Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study.

OBJECTIVES: To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA. METHODS: In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI). RESULTS: In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA. After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis. CONCLUSIONS: We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.

A new serum biochemical marker of synovium turnover predicts radiographic progression in patients with early arthritis.

OBJECTIVE: To investigate whether serum Col 3-4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis. METHODS: A total of 788 early arthritis patients (<6 months of symptoms, 82% diagnosis of RA, 18% undifferentiated arthritis) from the prospective ESPOIR study were investigated. Progression was defined as an increase of 1 or 5 unit(s) in radiographic van der Heijde modified Sharp score between baseline and 1 or 5 years, respectively. Associations between baseline Col 3-4 and progression were assessed by logistic regression. RESULTS: Each standard deviation increase of baseline Col 3-4 levels was associated with an increased 5-yr total damage progression with an odds ratio (OR, 95% CI) of 1.51 (1.21, 1.88), which remained significant when DAS28, C-reactive protein and anti-citrullinated protein antibodies positivity were included in the model [OR (95% CI): 1.34 (1.01, 1.76)]. Further adjustment for bone erosion did not modify the association. Patients with both Col 3-4 in the highest quintile and bone erosion had a >2-fold higher risk of progression [OR (95% CI): 7.16 (2.31, 22)] than patients with either high Col 3-4 [2.91 (1.79, 4.73)] or bone erosion [2.36 (2.38, 3.70)] alone. Similar associations were observed for prediction of 12 months progression. CONCLUSIONS: Increased serum Col 3-4 is associated with a higher risk of structural progression, independently of major risk factors. Col 3-4 may be useful in association with bone erosion to identify patients with early arthritis at higher risk.

Plasma Cartilage Acidic Protein 1 Measured by ELISA Is Associated With the Progression to Total Joint Replacement in Postmenopausal Women.

OBJECTIVE: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women. METHODS: The association of plasma CRTAC1 with the incidence of TJR was investigated in a prospective cohort including 478 postmenopausal women. A total of 38 women underwent a TJR for OA during a median follow-up of 18 years. Every one of the TJR cases were age- and BMI (kg/m2)-matched with 2 controls with no TJR from the same cohort. Plasma CRTAC1 was measured before TJR. The association between CRTAC1 and TJR incidence was investigated by conditional logistic regression. RESULTS: Increased CRTAC1 was associated with a higher risk of TJR with an odds ratio (OR) of 1.80 (95% CI 1.11-2.92) for 1 SD increase, which remained significant after adjusting for Western Ontario and McMaster Universities Osteoarthritis Index, knee OA baseline severity (Kellgren-Lawrence grade), hip OA, and hip bone mineral density. Urinary crosslinked C-telopeptide of type II collagen (CTX-II) was also associated with a higher risk of TJR with an adjusted OR of 1.83 (95% CI 1.11-3.00). When CRTAC1 and CTX-II were included in the same model, both markers were significantly associated with TJR with similar ORs. CONCLUSION: CRTAC1 is a new risk indicator of TJR for OA in postmenopausal women. Combined with knee and hip OA and CTX-II, it may help to identify subjects at risk for TJR.

Association of circulating hsa-miRNAs with sarcopenia: the SarcoPhAge study.

OBJECTIVE: To identify a microRNA signature associated to sarcopenia in community-dwelling older adults form the SarcoPhAge cohort. METHODS: In a screening phase by next generation sequencing (NGS), we compared the hsa-miRome expression of 18 subjects with sarcopenia (79.6 ± 6.8 years, 9 men) and 19 healthy subjects without sarcopenia (77.1 ± 6 years, 9 men) at baseline. Thereafter, we have selected eight candidate hsa-miRNAs according to the NGS results and after a critical assessment of previous literature. In a validation phase and by real-time qPCR, we then analyzed the expression levels of these 8 hsa-miRNAs at baseline selecting 92 healthy subjects (74.2 ± 10 years) and 92 subjects with sarcopenia (75.3 ± 6.8 years). For both steps, the groups were matched for age and sex. RESULTS: In the validation phase, serum has-miRNA-133a-3p and has-miRNA-200a-3p were significantly decreased in the group with sarcopenia vs controls [RQ: relative quantification; median (interquartile range)]: -0.16 (-1.26/+0.90) vs +0.34 (-0.73/+1.33) (p < 0.01) and -0.26 (-1.07/+0.68) vs +0.27 (-0.55/+1.10) (p < 0.01) respectively. Has-miRNA-744-5p was decreased and has-miRNA-151a-3p was increased in the group with sarcopenia vs controls, but this barely reached significance: +0.16 (-1.34/+0.79) vs +0.44 (-0.31/+1.00) (p = 0.050) and +0.35 (-0.22/+0.90) vs +0.03 (-0.68/+0.75) (p = 0.054). CONCLUSION: In subjects with sarcopenia, serum hsa-miRNA-133a-3p and hsa-miRNA-200a-3p expression were downregulated, consistent with their potential targets inhibiting muscle cells proliferation and differentiation.

Le rôle des pairs chercheurs dans la recherche sur la consommation sexualisée de substances : avantages et défis.

CONTEXT: Sexual and gender diverse individuals (SGDI) report higher usage of methamphetamine in sexual contexts. They face difficulties making sense of their experiences and being heard in services. Peer researchers (individuals with lived experience) were involved in a participatory study on methamphetamine consumption. OBJECTIVES: 1) To describe the opportunities and challenges of involving peer researchers in all stages of the research process; 2) To discuss how this involvement could address the epistemic injustice experienced by SGDI who practice chemsex. METHODOLOGY: The peer-researcher participatory process was documented through a journal and meeting notes, which were analyzed through the framework of epistemic injustice. This notion refers to the mechanisms that prevent the knowledge of a person or group from being heard and considered legitimate. RESULTS: The contribution of peer researchers was highly valued and raised questions. Their in-depth knowledge facilitated data analysis and guided knowledge dissemination, promoting the transformation of current services. Their presence also helped to establish relationships of trust with the study population. DISCUSSION: This connection with the study population can create expectations for services that may require a significant level of involvement from researchers. The team’s commitment to improving services can generate a mistaken perception of a lack of objectivity.

The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis.

Periostin is an extracellular matrix protein that actively contributes to tumor progression and metastasis. Here, we hypothesized that it could be a marker of bone metastasis formation. To address this question, we used two polyclonal antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of periostin in the serum and tissues (lung, heart, bone) of wild-type and periostin-deficient mice. In normal bones, periostin was expressed in the periosteum and specific periostin proteolytic fragments were found in bones, but not in soft tissues. In animals bearing osteolytic lesions caused by 4T1 cells, C-terminal intact periostin (iPTN) expression disappeared at the invasive front of skeletal tumors where bone-resorbing osteoclasts were present. In vitro, we found that periostin was a substrate for osteoclast-derived cathepsin K, generating proteolytic fragments that were not recognized by anti-periostin antibodies directed against iPTN. In vivo, using an in-house sandwich immunoassay aimed at detecting iPTN only, we observed a noticeable reduction of serum periostin levels (- 26%; P < 0.002) in animals bearing osteolytic lesions caused by 4T1 cells. On the contrary, this decrease was not observed in women with breast cancer and bone metastases when periostin was measured with a human assay detecting total periostin. Collectively, these data showed that mouse periostin was degraded at the bone metastatic sites, potentially by cathepsin K, and that the specific measurement of iPTN in serum should assist in detecting bone metastasis formation in breast cancer.

Respiratory consequences of targeted losses of Hoxa5 gene function in mice.

Fetal development of the respiratory tract and diaphragm requires strict coordination between genetically controlled signals and mechanical forces produced by the neural network that generates breathing. HOXA5, which is expressed in the mesenchyme of the trachea, lung and diaphragm, and in phrenic motor neurons, is a key transcription factor regulating lung development and function. Consequently, most Hoxa5-/- mutants die at birth from respiratory failure. However, the extensive effect of the null mutation makes it difficult to identify the origins of respiratory dysfunction in newborns. To address the physiological impact of Hoxa5 tissue-specific roles, we used conditional gene targeting with the Dermo1Cre and Olig2Cre mouse lines to produce specific Hoxa5 deletions in the mesenchyme and motor neurons, respectively. Hoxa5 expression in the mesenchyme is critical for trachea development, whereas its expression in phrenic motor neurons is essential for diaphragm formation. Breathing measurements in adult mice with whole-body plethysmography demonstrated that, at rest, only the motor neuron deletion affects respiration, resulting in higher breathing frequency and decreased tidal volume. But subsequent exposure to a moderate hypoxic challenge (FiO2 =0.12; 10 min) revealed that both mutant mice hyperventilate more than controls. Hoxa5flox/flox;Dermo1+/Cre mice showed augmented tidal volume while Hoxa5flox/flox;Olig2+/Cre mice had the largest increase in breathing frequency. No significant differences were observed between medulla-spinal cord preparations from E18.5 control and Hoxa5flox/flox;Olig2+/Cre mouse embryos that could support a role for Hoxa5 in fetal inspiratory motor command. According to our data, Hoxa5 expression in the mesenchyme and phrenic motor neurons controls distinct aspects of respiratory development.

Spectral-phase interferometry for direct electric-field reconstruction applied to seeded extreme-ultraviolet free-electron lasers.

We present a setup for complete characterization of femtosecond pulses generated by seeded free-electron lasers (FELs) in the extreme-ultraviolet spectral region. Two delayed and spectrally shifted replicas are produced and used for spectral phase interferometry for direct electric field reconstruction (SPIDER). We show that it can be achieved by a simple arrangement of the seed laser. Temporal shape and phase obtained in FEL simulations are well retrieved by SPIDER reconstructions, allowing to foresee the implementation of this diagnostics tool on existing and future sources. This will be a significant step towards an experimental investigation and control of FEL spectral phase.

Carrier-envelope-phase stable, high-contrast, double chirped-pulse-amplification laser system.

We present the first carrier-envelope-phase stable chirped-pulse amplifier (CPA) featuring high temporal contrast for relativistic intensity laser-plasma interactions at 1 kHz repetition rate. The laser is based on a double-CPA architecture including cross-polarized wave (XPW) filtering technique and a high-energy grism-based compressor. The 8 mJ, 22 fs pulses feature 10⁻¹¹ temporal contrast at -20 ps and a carrier-envelope-phase drift of 240 mrad root mean square.

Periostin and transforming growth factor ß-induced protein (TGFßIp) are both expressed by osteoblasts and osteoclasts.

Periostin (Postn) and transforming growth factor ß-induced protein (TGFßIp) are two closely related extracellular matrix (ECM) proteins predominantly distributed in collagen-rich connective tissues submitted to mechanical strain, including bone and more specifically the periosteum. We have investigated the expression of Postn and TGFßIp mRNA by primary osteoblasts isolated from mouse periosteum and calvaria, or by the osteoblast-like MC3T3-E1 cell line, and by osteoclasts from mouse long bones differentiated in vitro. Secretion of Postn was measured with a specific ELISA. Postn and TGFßIp mRNA were concomitantly expressed in all three osteoblast models all along the differentiation process in a time-dependent manner. Both Postn and TGFßIp transcripts appeared early in osteoblast differentiation, and their expression increased 3-10 times in mature osteoblast cells. Expression decreased after differentiation was achieved and when the cultures mineralised. ELISA for secreted Postn showed a similar pattern. When MC3T3-E1 cells were treated with TGF-ß, Postn and TGFßIp mRNA expression and secretion were stimulated, whereas 1.25(OH)(2)D(3) had no detectable effect. Osteoclasts also expressed both Postn and TGFßIp during in vitro differentiation. Expression of both Postn and TGFßIp peaks in the early phases of osteoblast differentiation, and decreases later at the start of mineralisation. A novel finding is that Postn and TGFßIp are expressed by osteoclasts in vitro. Therefore Postn and TGFßIp proteins are potential biomarkers of early osteoblast differentiation and new bone formation.

Cardiac arrest: should we consider norepinephrine instead of epinephrine?

A patient scheduled for a laparoscopic cholecystectomy had an anaphylactic shock during induction of anesthesia. After the injection of vecuronium, an unusual fall of arterial pressure occurred, with bradycardia, enlargement of the QRS complex, then a circulatory arrest. Chest compressions were initiated, while intravenous epinephrine 1 mg was administered. The cardiac rhythm turned into a ventricular fibrillation (VF). Despite continuous chest compressions with repeated boluses of epinephrine and several external electric shocks, the patient remained in VF. Because of obviously ß-adrenergic adverse effects, epinephrine was replaced with norepinephrine. Return of spontaneous circulation was observed, with the recovering of sinusal activity. After staying for several weeks in intensive care unit because of multiorgan failure, the patient recovered without sequelae. Blood samples and cutaneous testing confirmed an allergy to vecuronium. This case report of a cardiac anaphylaxis with prolonged cardiac arrest illustrates the dual activity and adverse effects of epinephrine. Although vasoconstriction is mandated during cardiopulmonary resuscitation to provide an acceptable perfusion pressure to organs, ß-adrenergic stimulation seems deleterious to the heart. Experimental studies have shown that blocking the ß-adrenergic effects of epinephrine attenuates postresuscitation myocardial dysfunction or helps the return of spontaneous circulation after VF. Norepinephrine, a potent α-adrenergic drug nearly devoid of ß-adrenergic properties, could be an interesting alternative to epinephrine. It can improve organ perfusion during cardiopulmonary resuscitation and could be more efficient than epinephrine in case of VF.

On thermal characterization method of integrated magnetic components.

The operating temperature of integrated magnetic components can be critical. Excessively high temperature can significantly modify the properties of components, especially those of magnetic material, such as saturation magnetization and magnetic permeability. This article introduces an experimental characterization method using two different sensors. We compare the results obtained from these sensors. Initially, the method is validated using a "meander component, and subsequently, it is applied to planar spiral inductors, both with and without magnetic material.

Medullary tachykinin precursor 1 neurons promote rhythmic breathing.

Rhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 or Tac1). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impair rhythmic breathing. Although, the application of substance P to the preBötC stimulates breathing in rodents, substance P is also involved in nociception and locomotion in various brain regions, suggesting that Tac1 neurons found in the preBötC may have diverse functional roles. Here, we characterized the role of Tac1-expressing preBötC neurons in the generation of rhythmic breathing in vivo, as well as motor behaviors. Using a cre-lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region of Tac1-cre mice. Employing a combination of histological, optogenetics, respiratory, and behavioral assays, we showed that stimulation of glutamatergic or Tac1 preBötC neurons promoted rhythmic breathing in both anesthetized and freely moving animals, but also triggered locomotion and overcame respiratory depression by opioid drugs. Overall, our study identified a population of excitatory preBötC with major roles in rhythmic breathing and behaviors.

Serum Col3-4: A new type III and IV collagen biochemical marker of synovial tissue turnover in patients with rheumatoid arthritis.

The objective of this study was to develop a serum biochemical marker of the degradation of type III and IV collagens, as an index of synovium turnover, and evaluate its performance in patients with rheumatoid arthritis (RA). An enzyme-linked immunosorbent assay for serum synovial collagen fragments (Col3-4) was developed using an antibody recognizing a specific sequence from human type III collagen, which shares 70% homology with type IV collagen. Immunohistochemistry was performed to localize Col3-4 and the matrix metalloprotease MMP-9 which is upregulated in RA synovial fibroblasts in the synovial tissue from a RA patient. Serum Col3-4 was measured in patients with RA (n = 66, 73% women, mean age 62 years, median disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) 2.6) and in sex and age matched healthy controls (n = 70, 76% women, mean age 59 years). Col3-4 immunoassay demonstrated adequate analytical performances and recognized a circulating neoepitope resulting from the cleavage of type III and IV collagens. In RA synovium tissue, Col3-4 fragments were localized in the lining layer where destructive fibroblasts are present and around blood vessels rich in type IV collagen. MMP-9 colocalized with Col3-4 staining and efficiently released Col3-4 fragments from type III and type IV collagen digestion. Serum Col3-4 was markedly increased in patients with RA (+240% vs controls, p < 0.0001) and correlated with DAS28-ESR (r = 0.53, p < 0.0001). Patients with RA and active disease (DAS28-ESR > 3.2, n = 20) had 896% (p < 0.0001) higher levels than subjects with low activity (n = 46). Serum Col3-4 is a specific and sensitive biochemical marker reflecting MMP- mediated type III and IV collagen degradation from synovial tissue. Serum Col3-4 levels are markedly increased in patients with RA, particularly in those with active disease, suggesting that it may be useful for the clinical investigation of RA.

Field dataset of punctual observations of soil properties and vegetation types distributed along soil moisture gradients in France.

The interface between wetlands and uplands is characterized by gradients in hydrological, soil and biological components. Consequently, the exact spatial distribution of this transitional area is not well known because it often occurs as a fuzzy moisture gradient. However, ecological assessment and conservation require mapping and characterizing this interface to better understand and model biotic and abiotic interactions between wetlands and uplands. To this end, in 2021 and 2022, we observed soil properties and vegetation types along soil moisture gradients throughout the Atlantic, Continental, Mediterranean and Alpine biogeographic regions of France. The dataset contains 2 236 georeferenced plots (accuracy ± 5 m) distributed along 1 088 transects placed along the slope at 377 sites. Each plot in the database is characterized by 21 fields that describe the vegetation habitat type based on the European Nature Information System (EUNIS) and soil properties (i.e. depth of appearance and thickness of redoximorphic features in the soil profile, moisture). These data are useful for researchers and engineers in a variety of disciplines (e.g. Earth and life sciences) to calibrate and validate models to predict the spatial distribution of habitats or to analyze flows.

A case of combat-related scorpion envenomation in Afghanistan.

We report a case of scorpion envenomation occurring during combat in Tagab district, province of Kapisa, Afghanistan. A French soldier was stung by a yellow scorpion (suspected Androctonus australis) and sustained systemic envenomation with hemodynamic and neurological manifestations. We discuss the clinical features, prevention, and management of a scorpion sting.

Soluble biological markers in osteoarthritis.

In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.

Thyroid hormones during the perinatal period are necessary to respiratory network development of newborn rats.

Thyroid hormones (THs) are essential for foetal brain development. Because the gestating mother is the main source of THs to the foetus, maternal hypothyroidism and/or premature birth compromise neurological outcomes in the offspring. Respiratory instability and recurrent apneas due to immaturity of the respiratory control network are major causes of morbidity in infants. Inadequate TH supply may be sufficient to delay perinatal maturation of the respiratory control system; however, this hypothesis remains untested. To address this issue, maternal hypothyroidism was induced by adding methimazole (MMI; 0.02% w/v) to the drinking water of pregnant dams from conception to postpartum day 4 (P4). The effect of TH supplementation on respiratory function was tested by injecting levothyroxine (L-T4) in newborns at P1. Respiratory function was assessed by plethysmography (in vivo) and recording of phrenic output from medullary preparations (in vitro). By comparison with controls, TH deficiency increased the frequency of apneas and decreased basal ventilation in vivo and prevented the age-dependent increase in phrenic burst frequency normally observed in vitro. The effects of TH deficiency on GABAergic modulation of respiratory activity were measured by bath application of muscimol (GABAA agonist) or bicuculline (GABAA antagonist). The phrenic burst frequency responses to GABAergic agents were consistently greater in preparations from TH deficient pups. L-T4 supplementation reversed part of the respiratory anomalies related to MMI treatment in vitro. We conclude that TH deficiency during the perinatal period is sufficient to delay maturation of the respiratory control network development. Excessive GABAergic inhibition may contribute to this effect.

Inherent privacy limitations of decentralized contact tracing apps.

Recently, there have been many efforts to use mobile apps as an aid in contact tracing to control the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (COVID-19 [coronavirus disease 2019]) pandemic. However, although many apps aim to protect individual privacy, the very nature of contact tracing must reveal some otherwise protected personal information. Digital contact tracing has endemic privacy risks that cannot be removed by technological means, and which may require legal or economic solutions. In this brief communication, we discuss a few of these inherent privacy limitations of any decentralized automatic contact tracing system.

Facilitation of microglial motility by thyroid hormones requires the presence of neurons in cell culture: A distinctive feature of the brainstem versus the cortex.

Microglia are critical for the refinement of neural networks that takes place during the perinatal period. Their phenotype and actions are guided by the signals produced by neighbouring cells and hormones present in their surrounding milieu. Cell populations and the signals they produce differ between regions. The fact that thyroid hormones (THs) promote the growth and morphological differentiation of microglia within the cortex contributes to the TH's powerful actions on the developing brain. The brainstem is especially active during early life owing to its role in generation of the rhythmic respiratory motor command. Despite evidences indicating that THs are necessary to proper development of the neural networks regulating this vital homeostatic function, their actions on microglia originating from the brainstem remain unknown. Using primary cultured microglia from newborn mice (C57BL/6J), we first report that regulation of microglial motility by THs is different between cortex and brainstem. Microglial motility (µm traveled over 3 h) was monitored with or without triiodothyronine (T3, 1µM). Exposure to T3 did not stimulate microglial motility from brainstem, but significantly stimulated (316 %) when they were co-cultured with neurons. Motility of cortex microglia was stimulated to the similar extent either with or without neurons. These data suggest that the microglial function in different regions of the brain is determined by the surrounding environment.