Chronic social defeat alters behaviors and neuronal activation in the brain of female Mongolian gerbils.

Chronic social defeat has been found to be stressful and to affect many aspects of the brain and behaviors in males. However, relatively little is known about its effects on females. In the present study, we examined the effects of repeated social defeat on social approach and anxiety-like behaviors as well as the neuronal activation in the brain of sexually naïve female Mongolian gerbils (Meriones unguiculatus). Our data indicate that repeated social defeats for 20 days reduced social approach and social investigation, but increased risk assessment or vigilance to an unfamiliar conspecific. Such social defeat experience also increased anxiety-like behavior and reduced locomotor activity. Using ΔFosB-immunoreactive (ΔFosB-ir) staining as a marker of neuronal activation in the brain, we found significant elevations by social defeat experience in the density of ΔFosB-ir stained neurons in several brain regions, including the prelimbic (PL) and infralimbic (IL) subnuclei of the prefrontal cortex (PFC), CA1 subfields (CA1) of the hippocampus, central subnuclei of the amygdala (CeA), the paraventricular nucleus (PVN), dorsomedial nucleus (DMH), and ventrolateral subdivision of the ventromedial nucleus (VMHvl) of the hypothalamus. As these brain regions have been implicated in social behaviors and stress responses, our data suggest that the specific patterns of neuronal activation in the brain may relate to the altered social and anxiety-like behaviors following chronic social defeat in female Mongolian gerbils.

Can the organization of health resource integration be analyzed in terms of the current state of unmet demand for health services? take the health needs of the elderly in a place in zhejiang province, china, as an example.

BACKGROUND: The aging of the population has made the health problems of the elderly increasingly prominent, and their health needs are increasing. Existing studies on health resource integration approaches are mostly incomplete in assessing the health service capacity from the perspective of the health service provider. OBJECTIVE: The unmet health needs of the elderly were sampled and analyzed from the perspective of health service demanders. To explore how to build an integrated medical organization structure to better meet the health needs of the elderly. METHODS: A whole-group sampling method was used to conduct a questionnaire survey of 1527 older adults in N district of H city, Zhejiang province, China, to cross-sectionally analyze their current status of unmet health needs. RESULTS: The survey and analysis found that the needs of the elderly in this community to obtain disease-related knowledge, rational exercise, a healthy diet, and access to health information were not met. There were more patients with chronic diseases, and the top three chronic disease prevalence rates were hypertension (40.2%), dyslipidemia (8.4), and diabetes (7%). Chronic disease co-morbidities accounted for 13.3%. CONCLUSION: The relatively independently set up health service system at the present stage in China can no longer fully meet the health needs of the elderly, and the health service providers should provide integrated and continuous health services to meet the needs of whole-cycle health management. Therefore, we believe that effectively integrating various health service providers in the region and building an integrated health service organization with general practitioners as the core may be a solution to the current situation of unmet health needs of the elderly.

The effects of coloring therapy on patients with generalized anxiety disorder.

Generalized anxiety disorder (GAD) has harmful effects on physical and mental health and quality of life. Coloring therapy has been reported to have a positive effect on improving patient anxiety and depression. But there are no reported clinical trials examining their effectiveness as a treatment for GAD. This study was planned to evaluate the effectiveness of coloring therapy combined with conventional therapy in improving anxiety, depression, and positive and negative emotions with GAD. This randomized controlled study comprising 88 GAD patients was selected for intervention in different wards. The control group (n = 45) was given conventional antianxiety medication and physical therapy, and the experimental group (n = 43) received coloring therapy combined with conventional therapy. The Self-Rating Depression Scale, Self-Rating Anxiety Scale (SAS), Hamilton Depression Scale, Hamilton Anxiety Scale (HAMA), and Positive and Negative Affect Scale were assessed in both groups before and 3 weeks after the intervention. After the intervention, there were statistical differences in intra- and inter-group comparisons of anxiety, depression, and positive and negative mood scales in the experimental and control groups (p < .05). The minus in anxiety/positive emotions pre- and postintervention in the experimental group was statistically significant compared to that in anxiety/positive emotions pre- and postintervention in the control group (HAMA: d = 1.45, 95% confidence interval [CI] (0.34, 2.57), p = .011; SAS: d = 3.87, 95% CI (1.73,6.00), p = .001; positive: d = 1.76, 95% CI (0.17, 3.34), p = .030). The minus in depressive/negative emotions pre- and postintervention in the experimental group was not statistically significant compared with that in depressive/negative emotions pre- and postintervention in the control group (p > .05). For GAD patients, adding coloring therapy based on conventional drug therapy and physical therapy can not only reduce depression and negative emotions but also have better effects on reducing anxiety and improving positive emotions than conventional therapy.

Amphetamine exposure alters behaviors, and neuronal and neurochemical activation in the brain of female prairie voles.

Previous studies have shown that 3-day d-amphetamine (AMPH) treatment effectively induced conditioned place preferences (CPP) and impaired pair bonding behaviors in prairie voles (Microtus ochrogaster). Using this established animal model and treatment regimen, we examined the effects of the demonstrated threshold rewarding dose of AMPH on various behaviors and their potential underlying neurochemical systems in the brain of female prairie voles. Our data show that 3-day AMPH injections (0.2 mg/kg/day) impaired social recognition and decreased depressive-like behavior in females without affecting their locomotion and anxiety-like behaviors. AMPH treatment also decreased neuronal activation indicated by the labeling of the early growth response protein 1 (Egr-1) as well as the number of neurons double-labeled for Egr-1 and corticotrophin-releasing hormone (CRH) in the dentate gyrus (DG) of the hippocampus and paraventricular nucleus of the hypothalamus (PVN) in the brain. Further, AMPH treatment decreased the number of neurons double-labeled for Egr-1 and tyrosine hydroxylase (TH) but did not affect oxytocinergic neurons in the PVN or cell proliferation and neurogenesis markers in the DG. These data not only demonstrate potential roles of the brain CRH and dopamine systems in mediating disrupted social recognition and depressive-like behaviors by AMPH in female prairie voles, but also further confirm the utility of the prairie vole model for studying interactions between psychostimulants and social behaviors.

Geniposide attenuates postischemic long-term potentiation via GluN2A.

N-Methyl-D-aspartate receptor (NMDAR)-induced antioxidation is a significant cause of neuronal injury after ischemic stroke. In a previous work, we verified the neuroprotective roles of geniposide during tMCAO in vivo. However, it remains unknown whether geniposide ameliorates injury to hippocampal neurons during Ischemic Long Term Potentiation (iLTP) induction in vitro. After induction of cells oxygen-glucose deprivation or hydrogen peroxide, the protection of geniposide evaluated by MTT assay and electrophysiological tests. In this study, we suggested neuronal cell apoptosis was attenuated by geniposide. Furthermore, field excitatory postsynaptic potentials (fEPSCs) following postischemic LTP were assessed by electrophysiological tests. Finally, we determined that medium and high doses of geniposide attenuated oxidative stress insult and improved iLTP. Importantly, these effects were abolished by cotreatment with geniposide and the GluN2A antagonist NVP. In contrast, the GluN2B inhibitor ifenprodil failed to have an effect. In conclusion, we suggest for the first time that treatment with geniposide can attenuate postischemic LTP induction in a concentration-dependent manner. We infer that GluN2A-containing NMDARs are involved in the neuroprotection induced by geniposide treatment in ischemia.

Population variation alters aggression-associated oxytocin and vasopressin expressions in brains of Brandt's voles in field conditions.

Density-dependent change in aggressive behavior contributes to the population regulation of many small rodents, but the underlying neurological mechanisms have not been examined in field conditions. We hypothesized that crowding stress and aggression-associated oxytocin (OT) and arginine vasopressin (AVP) in specific regions of the brain may be closely related to aggressive behaviors and population changes of small rodents. We analyzed the association of OT and AVP expression, aggressive behavior, and population density of Brandt's voles in 24 large semi-natural enclosures (0.48 ha each) in Inner Mongolia grassland. We tested the effects of population density on the OT/AVP system and aggressive behavior by experimentally manipulating populations of Brandt's voles in the grassland enclosures. High density was positively and significantly associated with more aggressive behavior, and increased expression of mRNA and protein of AVP and its receptor, but decreased expression of mRNA and protein of OT and its receptor in specific brain regions of the voles. Our study suggests that changes in OT/AVP expression are likely a result of the increased psychosocial stress that these voles experience during overcrowding, and thus the OT/AVP system can be used as indicators of density-dependent stressors in Brandt's voles.

Combined Treatment With H1 and H4 Receptor Antagonists Improves Th2 Inflammatory Responses in the Nasal Mucosa of Allergic Rhinitis Rats.

BACKGROUND: Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. OBJECTIVES: We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. METHODS: Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. RESULTS: The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. CONCLUSION: H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.

Density-induced social stress alters oxytocin and vasopressin activities in the brain of a small rodent species.

It is known that social stress could alter oxytocin (OT) and arginine-vasopressin (AVP) expression in specific regions of brains which regulate the aggressive behavior of small rodents, but the effects of density-induced social stress are still unknown. Brandt's voles (Lasiopodomys brandtii) are small herbivores in the grassland of China, but the underlying neurological mechanism of population regulation is still unknown. We tested the effects of housing density of Brandt's voles on OT/AVP system with physical contact (allowing aggression) and without physical contact (not allowing aggression) under laboratory conditions. Then, we tested the effects of paired-aggression (no density effect) of Brandt's voles on OT/AVP system under laboratory conditions. We hypothesized that high density would increase aggression among animals which would then increase AVP but reduce OT in brains of animals. Our results showed that high housing density induced more aggressive behavior. We found high-density-induced social stress (with or without physical contact) and direct aggression significantly increased expression of mRNA and protein of AVP and its receptor, but decreased expression of mRNA and protein of OT and its receptor in specific brain regions of voles. The results suggest that density-dependent change of OT/AVP systems may play a significant role in the population regulation of small rodents by altering density-dependent aggressive behavior.

Glycine attenuates cerebrovascular remodeling via glycine receptor alpha 2 and vascular endothelial growth factor receptor 2 after stroke.

As a dual-acting neurotransmitter, glycine plays critical roles in cerebral ischemia by activating both glycine receptors (GlyRs) and N-methyl-D-aspartate acid receptors (NMDARs). However, the involvement of glycine receptor alpha 2 (GlyRa2) in cerebral ischemia has not been explored. The objective of this study was to determine the mechanism of action of GlyRa2 in cerebrovascular remodeling. After induction of rat tMCAO, levels of the GLRA2 gene and GlyRa2 protein were examined using q-PCR, western blot, and immunohistochemical analyses. Blood-brain barrier permeability, and the presence of hemorrhage and arteriosclerosis were also analyzed. The underlying mechanism of vascular remodeling was examined using immunohistochemical and immunofluorescence analyses. Both the GLRA2 gene and GlyRa2 protein were altered sharply after stroke. GlyRa2 of vascular origin appears to play a protective role after glycine treatment for ischemia. Blockade of GlyRa2 by the addition of cyclothiazide was found to abolish previous improvements in cerebrovascular survival after glycine treatment for tMCAO in rats. GlyRa2-dependent neurovascular remodeling was found to be correlated with the vascular endothelial growth factor receptor 2 (VEGFR2) pathways. These results suggest that vascular-derived GlyRa2 protects against post-ischemic injury. Vascular protection via GlyRa2 is due to VEGFR2/pSTAT3 signaling.

Agonistic behaviors and neuronal activation in sexually naïve female Mongolian gerbils.

Agonistic interaction is important for establishing social hierarchy and determining access to limited resources. Although there are substantial studies investigating the neural mechanisms of aggressive or defensive behavior in male rodents, little attention has been paid to the mechanisms underlying agonistic behaviors in females. In the present study, we depicted patterns of agonistic behaviors in sexually naïve female Mongolian gerbils (Meriones unguiculatus) and examined the neuronal activation in the brain by Fos-immunoreactive (Fos-ir) staining. We found that the winner-loser relationship was established rapidly. Winners displayed higher levels of aggression, environmental exploration, scent marking, and self-grooming, but less defensive behavior, in comparison to losers. Several patterns of Fos-ir expression emerged following agonistic interactions. Winners had the number of Fos-ir cells in the ventrolateral subnucleus of the ventromedial hypothalamus (VMHvl) and dorsal periaqueductal grey (PAGd) more than the controls but less than the losers. Losers also had more Fos-ir cells in the paraventricular nucleus of the hypothalamus (PVN), anterior medial (BSTam) and anteriolateral (BSTal) subnuclei of the bed nucleus of the stria terminalis (BST), and the ventral subnucleus of the lateral septum (LSv), as well as less Fos-ir cells in the dentate gyrus of the hippocampus (DG), compared to the controls. In addition, the number of Fos-ir cells showed similar increases in the principal nucleus (BSTpr) and interfascicular nucleus (BSTif) of the BST and amygdala (AMYG) in both the winners and losers, compared to the controls. Together, these data illustrate the patterns of altered neuronal activation in a behavior-, social status-, and brain region-specific manner, implicating potential roles of the brain neural circuit in mediating agonistic interactions in female Mongolian gerbils.

Anti-complementary activity of a degraded sulfated heterogalactan from red alga Pyropia haitanensis.

A sulfated galactan LP-G2 was isolated and purified from red alga, Pyropia haitanensis. It was a branched polysaccharide with average molecular weight about 8381 Da, composed of Gal, Glc, GalA and Ara. The structure of LP-G2 was determined using IR and NMR spectroscopy. It was composed of →4)-ß-d-galactose→4)-α-l-galactose-6- sulfate segments, with ß-d-Glc and α-d-galactose unit substituted at the 6-position of α-l-galactose. Functional analysis showed that LP-G2 inhibited complement activation on both the classic and alternative pathways with CH50 value of 3.08 ± 0.25 mg/mL and AP50 value of 2.23 ± 0.20 mg/mL, respectively. Preliminary mechanism studies by using complement component depleted-sera indicated that LP-G2 selectively interacts with C1q, C2, C4 and C9. The results suggested that LP-G2 could be of potential benefits in treatment of the complement associated diseases.

Aggressive behavior and brain neuronal activation in sexually naïve male Mongolian gerbils.

Aggressive behavior plays an important role in animal's survival and reproductive success. Although there has been growing interests in studying neural mechanisms underlying aggressive behavior using traditional laboratory animal models, little is known about mechanisms controlling naturally occurring aggression in sexually naïve animals. In the present study, we characterized aggressive behavior displayed by sexually naïve male Mongolian gerbils (Meriones unguiculatus) and examined the subsequent neuronal activation in the brain measured by Fos-immunoreactive (Fos-ir) staining. We found that resident males initiated attacks and showed intense levels of aggression (including chase, bite, offensive sideway, lunge and on-top) towards a conspecific male intruder. Furthermore, attacks from the resident males towards the intruder produced a nonrandom distribution of bites, with the most on the rump, flank, back and tail and few on the limbs, ventrum and head. In contrast, control males that were exposed to a woodblock (control for novelty) never attacked the woodblock and showed higher levels of object/environmental investigation. Male gerbils exposed to an intruder had significantly higher levels of Fos-ir density in the medial (MeA) and anterior cortical (ACo) subnuclei of the amygdala, principal nucleus (BSTpr) and interfascicular nucleus (BSTif) of the bed nucleus of the stria terminalis, ventrolateral subdivision of the ventromedial hypothalamus (VMHvl), and paraventricular nucleus of the hypothalamus (PVN), compared to control males. Together, our results indicate that sexually naïve, group housed male gerbils naturally display aggression towards conspecific strangers, and such aggressive behavior is associated with special patterns of neuronal activation in the brain.

The degraded polysaccharide from Pyropia haitanensis represses amyloid beta peptide-induced neurotoxicity and memory in vivo.

An antioxidant polysaccharide, porphyran, from red algae Pyropia haitanensis, is introduced as a protective agent against neurotoxicity-induced amyloid ß peptide (Aß) of Alzheimer's disease (AD) mice. Then the activity of acetylcholinesterase (AChE) and choline acetyltransferase (CHAT) in the cortical and hippocampal tissue were examined by colorimetric method. Results showed that porphyran significantly ameliorated the learning and memory impairment induced by Aß1-40. Biochemical analysis showed that porphyran increased ChAT activity and decreased AChE activity in the cortical and hippocampal tissue. The mechanism may be related with the increase of cerebral acetylcholine content. Porphyran has a potential of developing anti-aging drug.

Downregulations of placental fatty acid transporters during cadmium-induced fetal growth restriction.

Cadmium (Cd) is one of the environmental pollutants, which has multiple toxic effects on fetuses and placentas. Placental fatty acid (FA) uptake and transport are critical for the fetal and placental development. We aimed to analyze the triglyceride (TG) level, the expression patterns of several key genes involved in FA uptake and transport, and the molecular mechanisms for the altered gene expressions in placentas in response to Cd treatment. Our results showed that the placental TG level was significantly decreased in the Cd-exposed placentas. Fatty acid transporting protein 1 (FATP1), FATP6 and fatty acid binding protein 3 (FABP3) were significantly down-regulated in the placentas from Cd-exposed mice. The expression level of phospho-p38 MAPK was increased by Cd treatment, while the protein level of total p38 MAPK remained unchanged. The expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and the hypoxia-inducible factor-1α (HIF-1α) were significantly decreased in the Cd-exposed placentas. The methylation levels of the promoter regions of FATP1, FATP6 and FABP3 showed no significant differences between the treatment and control groups. In addition, the circulating non-esterified fatty acid (NEFA), total cholesterol (TC), and TG levels were not decreased in the maternal serum from the Cd-exposed mice. Therefore, our results suggest Cd exposure dose not reduce the maternal FA supply, but reduces the placental TG level. Cd treatment also downregulates the placental expressions of FATP1, FATP6 and FABP3, respectively associated with p38-MAPK, p38 MAPK/PPAR-γ and HIF-1α pathways.

Effect of sulfated galactan from Porphyra haitanensis on H2O2-induced premature senescence in WI-38 cells.

Porphyran sulfated galactan extracted from red algae Porphyra haitanensis is a sulfated polysaccharide, which possesses excellent activities. In the present study, WI-38 cells were treated with H2O2 to induce premature senescence and then the protection of porphyran against aging in vitro and associated molecular mechanisms were investigated. The protection occurred in a dose-dependent manner, offering an optimal efficacy starting at 10µg/mL. The proportion of SA-ß-gal positive cells in porphyran group decreases from 53% to 23% in the cultures at 30 PDs. Porphyran has been detected specifically reducing SAHF-like foci formation in senescent cells. In addition, porphyran significantly affected the p53-p21 pathways in H2O2-treated WI-38 cells. Our data suggest the promising role of porphyran as an attractive and bio-safe agent with the potential to retard senescence and attenuate senescence-related diseases.

Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory.

Adult neurogenesis, defined here as progenitor cell division generating functionally integrated neurons in the adult brain, occurs within the hippocampus of numerous mammalian species including humans. The present review details various endogenous (e.g., neurotransmitters) and environmental (e.g., physical exercise) factors that have been shown to influence hippocampal adult neurogenesis. In addition, the potential involvement of adult-generated neurons in naturally-occurring spatial learning behavior is discussed by summarizing the literature focusing on traditional animal models (e.g., rats and mice), non-traditional animal models (e.g., tree shrews), as well as natural populations (e.g., chickadees and Siberian chipmunk).

Species differences in the immunoreactive expression of oxytocin, vasopressin, tyrosine hydroxylase and estrogen receptor alpha in the brain of Mongolian gerbils (Meriones unguiculatus) and Chinese striped hamsters (Cricetulus barabensis).

Species differences in neurochemical expression and activity in the brain may play an important role in species-specific patterns of social behavior. In the present study, we used immunoreactive (ir) labeling to compare the regional density of cells containing oxytocin (OT), vasopressin (AVP), tyrosine hydroxylase (TH), or estrogen receptor alpha (ERα) staining in the brains of social Mongolian gerbils (Meriones unguiculatus) and solitary Chinese striped hamsters (Cricetulus barabensis). Multiple region- and neurochemical-specific species differences were found. In the anterior hypothalamus (AH), Mongolian gerbils had higher densities of AVP-ir and ERα-ir cells than Chinese striped hamsters. In the lateral hypothalamus (LH), Mongolian gerbils also had higher densities of AVP-ir and TH-ir cells, but a lower density of OT-ir cells, than Chinese striped hamsters. Furthermore, in the anterior nucleus of the medial preoptic area (MPOAa), Mongolian gerbils had higher densities of OT-ir and AVP-ir cells than Chinese striped hamsters, and an opposite pattern was found in the posterior nucleus of the MPOA (MPOAp). Some sex differences were also observed. Females of both species had higher densities of TH-ir cells in the MPOAa and of OT-ir cells in the intermediate nucleus of the MPOA (MPOAi) than males. Given the role of these neurochemicals in social behaviors, our data provide additional evidence to support the notion that species-specific patterns of neurochemical expression in the brain may be involved in species differences in social behaviors associated with different life strategies.

Agonistic encounters and brain activation in dominant and subordinate male greater long-tailed hamsters.

During an agonistic encounter test, dominant male greater long-tailed hamsters (Tscheskia triton) initiated attacks sooner and displayed higher levels of aggression and flank marking behavior than their subordinate counterparts. Accordingly, subordinate males exhibited more defensive behavior than dominant ones. Specific patterns of neuronal activation, measured by Fos-immunoreactive staining (Fos-ir), were found in the hamster brain following agonistic interactions. Increased Fos-ir was observed in the bed nucleus of the stria terminalis (BST), ventromedial hypothalamus (VMH), and medial (MeA) and anterior cortical (ACo) nuclei of the amygdala (AMYG) in both dominant and subordinate males. In contrast, dominant males had significantly higher Fos-ir densities in the medial preoptic area (MPOA) than subordinate males, whereas subordinate males expressed higher densities of Fos-ir in the anterior hypothalamus (AH) and central nucleus of the amygdala (CeA). Additionally, Fos-ir levels in the MPOA were significantly correlated with aggression and Fos-ir levels in the AH and CeA were correlated with defensive behavior. Together, our data indicate distinct patterns of neuronal activation associated with agonistic encounters in a behavior-specific manner in male greater long-tailed hamsters.

Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles.

Stressful social experiences early in life, such as maternal separation and social isolation, have enduring effects on the development of the brain and behavior. In the present study in socially monogamous male prairie voles (Microtus ochrogaster), we found that following 6 weeks of social isolation after weaning males spent more time in the closed arms and less time in the open arms during an elevated plus maze (EPM) test, moved more frequently from central to peripheral squares in an open field test, and diminished their preferences for the empty chamber during a two-chamber affiliation test, compared to control males that were housed with siblings. This increased behavioral anxiety in socially isolated males was also associated with enhanced mRNA expression for vasopressin (AVP), oxytocin (OT), corticotrophin releasing factor (CRF), and tyrosine hydroxylase (TH) in the paraventricular nucleus of the hypothalamus (PVN). Together, these data illustrate the importance of the post-weaning social environment on anxiety-related behavior and suggest a potential role of neurochemical systems in the PVN in the regulation of this behavior.