mechanism. This animal model has potential for mechanistic studies of behavioral and physiological consequences of partner loss in single mothers.

Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity.

Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body's main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS.