Density In Nucleus Research Articles

Intestinal gluconeogenesis controls the neonatal development of hypothalamic feeding circuits

ObjectiveIntestinal gluconeogenesis (IGN) regulates adult energy homeostasis in part by controlling the same hypothalamic targets as leptin. In neonates, leptin exhibits a neonatal surge controlling axonal outgrowth between the different hypothalamic nuclei involved in feeding circuits and autonomic innervation of peripheral tissues involved in energy and glucose homeostasis. Interestingly, IGN is induced during this specific time-window. We hypothesized that the neonatal pic of IGN also regulates the development of hypothalamic feeding circuits and sympathetic innervation of adipose tissues. MethodsWe genetically induced neonatal IGN by overexpressing G6pc1 the catalytic subunit of glucose-6-phosphatase (the mandatory enzyme of IGN) at birth or at twelve days after birth. The neonatal development of hypothalamic feeding circuits was studied by measuring Agouti-related protein (AgRP) and Pro-opiomelanocortin (POMC) fiber density in hypothalamic nuclei of 20-day-old pups. The effect of the neonatal induction of intestinal G6pc1 on sympathetic innervation of the adipose tissues was studied via tyrosine hydroxylase (TH) quantification. The metabolic consequences of the neonatal induction of intestinal G6pc1 were studied in adult mice challenged with a high-fat/high-sucrose (HFHS) diet for 2 months. ResultsInduction of intestinal G6pc1 at birth caused a neonatal reorganization of AgRP and POMC fiber density in the paraventricular nucleus of the hypothalamus, increased brown adipose tissue tyrosine hydroxylase levels, and protected against high-fat feeding-induced metabolic disorders. In contrast, inducing intestinal G6pc1 12 days after birth did not impact AgRP/POMC fiber densities, adipose tissue innervation or adult metabolism. ConclusionThese findings reveal that IGN at birth but not later during postnatal life controls the development of hypothalamic feeding circuits and sympathetic innervation of adipose tissues, promoting a better management of metabolism in adulthood.

Pulsars with the masses 2.14M⊙ and 2.27M⊙ as strange star candidates

Strange stars with maximal masses, more than the values of recently precisely measured masses of two radio pulsars: SRJ0740+6620, with the mass 2.14М⊙, and PSRJ2215+5135, with the mass 2.27М⊙, have been studied. For the examination of strange quark matter (SQM), the bag model, developed in Massachusetts Technological Institute was chosen. The observed bag model depends on vacuum pressure B, quark-gluon interaction constant αc, and strange quark mass ms. Since the transition to SQM state takes place at the energy density, not exceeding double density in atomic nuclei, neutron stars with small mass and configuration, consisting of SQM, form one family in the dependence curve of the mass M, of the equilibrium super-dense configurations, on the energy central density ρc (curve M(ρc)). The state equation of strange quark matter was studied when the vacuum pressure was constant. Groups of the values of these parameters were determined; their application in the state equation of SQM leads to the maximal mass of the equilibrium quark configurations Mmax, which are heavier than the aforementioned radio pulsars. For such configurations, the values of mass, radius, the entire number of baryons, red shift from the strange star surface were calculated, depending on the energy central density ρc. For each series with Mmax>2.14M⊙ and Mmax>2.27M⊙ the values of the mentioned integral parameters were calculated as well for super-dense configurations with 2.27and2.14 solar masses that were precisely determined from observations. According to the obtained state equations, these two radio pulsars can be the possible candidates for the strange stars.

Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior

Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.

Acute and Reversible Hypothalamic Symptoms in a Lateral Head Impact Mouse Model of Mild Traumatic Brain Injury.

Central autonomic and endocrine dysfunctions following traumatic brain injury (TBI) are believed to involve the hypothalamus; however, underlying mechanisms are unknown. Although chronic deficits might be caused by irreversible tissue damage, various neuroendocrine and autonomic symptoms are only observed transiently, suggesting they might result from a temporary alteration in the activity of hypothalamic neurons. We therefore examined if a mouse model of mild TBI could induce reversible autonomic phenotypes and cause acute changes in c-Fos expression within corresponding regions of the hypothalamus. Adult C57Bl/6 male mice were lightly anesthetized with isoflurane and subjected to TBI by lateral head impact using a Gothenburg impactor. Mice treated the same way, but without the head impact served as controls (shams). We monitored body weight and core body temperature by infrared thermography and performed immunohistochemistry against c-Fos in various regions of the hypothalamus. We determined that a projectile velocity of 9 m/s significantly delayed recovery from the anesthesia without inducing skull fractures and signs of discomfort disappeared within 3 h, as assessed by grimace scale. Compared with shams, TBI mice displayed a rapid decrease in core body temperature which resolved within 48 h. Daily body weight gain was also significantly lower in TBI mice on the day following injury but recovered thereafter. c-Fos analysis revealed a significantly higher density of c-Fos-positive cells in the paraventricular nucleus and a significantly lower density in the median preoptic nucleus and medial preoptic area. We conclude that mild TBI induced by a single lateral head impact in mice at 9 m/s produces acute and reversible symptoms associated with hypothalamic dysfunction accompanied by significant changes in c-Fos expression within relevant areas of the hypothalamus. These findings support the hypothesis that a temporary alteration of neuronal activity may underlie the expression of reversible central autonomic and neuroendocrine symptoms.

Differential effects of sleep deprivation on behavior and microglia in a brain-region-specific manner in young and aged male mice

Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD.

Survival, growth and digestive functions after exposure to nanodiamonds - Transgenerational effects beyond contact time in house cricket strains

The long-term exposure effects of nanodiamonds (NDs), spanning an organism's entire lifespan and continuing for subsequent generation, remain understudied. Most research has focused on evaluating their biological impacts on cell lines and selected organisms, typically over short exposure durations lasting hours or days. The study aimed to assess growth, mortality, and digestive functions in wild (H) and long-lived (D) strains of Acheta domesticus (Insecta: Orthoptera) after two-generational exposure to NDs in concentrations of 0.2 or 2 mg kg−1 of food, followed by their elimination in the third generation. NDs induced subtle stimulating effect that depended on the strain and generation. In the first generation, more such responses occurred in the H than in the D strain. In the first generation of H strain insects, contact with NDs increased survival, stimulated the growth of young larvae, and the activity of most digestive enzymes in mature adults. The same doses and exposure time did not cause similar effects in the D strain. In the first generation of D strain insects, survival and growth were unaffected by NDs, whereas, in the second generation, significant stimulation of those parameters was visible. Selection towards longevity appears to support higher resistance of the insects to exposure to additional stressor, at least in the first generation. The cessation of ND exposure in the third generation caused potentially harmful changes, which included, e.g., decreased survival probability in H strain insects, slowed growth of both strains, as well as changes in heterochromatin density and distribution in nuclei of the gut cells in both strains. Such a reaction may suggest the involvement of epigenetic inheritance mechanisms, which may become inadequate after the stress factor is removed.

Degeneration of olivospinal tract in the upper cervical spinal cord of multiple system atrophy patients: Reappraisal of Helweg's triangular tract.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA. Myelin staining revealed that 22 cords (22.7%) had small, bilateral, triangular-shaped tract degeneration in the boundary of the anterior and lateral funiculi, which appeared continuously from C1 to C5. The anatomical pathway of the degenerated tract was consistent with the description of the olivospinal tract provided by Helweg in 1888. The MSA patients showing degeneration of this tract were younger at disease onset (average: 56.4 ± 8.7 years, range: 42-74), and had longer disease duration (average: 10.1 ± 4.8 years, range: 2-25) and more severe olivopontocerebellar changes compared to other MSA patients. Quantitative analyses revealed that patients with olivospinal tract degeneration had a lower neuronal density in the inferior olivary nucleus compared to other patients. Microglial density in this tract was negatively correlated with the neuronal density in the inferior olivary nucleus. The densities of glial cytoplasmic inclusions in the inferior olivary nucleus and in the olivospinal tract were strongly correlated with each other. Neurologically healthy controls (n = 22) and disease controls with Lewy body disease (n = 30), amyotrophic lateral sclerosis (n = 30), and progressive supranuclear palsy (n = 30) did not present the olivospinal tract degeneration. Our results indicate an impairment of the neural connection between the inferior olivary nucleus and the spinal cord in MSA patients, which may develop in a descending manner.

Calorie restriction partially attenuates sickness behavior induced by viral mimetic poly I:C

Calorie restriction (CR) has been shown to extend the mean and maximum lifespan in both preclinical and clinical settings. We have previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and sickness behavior. CR also leads to reductions in pro-inflammatory and increases in anti-inflammatory profiles. LPS is a bacterial mimetic; however, few studies have explored this phenomenon utilizing a viral mimetic, such as polyinosinic:polycytidylic acid (poly I:C). Dose-dependently, poly I:C induced an increase in core body temperature (Tb), with the largest dose (5000 µg/kg) resulting in a 1.62 °C ( ± 0.23 °C) Tb increase at 7 h post-injection in ad libitum mice and was associated with reduced home-cage locomotor activity. We then investigated the effect of 50% CR for 28 days to attenuate fever and sickness behavior induced by a poly I:C (5000 µg/kg) viral immune challenge. CR resulted in the partial attenuation of fever and sickness behavior measures post-poly I:C. The freely fed, control mice demonstrated a 2.02 °C ( ± 0.22 °C) increase in Tb at 7 h post-injection compared to the CR poly I:C group which demonstrated an increase in Tb of 0.94 °C ( ± 0.27 °C). Locomotor patterns post-injection were different, CR mice displayed a reduction in activity during the light phase, and the control group displayed a reduction during the dark phase. CR moderately attenuated the neuroinflammatory response with a reduction in microglial density in the ventromedial nucleus of the hypothalamus. The fever and sickness behavior attenuation seen after CR may be driven by similar anti-inflammatory processes as after LPS; however, further investigation is required.

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects. Here we establish and validate a psilocybin microdose-like regimen in rats with repeated low doses of psilocybin administration at a dose derived from occupancy at rat brain 5-HT2A receptors in vivo. The rats tolerated the repeated low doses of psilocybin well and did not manifest signs of anhedonia, anxiety, or altered locomotor activity. There were no deficits in pre-pulse inhibition of the startle reflex, nor did the treatment downregulate or desensitize the 5-HT2A receptors. However, the repeated low doses of psilocybin imparted resilience against the stress of multiple subcutaneous injections, and reduced the frequency of self-grooming, a proxy for human compulsive actions, while also increasing 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin. Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.

Gluon Density in the Rescaling Model

The behavior of the gluon density in nuclei is investigated in the framework of the rescaling model.

Strong interactions between highly dynamic lamina-associated domains and the nuclear envelope stabilize the 3D architecture of Drosophila interphase chromatin

BackgroundInteractions among topologically associating domains (TADs), and between the nuclear envelope (NE) and lamina-associated domains (LADs) are expected to shape various aspects of three-dimensional (3D) chromatin structure and dynamics; however, relevant genome-wide experiments that may provide statistically significant conclusions remain difficult.ResultsWe have developed a coarse-grained dynamical model of D. melanogaster nuclei at TAD resolution that explicitly accounts for four distinct epigenetic classes of TADs and LAD–NE interactions. The model is parameterized to reproduce the experimental Hi-C map of the wild type (WT) nuclei; it describes time evolution of the chromatin over the G1 phase of the interphase. The simulations include an ensemble of nuclei, corresponding to the experimentally observed set of several possible mutual arrangements of chromosomal arms. The model is validated against multiple structural features of chromatin from several different experiments not used in model development. Predicted positioning of all LADs at the NE is highly dynamic—the same LAD can attach, detach and move far away from the NE multiple times during interphase. The probabilities of LADs to be in contact with the NE vary by an order of magnitude, despite all having the same affinity to the NE in the model. These probabilities are mostly determined by a highly variable local linear density of LADs along the genome, which also has the same strong effect on the predicted positioning of individual TADs -- higher probability of a TAD to be near NE is largely determined by a higher linear density of LADs surrounding this TAD. The distribution of LADs along the chromosome chains plays a notable role in maintaining a non-random average global structure of chromatin. Relatively high affinity of LADs to the NE in the WT nuclei substantially reduces sensitivity of the global radial chromatin distribution to variations in the strength of TAD–TAD interactions compared to the lamin depleted nuclei, where a small (0.5 kT) increase of cross-type TAD–TAD interactions doubles the chromatin density in the central nucleus region.ConclusionsA dynamical model of the entire fruit fly genome makes multiple genome-wide predictions of biological interest. The distribution of LADs along the chromatin chains affects their probabilities to be in contact with the NE and radial positioning of highly mobile TADs, playing a notable role in creating a non-random average global structure of the chromatin. We conjecture that an important role of attractive LAD–NE interactions is to stabilize global chromatin structure against inevitable cell-to-cell variations in TAD–TAD interactions.

The density of ambient black carbon retrieved by a new method: implications for cloud condensation nuclei prediction

Abstract. The effective density of black carbon (BC) is a crucial factor that is relevant to its aging degree and adds uncertainty in evaluating its climate effect. Here, we have developed a new method to retrieve the effective density of internally mixed BC in the atmosphere, combining field observations conducted from 15 November to 14 December 2016 in urban Beijing with the Köhler theory. The uncertainty in the retrieval method was evaluated to be within ±30 %, which was primarily caused by assumptions on both the hygroscopic parameter of organics and the proportional distribution of primary organic aerosols in different hygroscopic modes. Using the method, we find that the ambient internally mixed BC, accounting for 80 % ± 20 % of total BC aerosol particles, was retrieved with a campaign mean density of 1.1 ± 0.6 g cm−3 during the observed periods. The retrieved result was comparable with that reported in the literature. By applying a lower (0.14 g cm−3) and upper (2.1 g cm−3) limit of the retrieved BC density in the cloud condensation nuclei (CCN) number concentration (NCCN) estimation, we derived that the neglect of such variations in the BC density would lead to an uncertainty of −28 %–11 % in predicting NCCN at supersaturations of 0.23 % and 0.40 %. We also find that the NCCN was more sensitive to the variations in BC density when it was <1.0 g cm−3. This illustrates the necessity of accounting for the effect of BC density on CCN activity closer to source regions where the BC particles are mostly freshly emitted. The CCN closure was achieved when introducing the retrieved real-time BC density and mixing state. This study provides a unique way of utilizing field measurements to infer ambient BC density and highlights the importance of applying variable BC density values in models when predicting CCN and assessing its relevant climate effect.

Low-energy nuclear physics and global neutron star properties

We address the question of the role of low-energy nuclear physics data in constraining neutron star global properties, e.g., masses, radii, angular momentum, and tidal deformability, in the absence of a phase transition in dense matter. To do so, we assess the capacity of 415 relativistic mean field and nonrelativistic Skyrme-type interactions to reproduce the ground state binding energies, the charge radii, and the giant monopole resonances of a set of spherical nuclei. The interactions are classified according to their ability to describe these characteristics, and we show that a tight correlation between the symmetry energy and its slope is obtained provided that $N=Z$ and $N\ensuremath{\ne}Z$ nuclei are described with the same accuracy (mainly driven by the charge radius data). By additionally imposing the constraints from isobaric analog states and neutron skin radius in $^{208}\mathrm{Pb}$, we obtain the following estimates: ${E}_{\mathrm{sym},2}=31.8\ifmmode\pm\else\textpm\fi{}0.7$ MeV and ${L}_{\mathrm{sym},2}=58.1\ifmmode\pm\else\textpm\fi{}9.0$ MeV. We then analyze predictions of neutron star properties and we find that the $1.4{M}_{\ensuremath{\bigodot}}$ neutron star (NS) radius lies between 12 and 14 km for the ``better'' nuclear interactions. We show that (i) the better reproduction of low-energy nuclear physics data by the nuclear models only weakly impacts the global properties of canonical mass neutron stars and (ii) the experimental constraint on the symmetry energy is the most effective one for reducing the uncertainties in NS matter. However, since the density region where constraints are required are well above densities in finite nuclei, the largest uncertainty originates from the density dependence of the energy density functional (EDF), which remains largely unknown.

IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice

Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15-20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes.

Vitamin D supplementation combined with aerobic physical exercise restores the cell density in hypothalamic nuclei of rats exposed to monosodium glutamate.

In view of the increase in the prevalence of obesity and metabolic syndrome in childhood and adolescence, this study proposed the early and combined use of treatments to restore brain areas related to satiety. The vitamin D supplementation, aerobic exercise and the combination of these interventions on the structure of arcuate (ARC) and ventromedial (VMH) nuclei of hypothalamus were investigated in monosodium glutamate (MSG)-treated rats. Wistar rats were separated into five groups: Control group (CT); Obese group injected with MSG (OB); Obese group supplemented with vitamin D (OBvd); Obese group submitted to forced swimming training (OBexe) and Obese group treated with vitamin D supplementation and forced swimming training (OBvd+exe). In the OB group, the visceral fat weight was significantly higher, there was a reduction in the number of glial cells in the ARC nucleus and also in the number of neurons in the ARC and VMH nuclei. Aerobic exercise was able to reduce the visceral fat weight in the OBexe group. The combination of treatments used in the OBvd+exe group reversed the loss of neurons and glial cells produced by MSG in the ARC nucleus. All treated groups exhibited a higher number of neurons in VMH nucleus, but an increase in the glial cells were observed only in the OBexe and OBvd+exe groups. The effectiveness of obesity treatment can be favored through the early and combined use of vitamin D supplementation and aerobic exercise, since these therapies are able to restore brain nuclei involved in the control of food intake.

Thyroid Supplementation Reverses the Abnormal Social and Oxytocin Phenotype Produced by Developmental Exposure to PBDEs in a Sex‐Dependent Manner

Polybrominated diphenyl ethers (PBDEs) are endocrine‐disrupting chemicals (EDCs) that are widely used flame retardants added to common household products. In humans, PBDEs are associated with neurodevelopmental deficits including ones associated with social competence and learning. We have previously shown that PBDE‐exposed F1 female progeny display autism‐relevant characteristics such as deficient social novelty preference and social recognition memory (SRM), exaggerated repetitive behavior and deficient social odor discrimination (Kozlova et al 2021). In this study, we show that developmental exposure (via dam GD0‐PND21) to the PBDE mixture, DE‐71 (L‐DE‐71; 0.1 mg/kg/d), reduces oxytocin immunofluorescence density in the paraventricular nucleus of the hypothalamus (PVN) that is critical for social recognition memory in male and female F1 offspring relative to VEH/CON (0 mg/kg/d). One of the well characterized actions of PBDEs is disruption of the hypothalamo‐pituitary‐thyroid axis (HPT). Thyroid hormones (TH) are critical for nervous system development and regulate the transcription of oxytocin. We show for the first time, that L‐DE‐71 alters central thyroid hormone species (T2, rT3, T3, and T4) relative to VEH/CON in F1 offspring but with a different temporal pattern in males (PND30) and females (PND15) as measured using liquid chromatography‐tandem mass spectrometry. This coincides with reduced plasma T4 in PND15 male but not female offspring. Supplementation of pregnant dams with levothyroxine, a synthetic analogue of thyroxine (T4), during gestation and lactation (GD12‐PND21), increased plasma oxytocin in exposed dams. More importantly, supplementation normalized PBDE‐induced deficiency in social recognition memory test, and PVN oxytocin levels in exposed female but not male offspring. These changes are specific to social behavior as were no changes in passive avoidance memory. Interestingly, L‐DE‐71 female but not male F1 also receiving supplementation showed a significant increase in plasma T4. Maternal behavior (retrieval of PND4 pups) was significantly reduced by supplementation with 6‐propyl‐2‐thiouracil, a drug that blocks the production of thyroid hormone by thyroid gland, but not by DE‐71 nor DE‐71 plus levothyroxine supplementation. These results provide novel insight into neuroendocrine disruption of the central oxytocin system by maternal transfer of environmental pollutants and its possible contribution to neurodevelopmental disorders such as autism.

Synaptic pathology in multiple sclerosis: a role for Nogo-A signaling in astrocytes?

Synaptic pathology in multiple sclerosis: a role for Nogo-A signaling in astrocytes?

Maternal exercise and high-fat diet affect hypothalamic neural projections in rat offspring in a sex-specific manner

This study aimed to investigate the effect of maternal high-fat (HF) diet and exercise during gestation and lactation on hypothalamic neural projection development in the offspring. Pregnant Sprague-Dawley rats were fed a CHOW or HF diet during gestation and lactation, and further divided into two subgroups: voluntary exercised and sedentary. Offspring's brains and tissue were collected at weaning and 16 weeks of age. Maternal exercise downregulated dams’ body weight and food intake during lactation, but failed to normalize increased fat weight, plasma and milk leptin levels of HF dams at weaning. Maternal HF diet significantly increased offspring's body weight, adipose depots, plasma insulin, and leptin at weaning and had long-term effect on body weight of male offspring, while maternal exercise decreased offspring's body weight from 3 to 5 weeks of age in both sexes. At weaning, maternal exercise decreased αMSH fiber density and maternal HF diet impaired agouti-related peptide fiber density in the paraventricular nucleus of hypothalamus of male pups, while maternal HF diet disrupted αMSH fiber density in the paraventricular nucleus of hypothalamus of female pups. The impaired αMSH fiber density was consistent with reduced STAT3 signaling in the arcuate nucleus of hypothalamus, while the reduced agouti-related peptide fiber density was consistent with reduced ERK1/2 signaling in the arcuate nucleus of hypothalamus. The impaired hypothalamic projections were compensated in adulthood in both sexes. Our findings suggest that maternal HF diet and exercise exerts different effects on hypothalamic neural projections development through distinct signaling pathways in a sex-specific manner.

Neurite density imaging in amygdala nuclei reveals interindividual differences in neuroticism.

Neuroticism is known to have significant health implications. While previous research revealed that interindividual differences in the amygdala function are associated with interindividual differences in neuroticism, the impact of the amygdala’s structure and especially microstructure on variations in neuroticism remains unclear. Here, we present the first study using NODDI to examine the association between the in vivo microstructural architecture of the amygdala and neuroticism at the level of neurites. We, therefore, acquired brain images from 221 healthy participants using advanced multi‐shell diffusion‐weighted imaging. Because the amygdala comprises several nuclei, we, moreover, used a high‐resolution T1 image to automatically segment the amygdala into eight different nuclei. Neuroticism and its facets have been assessed using the NEO‐PI‐R. Finally, we associated neuroticism and its facets with the volume and microstructure of the amygdala nuclei. Statistical analysis revealed that lower neurite density in the lateral amygdala nucleus (La) was significantly associated with higher scores in depression, one of the six neuroticism facets. The La is the sensory relay of the amygdala, filtering incoming information based on previous experiences. Reduced neurite density and related changes in the dendritic structure of the La could impair its filtering function. This again might cause harmless sensory information to be misevaluated as threatening and lead to the altered amygdala responsivity as reported in previous studies investigating the functional correlates of neuroticism and neuroticism‐related disorders like depression.

Long-term consequences of peri-adolescent social isolation on social preference, anxiety-like behaviour, and vasopressin neural circuitry of male and female rats.

Social isolation during the juvenile and adolescent stages (peri-adolescent social isolation) can have long-term consequences for behavioural and neural development. Most of this research, however, has relied on data from males, and very few studies have included both sexes. The present study investigated the impact of peri-adolescent social isolation on social preference, anxiety-like behaviour, and vasopressin neural circuitry of male and female Long Evans rats. Rats were either housed alone for 3 weeks beginning at weaning (Isolated) or in groups (Group-housed). In adulthood, rats were tested in social preference, open field, marble burying, and light/dark box tests, and brains were processed for vasopressin immunohistochemistry. Isolated males exhibited a lower social preference score and spent more time in the light zone of the light/dark box than their group-housed counterparts. Isolated and Group-housed females did not differ in these measures. Peri-adolescent social isolation did not alter vasopressin fibre density in target areas known to influence social and anxiety-like behaviours (the lateral septum or lateral habenula), but increased fibre density in an output pathway of the circadian pacemaker (projections to the paraventricular nucleus of the thalamus); an effect detected across both sexes. A previously unreported sex difference was also detected for vasopressin fibre density in the paraventricular nucleus of the thalamus (females > males). These findings demonstrate long-term consequences of peri-adolescent social isolation on social preference, anxiety-like behaviour, and the circadian vasopressin pathway and suggest that socio-affective development of males is more vulnerable to social stressors during the juvenile and adolescent stages.