ABSTRACT
Oligodendrocyte progenitor cells (OPCs) differentiation into oligodendrocytes (OLs) and subsequent myelination are two closely coordinated yet differentially regulated steps for myelin formation and repair in the CNS. Previously thought as an inhibitory factor by activating Wnt/beta-catenin signaling, we and others have demonstrated that the Transcription factor 7-like 2 (TCF7l2) promotes OL differentiation independent of Wnt/beta-catenin signaling activation. However, it remains elusive if TCF7l2 directly controls CNS myelination separating from its role in upstream oligodendrocyte differentiation. This is partially because of the lack of genetic animal models that could tease out CNS myelination from upstream OL differentiation. Here, we report that constitutively depleting TCF7l2 transiently inhibited oligodendrocyte differentiation during early postnatal development, but it impaired CNS myelination in the long term in adult mice. Using time-conditional and developmental-stage-specific genetic approaches, we further showed that depleting TCF7l2 in already differentiated OLs did not impact myelin protein gene expression nor oligodendroglial populations, instead, it perturbed CNS myelination in the adult. Therefore, our data convincingly demonstrate the crucial role of TCF7l2 in regulating CNS myelination independent of its role in upstream oligodendrocyte differentiation.
ABSTRACT
Neuroinflammation, blood-brain barrier (BBB) dysfunction, neuron and glia injury/death and myelin damage are common central nervous system (CNS) pathologies observed in various neurological diseases and injuries. Serine protease inhibitor (Serpin) clade A member 3n (Serpina3n), and its human orthologue SERPINA3, is an acute-phase inflammatory glycoprotein secreted primarily by the liver into the bloodstream in response to systemic inflammation. Clinically, SERPINA3 is dysregulated in brain cells, cerebrospinal fluid and plasma in various neurological conditions. Although it has been widely accepted that Serpina3n/SERPINA3 is a reliable biomarker of reactive astrocytes in diseased CNS, recent data have challenged this well-cited concept, suggesting instead that oligodendrocytes and neurons are the primary sources of Serpina3n/SERPINA3. The debate continues regarding whether Serpina3n/SERPINA3 induction represents a pathogenic or a protective mechanism. Here, we propose possible interpretations for previously controversial data and present perspectives regarding the potential role of Serpina3n/SERPINA3 in CNS pathologies, including demyelinating disorders where oligodendrocytes are the primary targets. We hypothesise that the 'good' or 'bad' aspects of Serpina3n/SERPINA3 depend on its cellular sources, its subcellular distribution (or mis-localisation) and/or disease/injury types. Furthermore, circulating Serpina3n/SERPINA3 may cross the BBB to impact CNS pathologies. Cell-specific genetic tools are critically important to tease out the potential roles of cell type-dependent Serpina3n in CNS diseases/injuries.
Subject(s)
Serpins , Humans , Serpins/metabolism , Serpins/genetics , Animals , Central Nervous System Diseases/pathology , Central Nervous System Diseases/metabolism , Central Nervous System/pathology , Central Nervous System/metabolism , Blood-Brain Barrier/pathology , Blood-Brain Barrier/metabolismABSTRACT
BACKGROUND: Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. METHODS: An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. RESULTS: The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. CONCLUSIONS: Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.
ABSTRACT
Soil nitrogen (N) is an essential nutrient for tree growth, and excessive N is a source of pollution. This paper aims to define the effects of plant diversity and forest structure on various aspects of soil N cycling. Herein, we collected soils from 720 plots to measure total N content (TN), alkali-hydrolyzed N (AN), nitrate N (NO3--N), ammonium N (NH4+-N) in a 7.2 ha experimental forest in northeast China. Four plant diversity indices, seven structural metrics, four soil properties, and in situ N2O efflux were also measured. We found that: 1) high tree diversity had 1.3-1.4-fold NO3--N, 1.1-fold NH4+-N, and 1.5-1.8-fold N2O efflux (p < 0.05). 2) Tree growth decreased soil TN, AN, and NO3--N by more than 13%, and tree mixing and un-uniform distribution increased TN, AN, and NH4+-N by 11-22%. 3) Soil organic carbon (SOC) explained 34.3% of the N variations, followed by soil water content (1.5%), tree diameter (1.5%) and pH (1%), and soil bulk density (0.5%). SOC had the most robust linear relations to TN (R2 = 0.59) and AN (R2 = 0.5). 4) The partial least squares path model revealed that the tree diversity directly increased NO3--N, NH4+-N, and N2O efflux, and they were strengthened indirectly from soil properties by 1%-4%. The effects of tree size-density (-0.24) and spatial structure (0.16) were mainly achieved via their soil interaction and thus indirectly decreased NH4+-N, AN, and TN. Overall, high tree diversity forests improved soil N availability and N2O efflux, and un-uniform spatial tree assemblages could partially balance the soil N consumed by tree growth. Our data support soil N management in high northern hemisphere temperate forests from tree diversity and forest structural regulations.
Subject(s)
Soil , Trees , Soil/chemistry , Carbon , Forests , Nitrogen/analysis , ChinaABSTRACT
Since the Covid-19 pandemic, there has been an increasing growing need for learning experience or instructional designers. As a result, online courses on user experience (UX) design for learning are in demand to prepare those much-needed professionals. This paper reports the first circle of educational design research (EDR) on such a completely online problem-based course using group contracts and peer-evaluations to promote collaborations. Multiple datasets were collected from a range of data sources from a graduate-level course and were analyzed by two researchers. The study yielded several meaningful results: (1) group contracts helped students work smoothly and keep goals focused on collaborative learning in PBL; (2) the instructor could facilitate the group formation process; (3) peer evaluations helped group collaboration and monitoring; and (4) collaborative technologies are critical for collaboration. The findings also revealed important design principles for collaborative learning in PBL that can be used in similar courses. In addition, this study provides a successful example of how to teach UX design in an online PBL environment, and sheds light on how to further improve similar practices while contributing to the limited body of research on UX design for learning. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-022-11495-6.
ABSTRACT
The need for computer science (CS) education, especially computer network education, is increasing. However, the challenges of teaching students with diverse backgrounds and engaging them in hands-on activities to apply theories into practices exist in CS education. The study addressed the challenges by using project-based learning (PBL) and flipped teaching approaches to cover both theoretical and hands-on learning aspects in CS education. This study aims to demonstrate the design and development journey of a CS course and examine whether using PBL, hands-on activities, and flipped teaching approaches improves students' learning. The design-based research study was conducted in an undergraduate CS course from 2014 to 2020 at a midwestern university. The design and development trajectory in the six years were described. The descriptive statistics were used to analyze the trends of the course evaluation results, and ANOVA were conducted to examine whether the evaluation differs from each semester. The results indicated that using PBL, hands-on activities, and flipped teaching increased students' learning motivation and their perceptions of their learning. Combining PBL and flipped teaching appropriately can enhance students' learning motivation and perceived learning in CS education, but further research is needed to examine how each individual intervention influence students' learning motivation and learning outcomes.
ABSTRACT
Many universities in the U.S. shifted from in-person teaching to online teaching due to the COVID-19 pandemic. Instructors' acceptance of online teaching plays a crucial role, as the acceptance level can impact instructors' online teaching behaviors. This qualitative study examined medicine and public health instructors' perceptions of online teaching using the Technology Acceptance Model 2 (TAM2) model. Through semi-structured interviews with ten instructors in a Midwest university in the U.S., this study found that instructors had a high level of acceptance of online teaching. Instructors perceived the usefulness of online teaching in terms of learning objectives, assessment, instructional methods, and learning experience. Online teaching was perceived as useful overall, although challenges existed, such as online interaction, assessment, and hands-on practices. Regarding ease of use in online teaching, instructors perceived technology was easy to use; yet some pedagogical challenges existed, such as class engagement, the focus of learners' attention, and transforming hands-on lab or clinical sessions online. The blended model is recommended to use for teaching and learning in medical and public health education post the pandemic. Detailed implications for practice and research were discussed in the end.
ABSTRACT
Maladaptation to stress is a critical risk factor in stress-related disorders, such as major depression and post-traumatic stress disorder (PTSD). Dopamine signaling in the nucleus accumbens (NAc) has been shown to modulate behavior by reinforcing learning and evading aversive stimuli, which are important for the survival of animals under environmental challenges such as stress. However, the mechanisms through which dopaminergic transmission responds to stressful events and subsequently regulates its downstream neuronal activity during stress remain unknown. To investigate how dopamine signaling modulates stress-coping behavior, we measured the subsecond fluctuation of extracellular dopamine concentration and pH using fast scanning cyclic voltammetry (FSCV) in the NAc, a postsynaptic target of midbrain dopaminergic neurons, in male mice engaged in a tail suspension test (TST). The results revealed a transient decrease in dopamine concentration and an increase in pH levels when the animals changed behaviors, from being immobile to struggling. Interestingly, optogenetic inhibition of dopamine release in NAc, potentiated the struggling behavior in animals under the TST. We then addressed the causal relationship of such a dopaminergic transmission with behavioral alterations by knocking out both the dopamine receptors, i.e., D1 and D2, in the NAc using viral vector-mediated genome editing. Behavioral analyses revealed that male D1 knock-out mice showed significantly more struggling bouts and longer struggling durations during the TST, while male D2 knock-out mice did not. Our results therefore indicate that D1 dopaminergic signaling in the NAc plays a pivotal role in the modulation of stress-coping behaviors in animals under tail suspension stress.SIGNIFICANCE STATEMENT The tail suspension test (TST) has been widely used as a despair-based behavioral assessment to screen the antidepressant so long. Despite its prevalence in the animal studies, the neural substrate underlying the changes of behavior during the test remains unclear. This study provides an evidence for a role of dopaminergic transmission in the modulation of stress-coping behavior during the TST, a despair test widely used to screen the antidepressants in rodents. Taking into consideration the fact that the dopamine metabolism is upregulated by almost all antidepressants, a part of which acts directly on the dopaminergic transmission, current results would uncover the molecular mechanism through which the dopaminergic signaling mediates antidepressant effect with facilitation of the recovery from the despair-like behavior in the TST.
Subject(s)
Adaptation, Psychological , Dopamine/metabolism , Dopaminergic Neurons/metabolism , Nucleus Accumbens/metabolism , Stress, Psychological/metabolism , Animals , Cell Line, Tumor , Dopaminergic Neurons/physiology , Male , Mice , Mice, Inbred C57BL , Nucleus Accumbens/cytology , Nucleus Accumbens/physiopathology , Receptors, Dopamine/genetics , Receptors, Dopamine/metabolism , Stress, Psychological/physiopathology , Synaptic TransmissionABSTRACT
This case study explored effective instructional strategies and technology use in blended learning (BL) in a graduate course in the USA. Varied forms of data were collected, including (1) semi-structured interviews with students, (2) mid-term and final course evaluations, (3) two rounds of online debates, (4) four weeks of online reflection journals, and (5) the instructor's reflections. Thematical analysis and descriptive statistics were conducted to analyze qualitative and quantitative data respectively. Multiple methods were employed to establish trustworthiness of the study. Effective and ineffective instructional strategies and technology uses were identified in BL. The findings indicated that students valued real-time interactions with peers and the instructor. However, inappropriate asynchronous discussions were considered less effective in BL. In addition, immediate feedback from peers and the instructor motivated learners and improved the quality of their work. Learning technologies played a critical role in BL, but the use of learning technologies should be simplified and streamlined. Technical support was essential to reduce learners' cognitive load.
ABSTRACT
The habenula is an evolutionarily conserved structure in the vertebrate brain. Lesion and electrophysiological studies in animals have suggested that it is involved in the regulation of monoaminergic activity through projection to the brain stem nuclei. Since studies in animal models of depression and human functional imaging have indicated that increased activity of the habenula is associated with depressive phenotypes, this structure has attracted a surge of interest in neuroscience research. According to pathway- and cell-type-specific dissection of habenular function in animals, we have begun to understand how the heterogeneity of the habenula accounts for alteration of diverse physiological functions in depression. Indeed, recent studies have revealed that the subnuclei embedded in the habenula show a wide variety of molecular profiles not only in neurons but also in glial cells implementing the multifaceted regulatory mechanism for output from the habenula. In this review, we overview the known facts on mediolateral subdivision in the habenular structure, then discuss heterogeneity of the habenular structure from the anatomical and functional viewpoint to understand its emerging role in diverse neural functions relevant to depressive phenotypes. Despite the prevalent use of antidepressants acting on monoamine metabolisms, ~30% of patients with major depression are reported to be treatment-resistant. Thus, cellular mechanisms deciphering such diversity in depressive symptoms would be a promising candidate for the development of new antidepressants.
Subject(s)
Anhedonia/physiology , Depressive Disorder, Major/physiopathology , Habenula/anatomy & histology , Habenula/physiopathology , Animals , HumansABSTRACT
The first anti-stereoselective asymmetric ring-opening reactions of azabenzonorbornadienes with carboxylic acids have been realized with an iridium catalyst assisted by nBu4NBr. The reaction features broad substrate scope and good functional group tolerance and allows the synthesis of chiral dihydronaphthalene derivatives with high optical purities.
ABSTRACT
Serine protease inhibitor clade A member 3n (Serpina3n) or its human orthologue SERPINA3 is a secretory glycoprotein expressed primarily in the liver and brain under homeostatic conditions and dysregulated in various CNS pathologies. Yet its cellular expression profile and physiological significance in postnatal development remain elusive. Here, we showed that Serpina3n protein is expressed predominantly in oligodendroglial lineage cells in the postnatal CNS and that oligodendrocytes (OLs) responded to oxidative injury by upregulating Serpina3n production and secretion. Using loss-of-function genetic tools, we found that Serpina3n conditional knockout (cKO) from Olig2-expressing cells did not affect motor and cognitive functions in mice. Serpina3n depletion in Olig2-expressing cells did not appear to interfere with oligodendrocyte differentiation and developmental myelination nor affect the population of other glial cells and neurons in vivo. In vitro primary cell culture showed that Serpina3n-sufficient and -deficient oligodendroglial progenitor cells (OPCs) differentiated into myelin gene-expressing OLs comparatively. Together, these data suggest that Serpina3n plays a minor role, if any, in regulating brain neural cell development and myelination under homeostatic conditions and raise interests in pursuing its functional significance in CNS diseases and injuries.
ABSTRACT
Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N-acetyl-l-aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium-coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase-deficient Canavan disease model mice ("CD mice") reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.
Subject(s)
Canavan Disease , Neurodegenerative Diseases , Animals , Mice , Aspartic Acid , Astrocytes , Brain , Canavan Disease/genetics , Canavan Disease/therapy , OligodendrogliaABSTRACT
Appropriate proliferation and repopulation of oligodendrocyte progenitor cells (OPCs) determine successful (re)myelination in homeostatic and demyelinating brains. Activating mutations in p21-activated kinase 1 (PAK1) cause intellectual disability, neurodevelopmental abnormality, and white matter anomaly in children. It remains unclear if and how PAK1 regulates oligodendroglial development. Here, we report that PAK1 controls proliferation and regeneration of OPCs. Unlike differentiating oligodendrocytes, OPCs display high PAK1 activity which maintains them in a proliferative state by modulating PDGFRa-mediated mitogenic signaling. PAK1-deficient or kinase-inhibited OPCs reduce their proliferation capacity and population expansion. Mice carrying OPC-specific PAK1 deletion or kinase inhibition are populated with fewer OPCs in the homeostatic and demyelinated CNS than control mice. Together, our findings suggest that kinase-activating PAK1 mutations stall OPCs in a progenitor state, impacting timely oligodendroglial differentiation in the CNS of affected children and that PAK1 is a potential molecular target for replenishing OPCs in demyelinating lesions.
ABSTRACT
In this paper, the effects of species diversity, tree growth, and spatial clustering on mycorrhizal carbon and nitrogen sequestration and the interaction of soil physicochemical properties in Northeast China were investigated. Based on 720 10 m ∗ 10 m plots in Harbin Experimental Forest Farm of Northeast Forestry University, we determined mycorrhizal biomarkers of easily extractable Glomalin-related soil protein (EEG) and total Glomalin-related soil protein (TG). Four plant diversity indices, seven structural metrics, and five soil properties were also measured. We found that: 1) The low tree diversity plots had 1.08-1.23 times higher TG, EEG, TG-N/TN (proportion of N in TG to TN), and TG-C/SOC (proportion of C in TG to SOC) than the high plots. 2) Tree diameter was negatively correlated with EEG and TG, but positively correlated with the EEG and TG contribution to soil TN and SOC. Soil EEG and TG were positively correlated with under-branch height and tree density. W (Uniform Angle Index, higher W indicates more clustering of tree distribution in the plot) was negatively correlated with the above four ratios and positively correlated with EEG/TG. 3) pH was the most powerful explainer for the GRSP variations (6.8 %, strongest negative association with GRSP/TN, R2 > 0.13), followed by soil electrical conductance (6.5 %, positive relation with TG, p < 0.05), AP (3.2 %). 4) Plant diversity mainly affected GRSP traits through the interaction with soils (0.07), tree growth and density directly increased TG, TG-N/TN, and TG-C/SOC, while tree spatial distribution directly reduced TG-N/TN. Our finding highlighted the important effects of tree diversity and forest structural traits on GRSP amount, carbon sequestration, and nutrient retentions, and could support glomalin-related forest soil management of temperate forests in the high-latitude northern hemisphere.
Subject(s)
Mycorrhizae , Soil , Humans , Soil/chemistry , Trees/metabolism , Mycorrhizae/metabolism , Forests , Fungal Proteins/metabolism , Glycoproteins/metabolism , China , Carbon/analysisABSTRACT
ABSTRACT: Significant numbers of patients who survive sepsis exhibit psychiatric and cognitive impairments, termed post-sepsis syndrome. Understanding the underlying pathophysiology is essential to develop effective therapies. Translocator protein 18 kDa (TSPO) is a multifaceted mitochondrial protein implicated in inflammation, oxidative stress, and steroidogenesis in the central nervous system. Despite accumulated evidence demonstrating TSPO is a biomarker in psychiatric and neurodegenerative disorders, the role of this protein in post-sepsis syndrome remains elusive. The aim of this study was to investigate the role of TSPO in the long-term impairment of mouse behavior associated with psychiatric and cognitive impairments following sepsis induced by cecal ligation and puncture (CLP) surgery. Animals were divided into three groups: (i) wild type (WT) + sham, (ii) WT + CLP, and (iii) TSPO knock out + CLP. Survival rate and body weight change were assessed up to 17 days after surgeries. Then, we also assessed anxiety-like behavior, depression-like behavior, cognitive function, locomotor activity, and forelimb muscle strength in surviving mice by elevated plus maze, tail suspension test, y-maze, open field test, and grip strength test, respectively. Deletion of the TSPO gene led to high mortality and prolonged weight loss and exacerbated anxiety-like and depressive-like behavior with cognitive impairment 17 days after, but not before, CLP surgery. RNA-seq analysis of the hippocampus revealed the upregulation of genes (C1qb, C1qc, and Tyrobp) in C1q complement pathways correlated significantly with anxiety-like behavior that appeared long after CLP surgery. The expressions of these genes predicted other behavioral traits, including depressive-like behavior in the tail suspension test and grip power impairment, supporting the role of the C1q pathway in post-sepsis syndrome. Because the C1q pathway has recently attracted interest as a tag for pathological synaptic elimination, the current study suggests the C1q pathway is involved in the psychiatric and cognitive impairments observed in post-sepsis syndrome.
Subject(s)
Cognitive Dysfunction , Complement C1q , Receptors, GABA , Sepsis , Animals , Anxiety/genetics , Cognitive Dysfunction/genetics , Inflammation/etiology , Sepsis/complications , Sepsis/genetics , Sepsis/metabolism , Mice , Receptors, GABA/geneticsABSTRACT
High water-holding forests are essential for adapting to drought climates under global warming, and a central issue is which type of forests could conserve more water in the ecosystem. This paper explores how forest structure, plant diversity, and soil physics impact forest water-holding capacities. We investigated 720 sampling plots by measuring water-holding capacities from 1440 soil and litter samples, 8400 leaves, and 1680 branches and surveying 18,054 trees in total (28 species). Water-holding capacities were measured as four soil indices (Maxwc, maximum water-holding capacity; Fcwc, field water-holding capacity; Cpwc, soil capillary water-holding capacity; Ncpwc, non-capillary water-holding capacity), two litter metrics (Maxwcl, maximum water-holding capacity of litters; Ewcl, effective water-holding capacity of litters), and canopy interception (C, the sum of estimated water interception of all branches and leaves of all tree species in the plot). We found that water-holding capacity in the big-sized tree plots was 4-25 % higher in the litters, 54-64 % in the canopy, and 6-37 % in the soils than in the small-sized plots. The higher species richness increased all soil water-holding capacities compared to the lowest richness plot. Higher Simpson and Shannon-Wiener plots had 10-27 % higher Ewcl and C than the lowest plots. Bulk density had the strongest negative relations with Maxwc, Cpwc, and Fcwc, whereas field soil water content positively affected them. Soil physics, forest structure, and plant diversity explained 90.5 %, 5.9 %, and 0.2 % of the water-holding variation, respectively. Tree sizes increased C, Ncpwc, Ewcl directly (p < 0.05), and richness increased Ewcl directly (p < 0.05). However, the direct effects from the uniform angle index (tree distribution evenness) were balanced by their indirect effect from soil physics. Our findings highlighted that the mixed forests with big-sized trees and rich species could effectively improve the water-holding capacities of the ecosystem.
Subject(s)
Ecosystem , Trees , Water , Biodiversity , Forests , China , Soil/chemistryABSTRACT
In massive open online learning courses (MOOCs) with a low instructor-student ratio, students are expected to have self-directed learning abilities. This study investigated the relationship among motivation, self-monitoring, self-management, and MOOC learners' use of learning strategies. An online survey was embedded at the end of three MOOCs with large enrollments asking for learners' voluntary participation in the study. The survey results from 470 participants indicated that motivation positively influenced self-monitoring, self-management, and learning strategies. In addition, self-monitoring and self-management did not affect the utilization of learning strategies. This underscores learners' motivation and the need to encourage them to adopt appropriate learning strategies for successful learning. The results also revealed that self-monitoring positively affected self-management. The findings highlight the critical need to enhance self-monitoring skills to further promote self-management skills in MOOCs. In addition, self-monitoring and self-management did not encourage learners to use related learning strategies in this study. This study should be extended to investigate practical ways to encourage MOOC learners to adopt learning strategies.
ABSTRACT
Children with SOX2 deficiency develop ocular disorders and extra-ocular CNS anomalies. Animal data show that SOX2 is essential for retinal and neural stem cell development. In the CNS parenchyma, SOX2 is primarily expressed in astroglial and oligodendroglial cells. Here, we report a crucial role of astroglial SOX2 in postnatal brain development. Astroglial Sox2-deficient mice develop hyperactivity in locomotion and increased neuronal excitability in the corticostriatal circuit. Sox2 deficiency inhibits postnatal astrocyte maturation molecularly, morphologically, and electrophysiologically without affecting astroglia proliferation. Mechanistically, SOX2 directly binds to a cohort of astrocytic signature and functional genes, the expression of which is significantly reduced in Sox2-deficient CNS and astrocytes. Consistently, Sox2 deficiency remarkably reduces glutamate transporter expression and compromised astrocyte function of glutamate uptake. Our study provides insights into the cellular mechanisms underlying brain defects in children with SOX2 mutations and suggests a link of astrocyte SOX2 with extra-ocular abnormalities in SOX2-mutant subjects.
Subject(s)
Astrocytes , Neural Stem Cells , Mice , Animals , Astrocytes/metabolism , Brain , Neurons/metabolism , Cell DifferentiationABSTRACT
Voluntary wheel-running activity is a way to assess rodents' circadian rhythm and motivation for exercise. Deficits in these behaviors are implicated in the pathophysiology of sleep and psychiatric disorders. Limited space in animal facilities can hamper long-term monitoring of running wheel activity outside of the home cage. To address this issue, we provide a stand-alone solution to monitor the wheel-running activity of mice in their home cage. This system, named the wheel-running activity acquisition (WRAQ) system, is based on a microcontroller driven by a lithium polymer battery. With the WRAQ, we can record the wheel-running activity and illumination data for at least 30 d. Applying the WRAQ to an endotoxemia mouse model robustly detected the altered wheel-running activity and its recovery. With wireless data transfer capability extension, the system also allows for online monitoring and reporting of the circadian time (CT). We used the online monitoring of wheel-running activity with this extended WRAQ system and observed a significant shift of the active period in the circadian rhythm following a temporal chemogenetic activation of the suprachiasmatic nucleus (SCN)-subparaventricular zone (SPZ). Together, these findings indicate that the WRAQ system is a novel and cost-effective solution for the analysis of wheel-running activity in mice.