The molecular determinants of a universal prion acceptor.

In prion diseases, the species barrier limits the transmission of prions from one species to another. However, cross-species prion transmission is remarkably efficient in bank voles, and this phenomenon is mediated by the bank vole prion protein (BVPrP). The molecular determinants of BVPrP's ability to function as a universal prion acceptor remain incompletely defined. Building on our finding that cultured cells expressing BVPrP can replicate both mouse and hamster prion strains, we systematically identified key residues in BVPrP that permit cross-species prion replication. We found that residues N155 and N170 of BVPrP, which are absent in mouse PrP but present in hamster PrP, are critical for cross-species prion replication. Additionally, BVPrP residues V112, I139, and M205, which are absent in hamster PrP but present in mouse PrP, are also required to enable replication of both mouse and hamster prions. Unexpectedly, we found that residues E227 and S230 near the C-terminus of BVPrP severely restrict prion accumulation following cross-species prion challenge, suggesting that they may have evolved to counteract the inherent propensity of BVPrP to misfold. PrP variants with an enhanced ability to replicate both mouse and hamster prions displayed accelerated spontaneous aggregation kinetics in vitro. These findings suggest that BVPrP's unusual properties are governed by a key set of amino acids and that the enhanced misfolding propensity of BVPrP may enable cross-species prion replication.

Improvement of nonsurgical artificial insemination with cryopreserved spermatozoa in Alexandromys montebelli, Japanese grass vole.

Microtus genus is the herbivorous animal with multiple stomachs, and some of them possess a mating system similar to human and thereby has been expected as a model animal for the large herbivory and human mating system model, respectively. Thus, it is significant to maintain Microtus as an animal genetic resource. We have studied the establishment of assisted reproductive technologies in Alexandromys. montebelli (formerly as Microtus motebelli: A. motebelli), and here, we investigated the effects of hypotaurine treatment to frozen-thawed (FT) spermatozoa and modified timing of nonsurgical artificial insemination (AI) on the number of offspring. As the results, regardless of without or with hypotaurine treatment, when the timing of nonsurgical AI was made closer to the estimated ovulation time (at 7-9 h post coitus), the total number of offspring derived from FT spermatozoa (27 and 28 pups, respectively) increased compared with AI at 4-6 h (five and six pups, respectively) and was equivalent to those of fresh spermatozoa (43 pups) or natural mating (33 pups). These results will lead to further dissemination of nonsurgical AI and could support the "3R principle," which is the standard philosophy of animal experiment because the procedure declines the stress and the recipient can be used repeatedly.

Distinct medial amygdala oxytocin receptor neurons projections respectively control consolation or aggression in male mandarin voles.

The individuals often show consolation to distressed companions or show aggression to the intruders. The circuit mechanisms underlying switching between consolation and aggression remain unclear. In the present study, using male mandarin voles, we identified that two distinct subtypes of oxytocin receptor (OXTR) neurons in the medial amygdala (MeA) projecting to the anterior insula (AI) and ventrolateral aspect of ventromedial hypothalamus (VMHvl) response differently to stressed siblings or unfamiliar intruders using c-Fos or calcium recording. Oxytocin release and activities of PVN neurons projecting to MeA increased upon consoling and attacking. OXTR antagonist injection to the MeA reduced consoling and attacking. Apoptosis, optogenetic or pharmacogenetic manipulation of these two populations of neurons altered behavioral responses to these two social stimuli respectively. Here, we show that two subtypes of OXTR neurons in the MeA projecting to the AI or VMHvl causally control consolation or aggression that may underlie switch between consolation and aggression.

Regulatory mechanisms of Capillaria hepatica infection on Brandt's Vole (Lasiopodomys brandtii) population.

Parasite infection not only triggers the immune response of the host but also potentially affects the reproductive status, thereby influencing the population size. Therefore, understanding the impact of parasite infection on host immune and reproductive systems has long been an important issue in ecological research. To address this, we conducted field surveys (2021-2023) to investigate Capillaria hepatica infection status in Brandt's vole (Lasiopodomys brandtii) and performed controlled experiments in semi-natural enclosures and indoor laboratories. The results showed a negative correlation between the population size of Brandt's vole and the infection rate. To further explore the regulatory mechanisms, transcriptomic and proteomic analyses were performed on the infected BALB/c mice. The study found that post-infection with Capillaria hepatica, up-regulated genes and proteins in the mice liver were primarily associated with immune functions, while down-regulated genes and proteins were related to metabolic functions such as retinol metabolism. Through validation experiments supplementing retinol to the host infected with Capillaria hepatica, it was found that infection with Capillaria hepatica leads to a decrease in systemic available retinol levels, disrupting the expression of the hypothalamic-pituitary-gonadal (HPG) axis hormones, affecting the expression of CYP17A1, thereby regulating testosterone secretion related to spermatogenesis. This process results in abnormal spermatogenesis in the testes, thereby impacting the reproductive capacity of mice. This suggests that Capillaria hepatica regulates resource allocation in hosts, striking a "trade-off" between reproduction and survival, thereby exerting control over population size. These discoveries are crucial for comprehending the interaction between Capillaria hepatica and hosts, as well as their impacts on host reproduction and immune systems, and provide a scientific basis for controlling the transmission of Capillaria hepatica.

Convergent generation of atypical prions in knockin mouse models of genetic prion disease.

Most cases of human prion disease arise due to spontaneous misfolding of WT or mutant prion protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether spontaneous prion generation can occur within the mouse lifespan in the absence of protein overexpression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knockin mice that express the misfolding-prone bank vole prion protein (BVPrP). While mice expressing WT BVPrP (I109 variant) remained free from neurological disease, a subset of mice expressing BVPrP with mutations (D178N or E200K) causing genetic prion disease developed progressive neurological illness. Brains from spontaneously ill knockin mice contained prion disease-specific neuropathological changes as well as atypical protease-resistant BVPrP. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP-knockin mice exhibited prion seeding activity and transmitted disease to mice expressing WT BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical before and after transmission, suggesting that both mutations guide the formation of a similar atypical prion strain. These findings imply that knockin mice expressing mutant BVPrP spontaneously develop a bona fide prion disease and that mutations causing prion diseases may share a uniform initial mechanism of action.

Sex-Specific Impacts of Early Life Sleep Disruption: Ethanol Seeking, Social Interaction, and Anxiety Are Differentially Altered in Adolescent Prairie Voles.

Early life sleep is important for neuronal development. Using the highly social prairie vole rodent model, we have previously reported that early life sleep disruption (ELSD) during the preweaning period results in interference with social bonding and increases ethanol consumption following a stressor in adulthood. Furthermore, ELSD increases parvalbumin expression and reduces glutamatergic neurotransmission in cortical regions in adult prairie voles. To understand the impact of ELSD on the lifespan, an examination of an earlier time in life is necessary. The aim of the present study was to examine behavioral outcomes of ELSD on adolescent prairie voles. Given the known effects of ELSD on development of neuronal systems involved in mood and social motivation, we hypothesized that anxiety, risk, and reward-related behaviors would be impacted by ELSD in adolescent prairie voles. We report that both male and female adolescent prairie voles that experienced ELSD showed heightened anxiety-like behavior compared to age-matched controls (CONs) as measured by a light-dark box. Additionally, both male and female ELSD voles showed reductions in both ethanol preference and consumption, and affiliative behavior compared to CONs. These results suggest that adolescent prairie voles of both sexes experience heightened anxiety-like behavior and reduced reward-seeking behaviors after ELSD. These results further suggest that early life sleep is critically important for neurotypical behaviors in adolescence.

Paternal absence and increased caregiving independently and interactively shape the development of male prairie voles at subadult and adult life stages.

The influence of maternal caregiving is a powerful force on offspring development. The absence of a father during early life in biparental species also has profound implications for offspring development, although it is far less studied than maternal influences. Moreover, we have limited understanding of the interactive forces that maternal and paternal caregiving impart on offspring. We investigated if behaviorally upregulating maternal care compensates for paternal absence on prairie vole (Microtus ochrogaster) pup development. We used an established handling manipulation to increase levels of caregiving in father-absent and biparental families, and later measured male offspring behavioral outcomes at sub-adulthood and adulthood. Male offspring raised without fathers were more prosocial (or possibly less socially anxious) than those raised biparentally. Defensive behavior and responses to contextual novelty were also influenced by the absence of fathers, but only in adulthood. Offensive aggression and movement in the open field test changed as a function of life-stage but not parental exposure. Notably, adult pair bonding was not impacted by our manipulations. Boosting parental care produced males that moved more in the open field test. Parental handling also increased oxytocin immunoreactive cells within the supraoptic nucleus of the hypothalamus (SON), and in the paraventricular nucleus (PVN) of biparentally-reared males. We found no differences in vasopressinergic cell groups. We conclude that male prairie voles are contextually sensitive to the absence of fathers and caregiving intensity. Our study highlights the importance of considering the ways early experiences synergistically shape offspring behavioral and neural phenotypes across the lifespan.

Trophic fate and biomagnification of organic micropollutants from staple food to a specialized predator.

The environmental burden of organic micropollutants has been shown in aquatic ecosystems, while trophic fate of many compounds in terrestrial food chains remains highly elusive. We therefore studied concentrations of 108 organic micropollutants in a common European mammal, the bank vole (Clethrionomys glareolus), and 82 of the compounds in a specialized predator, Tengmalm's owl (Aegolius funereus) relying to >90 % on voles as its prey. We studied compounds in whole voles (n = 19), pools of 4-8 bank voles (npools = 4), owl blood (n = 10) and in owl eggs (n = 10) in two regions in Sweden. For comparison, we also included previously published data on 23 PFAS (per- and polyfluoroalkyl substances) in bank vole liver (npools = 4) from the same regions. In voles, concentrations of the organic micropollutants caffeine (maxIndividual 220 ng/g ww) and DEET (N,N-diethyl-m-toluamide) (maxPool 150 ng/g ww) were 2-200 times higher in voles relative to owl blood and eggs. Conversely, concentrations of nicotine, oxazepam, salicylic acid, and tributyl citrate acetate were 1.3-440 times higher in owls. Several PFAS showed biomagnification in owls as revealed by maximum biomagnification factors (BMFs); PFNA (perfluorononanoate) BMF = 5.6, PFTeDA (perfluorotetradecanoic acid) BMF = 5.9, and PFOS (perfluorooctane sulfonate) BMF = 6.1. Concentrations of organic micropollutants, alongside calculated BMFs, and Tengmalm's owl's heavy reliance on bank vole as staple food, suggest, despite small sample size and potential spatio-temporal mismatch, accumulation of PFAS (especially PFNA, PFTeDA, and PFOS) in owls and biomagnification along the food chain. Concentrations of PFAS in owl eggs (e.g., 21 ng/g ww PFOS) highlight the likely pivotal role of maternal transfer in contaminant exposure for avian embryos. These concentrations are also of concern considering that certain predators frequently consume owl eggs, potentially leading to additional biomagnification of PFAS with yet undetermined consequences for ecosystem health.

Molecular evolution of Hokkaido virus, a genotype of Orthohantavirus puumalaense, among Myodes rodents.

Viruses in the genus Orthohantavirus within the family Hantaviridae cause human hantavirus infections and represent a threat to public health. Hokkaido virus (HOKV), a genotype of Orthohantavirus puumalaense (Puumala virus; PUUV), was first identified in Tobetsu, Hokkaido, Japan. Although it is genetically related to the prototype of PUUV, the evolutionary pathway of HOKV is unclear. We conducted a field survey in a forest in Tobetsu in 2022 and captured 44 rodents. Complete coding genome sequences of HOKVs were obtained from five viral-RNA-positive rodents (four Myodes rufocanus bedfordiae and one Apodemus speciosus). Phylogenetic analysis revealed a close relationship between the phylogenies and geographical origins of M. rufocanus-related orthohantaviruses. Comparison of the phylogenetic trees of the S segments of orthohantaviruses and the cytochrome b genes of Myodes species suggested that Myodes-related orthohantaviruses evolved in Myodes rodent species as a result of genetic isolation and host switching.

Genetic admixture drives climate adaptation in the bank vole.

Genetic admixture introduces new variants at relatively high frequencies, potentially aiding rapid responses to environmental changes. Here, we evaluate its role in adaptive variation related to climatic conditions in bank voles (Clethrionomys glareolus) in Britain, using whole-genome data. Our results reveal loci showing excess ancestry from one of the two postglacial colonist populations inconsistent with overall admixture patterns. Notably, loci associated with climate adaptation exhibit disproportionate amounts of excess ancestry, highlighting the impact of admixture between colonist populations on local adaptation. The results suggest strong and localized selection on climate-adaptive loci, as indicated by steep clines and/or shifted cline centres, during population replacement. A subset, including a haemoglobin gene, is associated with oxidative stress responses, underscoring a role of oxidative stress in local adaptation. Our study highlights the important contribution of admixture during secondary contact between populations from distinct climatic refugia enriching adaptive diversity. Understanding these dynamics is crucial for predicting future adaptive capacity to anthropogenic climate change.

Effects of oxytocin receptor agonism on acquisition and expression of pair bonding in male prairie voles.

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.

Genome-wide relaxation of selection and the evolution of the island syndrome in Orkney voles.

Island populations often experience different ecological and demographic conditions than their counterparts on the continent, resulting in divergent evolutionary forces affecting their genomes. Random genetic drift and selection both may leave their imprints on island populations, although the relative impact depends strongly on the specific conditions. Here we address their contributions to the island syndrome in a rodent with an unusually clear history of isolation. Common voles (Microtus arvalis) were introduced by humans on the Orkney archipelago north of Scotland >5000 years ago and rapidly evolved to exceptionally large size. Our analyses show that the genomes of Orkney voles were dominated by genetic drift, with extremely low diversity, variable Tajima's D, and very high divergence from continental conspecifics. Increased d N/d S ratios over a wide range of genes in Orkney voles indicated genome-wide relaxation of purifying selection. We found evidence of hard sweeps on key genes of the lipid metabolism pathway only in continental voles. The marked increase of body size in Orkney-a typical phenomenon of the island syndrome-may thus be associated to the relaxation of positive selection on genes related to this pathway. On the other hand, a hard sweep on immune genes of Orkney voles likely reflects the divergent ecological conditions and possibly the history of human introduction. The long-term isolated Orkney voles show that adaptive changes may still impact the evolutionary trajectories of such populations despite the pervasive consequences of genetic drift at the genome level.

Epigenetic aging studies of pair bonding in prairie voles.

The quality of romantic relationships can predict health consequences related to aging. DNA methylation-based biomarkers of aging accurately estimate chronological age. We developed several highly accurate epigenetic aging clocks, based on highly conserved mammalian CpGs, for the socially monogamous prairie vole (Microtus ochrogaster). In addition, our dual-species human-vole clock accurately measured relative age and illustrates high species conservation of epigenetic aging effects. Next, we assessed how pair bonding impacts epigenetic aging. We did not find evidence that pair-bonded voles exhibit accelerated or decelerated epigenetic aging effects in blood, ear, liver, or brain tissue. Our epigenome wide association study identified CpGs in five genes strongly associated with pair bonding: Foxp4, Phf2, Mms22l, Foxb1, and Eif1ad. Overall, we present accurate DNA methylation-based estimators of age for a species of great interest to researchers studying monogamy in animals. We did not find any evidence that sex-naive animals age differently from pair-bonded animals.

Identification of spontaneous age-related cataract in Microtus fortis. / ä¸œæ–¹ç”°é¼ è‡ªå‘æ€§å¹´é¾„ç›¸å ³æ€§ç™½å† éšœçš„é‰´å®š.

OBJECTIVES: Age-related cataract is the most common type of adult cataract and a leading cause of blindness. Currently, there are few reports on the establishment of animal models for age-related cataract. During the experimental breeding of Microtus fortis (M. fortis), we first observed that M. fortis aged 12 to 15 months could naturally develop cataracts. This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M. fortis. METHODS: The 12-month-old healthy M. fortis were served as a control group and 12-month-old cataractous M. fortis were served as an experimental group. The lens transparency was observed using the slit-lamp biomicroscope. Hematoxylin and eosin staining was used to detect pathological changes in the lens. Biochemical detection methods were applied to detect blood routine, blood glucose levels, the serum activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in both groups. Finally, real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. RESULTS: Compared with the control group, the lens of cataract M. fortis showed severely visible opacity, the structure of lens was destroyed seriously, and some pathological damage, such as swelling, degeneration/necrosis, calcification, hyperplasia, and fiber liquefaction were found in lens epithelial cells (LECs). The fibrous structure was disorganized and irregularly distributed with morgagnian globules (MGs) aggregated in the degenerated lens fibers. There was no statistically significant difference in blood glucose levels between the experimental and control groups (P>0.05). However, white blood cell (WBC) count (P<0.05), lymphocyte count (P<0.01), and lymphocyte ratio (P<0.05) were significantly decreased, while neutrophil percentage (P<0.05) and monocyte ratio (P<0.01) were significantly increased. The serum activities of SOD and GSH-Px (both P<0.05) were both reduced. The mRNAs of cataract-related genes, including CRYAA, CRYBA1, CRYBB3, Bsfp1, GJA3, CRYBA2, MIP, HspB1, DNase2B, and GJA8, were significantly downregultaed in the lenses of the experimental group (all P<0.05). CONCLUSIONS: There are significant differences in lens pathological changes, peroxidase levels, and cataract-related gene expression between cataract and healthy M. fortis. The developed cataract spontaneously in M. fortis is closely related to age, the cataract M. fortis might be an ideal animal model for the research of age-related cataract.

The central oxytocinergic system of the prairie vole.

Oxytocin (OXT) is a peptide hormone and a neuropeptide that regulates various peripheral physiological processes and modulates behavioral responses in the central nervous system. While the humoral release occurs from the axons arriving at the median eminence, the neuropeptide is also released from oxytocinergic cell axons in various brain structures that contain its receptor, and from their dendrites in hypothalamic nuclei and potentially into the cerebrospinal fluid (CSF). Understanding oxytocin's complex functions requires the knowledge on patterns of oxytocinergic projections in relationship to its receptor (OXTR). This study provides the first comprehensive examination of the oxytocinergic system in the prairie vole (Microtus ochrogaster), an animal exhibiting social behaviors that mirror human social behaviors linked to oxytocinergic functioning. Using light and electron microscopy, we characterized the neuroanatomy of the oxytocinergic system in this species. OXT+ cell bodies were found primarily in the hypothalamus, and axons were densest in subcortical regions. Examination of the OXT+ fibers and their relationship to oxytocin receptor transcripts (Oxtr) revealed that except for some subcortical structures, the presence of axons was not correlated with the amount of Oxtr across the brain. Of particular interest, the cerebral cortex that had high expression of Oxtr transcripts contained little to no fibers. Electron microscopy is used to quantify dense cored vesicles (DCV) in OXT+ axons and to identify potential axonal release sites. The ependymal cells that line the ventricles were frequently permissive of DCV-containing OXT+ dendrites reaching the third ventricle. Our results highlight a mechanism in which oxytocin is released directly into the ventricles and circulates throughout the ventricular system, may serve as the primary source for oxytocin that binds to OXTR in the cerebral cortex.

Effect of tannic acid on adiponectin and gonads in male Brandt's voles (Lasiopodomys brandtii).

Adiponectin regulates steroid production and influences gonadal development. This study examined the effects of tannic acid (TA) on the adiponectin levels and gonads of male Brandt's voles. Male Brandt's voles aged 90 d were randomly separated into three groups: a control group (provided distilled water), a group given 600 mg∙kg-1 TA, and a group that received 1200 mg∙kg-1 TA (continuous gavage for 18 d). In this study, we examined the effects of TA on the adiponectin, antioxidant, and inflammatory levels in the testes. Furthermore, we examined the expression of important regulatory elements that influence adiponectin expression and glucose utilisation. In addition, the body weight, reproductive organ weight, and testicular shape were assessed. Our study observed that TA treatment increased serum adiponectin levels, DsbA-L and Ero1-Lα transcription levels, and AdipoR1, AMPK, GLUT1, and MCT4 expression levels in testicular tissue. TA enhanced pyruvate and lactic acid levels in the testicular tissue, boosted catalase activity, and reduced MDA concentrations. TA reduced the release of inflammatory factors in the testicular tissues of male Brandt's voles. TA increased the inner diameter of the seminiferous tubules. In conclusion, TA appears to stimulate adiponectin secretion and gonadal growth in male Brandt's voles while acting as an antioxidant and anti-inflammatory agent.

Morphological observation, molecular identification and evolutionary analysis of Hydatigera kamiyai found in Neodon fuscus from the Qinghai-Tibetan plateau.

Hydatigera kamiyai (H. kamiyai) is a new species within Hydatigera that has recently been resurrected. Voles and cats are hosts of H. kamiyai and have a certain impact on its health and economy. Moreover, the Qinghai-Tibetan plateau (QTP) is a research hotspot representing Earth's biodiversity, as its unique geographical environment and climatic conditions support the growth of a variety of mammals and provide favorable conditions for various parasites to complete their life history. The aim of this study was to reveal the phylogenetic relationships and divergence times of H. kamiyai strains isolated from Neodon fuscus on the QTP using morphological and molecular methods. In this study, we morphologically observed H. kamiyai and sequenced the whole mitochondrial genome. Then, we constructed phylogenetic trees with the maximum likelihood (ML) and Bayesian inference (BI) methods. The GTR alternative model was selected for divergence time analysis. These data demonstrated that the results were consistent with the general morphological characteristics of Hydatigera. The whole genome of H. kamiyai was 13,822 bp in size, and the A + T content (73%) was greater than the G + C content (27%). The Ka/Ks values were all <1, indicating that all 13 protein-coding genes (13 PCGs) underwent purifying selection during the process of evolution. The phylogenetic tree generated based on the 13 PCGs, cytochrom oxidase subunit I (COI), 18S rRNA and 28S rRNA revealed close phylogenetic relationships between H. kamiyai and Hydatigera, with high node support for the relationship. The divergence time based on 13 PCGs indicated that H. kamiyai diverged approximately 11.3 million years ago (Mya) in the Miocene. Interestingly, it diverged later than the period of rapid uplift in the QTP. We also speculated that H. kamiyai differentiation was caused by host differentiation due to the favorable living conditions brought about by the uplift of the QTP. As there have been relatively few investigations on the mitochondrial genome of H. kamiyai, our study could provide factual support for further studies of H. kamiyai on the QTP. We also emphasized the importance of further studies of its hosts, Neodon fuscus and cats, which will be important for further understanding the life cycle of H. kamiyai.

T(r)icky Environments: Higher Prevalence of Tick-Borne Zoonotic Pathogens in Rodents from Natural Areas Compared with Urban Areas.

Background: Urban areas are unique ecosystems with stark differences in species abundance and composition compared with natural ecosystems. These differences can affect pathogen transmission dynamics, thereby altering zoonotic pathogen prevalence and diversity. In this study, we screened small mammals from natural and urban areas in the Netherlands for up to 19 zoonotic pathogens, including viruses, bacteria, and protozoan parasites. Materials and Methods: In total, 578 small mammals were captured, including wood mice (Apodemus sylvaticus), bank voles (Myodes glareolus), yellow-necked mice (Apodemus flavicollis), house mice (Mus musculus), common voles (Microtus arvalis), and greater white-toothed shrews (Crocidura russula). We detected a wide variety of zoonotic pathogens in small mammals from both urban and natural areas. For a subset of these pathogens, in wood mice and bank voles, we then tested whether pathogen prevalence and diversity were associated with habitat type (i.e., natural versus urban), degree of greenness, and various host characteristics. Results: The prevalence of tick-borne zoonotic pathogens (Borrelia spp. and Neoehrlichia mikurensis) was significantly higher in wood mice from natural areas. In contrast, the prevalence of Bartonella spp. was higher in wood mice from urban areas, but this difference was not statistically significant. Pathogen diversity was higher in bank voles from natural habitats and increased with body weight for both rodent species, although this relationship depended on sex for bank voles. In addition, we detected methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase/AmpC-producing Escherichia coli, and lymphocytic choriomeningitis virus for the first time in rodents in the Netherlands. Discussion: The differences between natural and urban areas are likely related to differences in the abundance and diversity of arthropod vectors and vertebrate community composition. With increasing environmental encroachment and changes in urban land use (e.g., urban greening), it is important to better understand transmission dynamics of zoonotic pathogens in urban environments to reduce potential disease risks for public health.

Re-wiring of the bonded brain: Gene expression among pair bonded female prairie voles changes as they transition to motherhood.

Motherhood is a costly life-history transition accompanied by behavioral and neural plasticity necessary for offspring care. Motherhood in the monogamous prairie vole is associated with decreased pair bond strength, suggesting a trade-off between parental investment and pair bond maintenance. Neural mechanisms governing pair bonds and maternal bonds overlap, creating possible competition between the two. We measured mRNA expression of genes encoding receptors for oxytocin (oxtr), dopamine (d1r and d2r), mu-opioids (oprm1a), and kappa-opioids (oprk1a) within three brain areas processing salience of sociosensory cues (anterior cingulate cortex; ACC), pair bonding (nucleus accumbens; NAc), and maternal care (medial preoptic area; MPOA). We compared gene expression differences between pair bonded prairie voles that were never pregnant, pregnant (~day 16 of pregnancy), and recent mothers (day 3 of lactation). We found greater gene expression in the NAc (oxtr, d2r, oprm1a, and oprk1a) and MPOA (oxtr, d1r, d2r, oprm1a, and oprk1a) following the transition to motherhood. Expression for all five genes in the ACC was greatest for females that had been bonded for longer. Gene expression within each region was highly correlated, indicating that oxytocin, dopamine, and opioids comprise a complimentary gene network for social signaling. ACC-NAc gene expression correlations indicated that being a mother (oxtr and d1r) or maintaining long-term pair bonds (oprm1a) relies on the coordination of different signaling systems within the same circuit. Our study suggests the maternal brain undergoes changes that prepare females to face the trade-off associated with increased emotional investment in offspring, while also maintaining a pair bond.