Factors influencing nearshore hypoxia in the southeastern Arabian Sea: A sensor-based study.

Seasonal upwelling and the associated incursion of hypoxic waters into the coastal zone is a widely studied topic over different upwelling zones. However, its persistence or variations over short time scales are poorly addressed. The present study, therefore, brings out a first report on hourly variations in the temperature, salinity and dissolved oxygen recorded by an environmental data buoy equipped with sensors, deployed in the nearshore waters of Alappuzha (southeastern Arabian Sea) from April to August 2022. The characteristic feature of the Alappuzha coast is the development of mud banks during the southwest monsoon, providing a tranquil environment suitable for continuous sensor-based measurements when the sea remains turbulent elsewhere. The results showed that despite an advance in the upwelling intensity, there is a significant variation in the oxygen concentration in the study domain on a diurnal scale. In general, the nearshore region was under hypoxia during the first half of the day (00:00 to 12:00 h), which increased steadily to reach normoxic and supersaturated levels during the rest of the day (12:00 to 24:00 h). Statistical analysis showed that winds significantly correlate to the coastal environment's subsurface oxygen concentration. During the morning hours, the wind was weak, and the water column remained stratified over the subsurface hypoxic water layer. The situation changed in the afternoon (12:00 h onwards), as there was a steady increase in the local wind speed (>5 m/s), which was sustained during the rest of the day. A local wind speed >5 m/s can disturb the stratification and enhance the mixing process from 12:00 to 24:00 h. The total kinetic energy of 11.5 J/m3 is the threshold for this oxygen supersaturation. These findings emphasize the role of wind-induced mixing in alleviating coastal hypoxia, highlighting the need for further biogeochemical and ecological investigations into the impacts of alternating oxic-hypoxic conditions in nearshore waters.

Simple methods for cerebrospinal fluid collection in fetal, neonatal, and adult rat.

BACKGROUND: Cerebrospinal fluid (CSF) collection and its analysis are common medical practices useful in the diagnosis, therapy, and prevention of central nervous system (CNS) disorders. In recent years, several types of research have improved our insight into CSF and its role in health and disease. Yet, many characteristics of this fluid remain to be fully understood. NEW METHODS: Here, we describe how to collect CSF from embryonic, postnatal, and adult stages of the rat. In adults, CSF can be collected through simple stereotaxic surgery to expose the membrane overlying the cisterna magna (CM) of an anesthetized rat and collection of CSF through micropipette puncture through the membrane. In embryos and pups, CSF is aspirated, using a fire-polished micro-capillary pipette, from the CM of animals. RESULTS: Application of these methods provides the maximum volume of pure, uncontaminated CSF (embryonic day 19: 10-15 microliter, postnatal day 5: 20-30 microliter, adults: 100-200 microliter) with a success rate of approximately 95% in every age. COMPARISON WITH EXISTING METHODS: Compared to the existing protocols, these methods obtain considerable volumes of CSF, which may accelerate the measurement of biological markers in this fluid. Also, these techniques do not require surgical skills and according to the practical points mentioned during sampling, the procedures can be performed in rapid fashion. CONCLUSION: We describe simple methods for collecting CSF in live rats. These protocols provide clean, uncontaminated CSF for experiments to understand the exact role of this fluid in the development and maintenance of the CNS health.

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells.

The beneficial effects of hair follicle stem cells in different animal models of nervous system conditions have been extensively studied. While chick embryo extract (CEE) has been used as a growth medium supplement for these stem cells, this is the first study to show the effect of CEE on them. The rat hair follicle stem cells were isolated and supplemented with 10% fetal bovine serum plus 10% CEE. The migration rate, proliferative capacity and multipotency were evaluated along with morphometric alteration and differentiation direction. The proteome analysis of CEE content identified effective factors of CEE that probably regulate fate and function of stem cells. The CEE enhances the migration rate of stem cells from explanted bulges as well as their proliferation, likely due to activation of AP-1 and translationally controlled tumour protein (TCTP) by thioredoxin found in CEE. The increased length of outgrowth may be the result of cyclic AMP response element binding protein (CREB) phosphorylation triggered by active CamKII contained in CEE. Further, CEE supplementation upregulates the expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. The elevated expression of target genes and proteins may be due to CREB, AP-1 and c-Myc activation in these stem cells. Given the increased transcript levels of neurotrophins, VEGF, and the expression of PDGFR-α, S100B, MBP and SOX-10 protein, it is possible that CEE promotes the fate of these stem cells towards Schwann cells.

Intranasal application of stem cells and their derivatives as a new hope in the treatment of cerebral hypoxia/ischemia: a review.

Intranasal delivery of stem cells and conditioned medium to target the brain has attracted major interest in the field of regenerative medicine. In pre-clinical investigations during the last ten years, several research groups focused on this strategy to treat cerebral hypoxia/ischemia in neonates as well as adults. In this review, we discuss the curative potential of stem cells, stem cell derivatives, and their delivery route via intranasal application to the hypoxic/ischemic brain. After intranasal application, stem cells migrate from the nasal cavity to the injured area and exert therapeutic effects by reducing brain tissue loss, enhancing endogenous neurogenesis, and modulating cerebral inflammation that leads to functional improvements. However, application of this administration route for delivering stem cells and/or therapeutic substances to the damaged sites requires further optimization to translate the findings of animal experiments to clinical trials.

Cerebral Folate Metabolism in Post-Mortem Alzheimer's Disease Tissues: A Small Cohort Study.

We investigated the cerebral folate system in post-mortem brains and matched cerebrospinal fluid (CSF) samples from subjects with definite Alzheimer's disease (AD) (n = 21) and neuropathologically normal brains (n = 21) using immunohistochemistry, Western blot and dot blot. In AD the CSF showed a significant decrease in 10-formyl tetrahydrofolate dehydrogenase (FDH), a critical folate binding protein and enzyme in the CSF, as well as in the main folate transporter, folate receptor alpha (FRα) and folate. In tissue, we found a switch in the pathway of folate supply to the cerebral cortex in AD compared to neurologically normal brains. FRα switched from entry through FDH-positive astrocytes in normal, to entry through glial fibrillary acidic protein (GFAP)-positive astrocytes in the AD cortex. Moreover, this switch correlated with an apparent change in metabolic direction to hypermethylation of neurons in AD. Our data suggest that the reduction in FDH in CSF prohibits FRα-folate entry via FDH-positive astrocytes and promotes entry through the GFAP pathway directly to neurons for hypermethylation. This data may explain some of the cognitive decline not attributable to the loss of neurons alone and presents a target for potential treatment.

The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: a Review.

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments.

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit theburden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity.

Profound changes in cerebrospinal fluid proteome and metabolic profile are associated with congenital hydrocephalus.

The aetiology of congenital hydrocephalus (cHC) has yet to be resolved. cHC manifests late in rodent gestation, and by 18-22 weeks in human fetuses, coinciding with the start of the major phase of cerebral cortex development. Previously we found that cerebrospinal fluid (CSF) accumulation is associated with compositional changes, folate metabolic impairment and consequential arrest in cortical development. Here, we report a proteomics study on hydrocephalic and normal rat CSF using LC-MSMS and a metabolic pathway analysis to determine the major changes in metabolic and signalling pathways. Non-targeted analysis revealed a proteome transformation across embryonic days 17-20, with the largest changes between day 19 and 20. This provides evidence for a physiological shift in CSF composition and identifies some of the molecular mechanisms unleashed during the onset of cHC. Top molecular regulators that may control the shift in the CSF metabolic signature are also predicted, with potential key biomarkers proposed for early detection of these changes that might be used to develop targeted early therapies for this condition. This study confirms previous findings of a folate metabolic imbalance as well as providing more in depth metabolic analysis and understanding of cHC CSF.

The Implementation of Preconditioned Epidermal Neural Crest Stem Cells to Combat Ischemic Stroke. Comment on Othman, F.A.; Tan, S.C. Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke. Brain Sci. 2020, 10, 893.

In the recent review published in Brain Sciences, Othman and Tan suggested several preconditioning strategies to improve stem cell therapy after ischemic brain injury [...].

Prevalence of metabolic syndrome in primary health settings in Qatar: a cross sectional study.

BACKGROUND: In Qatar, prevalence of metabolic components is significantly higher compared to other countries. It is therefore urgent to understand the prevalence of metabolic syndrome (MetS) with the goal of identifying etiologic factors in Qatar. This study was undertaken to estimate the prevalence of MetS, by age, gender and nationality within primary care settings in Qatar. In addition, it determined the independent effects of risk factors on the prevalence of MetS. METHODS: A cross-sectional study design was used. Data for individuals aged ≥18 and who visited a publicly funded primary health centre in Qatar during 2017 were extracted from electronic medical records and analysed. RESULTS: The findings showed that the prevalence of individual MetS components ranged between 48.5-60.3%. Overall prevalence of MetS was 48.8% (N = 62,492) in the study population. Prevalence of MetS increased with age. 50.3% of the population within the 40-49 year age group had MetS. In this age band, individuals were 5.1 times more likely of having MetS compared to the 18-29 year age group. MetS was slightly more prevalent in men (56 .7%) compared to women (42.5%). However, men were 1.33 times more likely of having MetS compared to women. The prevalence of MetS ranged between 20.6 - 60% across nationalities. It was most prevalent in Southern Asians (60%), followed by Northern Africans (50.7%) and Western Asians (excluding Qatar) (46.8%). Prevalence of MetS in Qataris was 43%. Southern Asians, Northern African and Western Asians were 1.73, 1.38 and 1.17 more likely to have MetS compared to Qataris. CONCLUSIONS: The study provides essential epidemiological information required by decision makers. Although not nationally representative, this study is suggestive of a higher prevalence of MetS among a younger population, men and in Southern Asian, Northern African and Western Asian nationalities. Prevention, treatment and control of MetS is a public health problem in Qatar. More studies are needed to establish which public health interventions are likely to be effective in Qatar.

Vitamin D status among adults (18-65 years old) attending primary healthcare centres in Qatar: a cross-sectional analysis of the Electronic Medical Records for the year 2017.

OBJECTIVES: To investigate the prevalence of vitamin D deficiency among individuals attending primary healthcare facilities in Qatar and to assess the association between vitamin D deficiency and some medical conditions in persons aged 18-65 years old. SETTING: The study was undertaken in publicly funded primary healthcare services in the State of Qatar. PARTICIPANTS: A total of 102 342 participants aged between 18 and 65 years old with a valid serum vitamin D test result during the year 2017. OUTCOME MEASURES: Serum level <10 ng/mL (<25 nmol/L) was defined as severe vitamin D deficiency, a serum level of <20 ng/mL (<50 nmol/L) was defined as vitamin D deficiency and a serum level <30 ng/mL (<75 nmol/L) defined as vitamin D insufficiency. RESULTS: The prevalence rate of severe vitamin D deficiency was 14.1% among study participants with no history of vitamin D replacement therapy in the previous months. The prevalence rate of vitamin D deficiency was as high as 71.4% and that of vitamin D insufficiency was up to 92.7%. None of the five chronic conditions explored in the study (diabetes, hypertension, asthma, stroke and cardiovascular disease) had an obvious association with severe vitamin D deficiency status in a bivariate analysis. However, multivariate modelling showed that (adjusting for age, gender, body mass index and nationality and each of the included chronic conditions) hypertension, cardiovascular diseases and stroke placed an individual at a higher risk of having an associated severe vitamin D deficiency status. CONCLUSION: Although not comprehensive and nationally representative, this study is suggestive of a higher prevalence of vitamin D deficiency among young adults, females, Qatari nationality and those with higher body mass index. Multivariate modelling showed that hypertension, cardiovascular diseases and stroke were associated with a higher risk of severe vitamin D deficiency status.

Molecular Informatics Studies of the Iron-Dependent Regulator (ideR) Reveal Potential Novel Anti-Mycobacterium ulcerans Natural Product-Derived Compounds.

Buruli ulcer is a neglected tropical disease caused by the bacterium Mycobacterium ulcerans. Its virulence is attributed to the dermo-necrotic polyketide toxin mycolactone, whose synthesis is regressed when its iron acquisition system regulated by the iron-dependent regulator (ideR) is deactivated. Interfering with the activation mechanism of ideR to inhibit the toxin's synthesis could serve as a possible cure for Buruli ulcer. The three-dimensional structure of the ideR for Mycobacterium ulcerans was generated using homology modeling. A library of 832 African natural products (AfroDB), as well as five known anti-mycobacterial compounds were docked against the metal binding site of the ideR. The area under the curve (AUC) values greater than 0.7 were obtained for the computed Receiver Operating Characteristics (ROC) curves, validating the docking protocol. The identified top hits were pharmacologically profiled using Absorption, Distribution, Metabolism, Elimination and Toxicity (ADMET) predictions and their binding mechanisms were characterized. Four compounds with ZINC IDs ZINC000018185774, ZINC000095485921, ZINC000014417338 and ZINC000005357841 emerged as leads with binding energies of -7.7 kcal/mol, -7.6 kcal/mol, -8.0 kcal/mol and -7.4 kcal/mol, respectively. Induced Fit Docking (IFD) was also performed to account for the protein's flexibility upon ligand binding and to estimate the best plausible conformation of the complexes. Results obtained from the IFD were consistent with that of the molecular docking with the lead compounds forming interactions with known essential residues and some novel critical residues Thr14, Arg33 and Asp17. A hundred nanoseconds molecular dynamic simulations of the unbound ideR and its complexes with the respective lead compounds revealed changes in the ideR's conformations induced by ZINC000018185774. Comparison of the lead compounds to reported potent inhibitors by docking them against the DNA-binding domain of the protein also showed the lead compounds to have very close binding affinities to those of the potent inhibitors. Interestingly, structurally similar compounds to ZINC000018185774 and ZINC000014417338, as well as analogues of ZINC000095485921, including quercetin are reported to possess anti-mycobacterial activity. Also, ZINC000005357841 was predicted to possess anti-inflammatory and anti-oxidative activities, which are relevant in Buruli ulcer and iron acquisition mechanisms, respectively. The leads are molecular templates which may serve as essential scaffolds for the design of future anti-mycobacterium ulcerans agents.

Altered folate binding protein expression and folate delivery are associated with congenital hydrocephalus in the hydrocephalic Texas rat.

Hydrocephalus (HC) is an imbalance in cerebrospinal fluid (CSF) secretion/absorption resulting in fluid accumulation within the brain with consequential pathophysiology. Our research has identified a unique cerebral folate system in which depletion of CSF 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is associated with cortical progenitor cell-cycle arrest in hydrocephalic Texas (H-Tx) rats. We used tissue culture, immunohistochemistry, in-situ PCR and RT-PCR and found that the in-vitro proliferation of arachnoid cells is highly folate-dependent with exacerbated proliferation occurring in hydrocephalic CSF that has low FDH but high folate-receptor-alpha (FRα) and folate. Adding FDH to this CSF prevented aberrant proliferation indicating a regulatory function of FDH on CSF folate concentration. Arachnoid cells have no detectable mRNA for FRα or FDH, but FDH mRNA is found in the choroid plexus (CP) and CSF microvesicles. Co-localization of FDH, FRα and folate suggests important functions of FDH in cerebral folate transport, buffering and function. In conclusion, abnormal CSF levels of FDH, FRα and folate inhibit cortical cell proliferation but allow uncontrolled arachnoid cell division that should increase fluid absorption by increasing the arachnoid although this fails in the hydrocephalic brain. FDH appears to buffer available folate to control arachnoid proliferation and function.

Iron deficiency, its epidemiological features and feeding practices among infants aged 12 months in Qatar: a cross-sectional study.

OBJECTIVES: To estimate the magnitude of anaemia, iron deficiency (ID), iron deficiency anaemia (IDA) and to explore epidemiological features of ID and feeding practices among infants aged 12 months in Qatar. SETTING: Well baby clinics in 14 randomly selected primary healthcare centres covering all geographical areas on the national level. PARTICIPANTS: Three hundred and six (163 male and 143 female) infants of all nationalities were enrolled. Mothers were asked to complete a predesigned interview questionnaire and infants were blood tested for anaemia, ID and IDA. OUTCOME MEASURES: Cut-off point used to diagnose anaemia was haemoglobin <11.1 g/dL, and to diagnose ID, serum ferritin <6 ug/L with normal C reactive protein. RESULTS: Prevalence of anaemia was 23.5%, ID was 9.2% and IDA was 7.8%. ID was more prevalent among non-Qatari infants compared with Qatari (10.9% vs1.7%, p=0.029), more prevalent among infants born to housewives and to families of low income (p≤0.05). With regard to feeding practice, ID was higher in infants who continued breastfeeding until the age of 1 year and among those who never took infant formula milk (p≤0.05). Mothers who received infant feeding counselling had less ID occurrence among their infants compared with their counterparts who did not receive such counselling (4.2%vs13.4%, p=0.005). CONCLUSION: Although ID and IDA among infants in Qatar are less prevalent compared with many developing countries, still further efforts are needed for improvement towards more developed countries. Efforts should be contextualised and should target the key epidemiological features with special emphasis on infant feeding and infant feeding counselling to mothers.

In Vitro Effects of Wistar Rat Prenatal and Postnatal Cerebrospinal Fluid on Neural Differentiation and P roliferation of Mesenchymal Stromal Cells Derived from Bone Marrow.

OBJECTIVES: Cerebrospinal fluid (CSF) plays an important role in cortical development during the fetal stages. Embryonic CSF (E-CSF) consists of numerous neurotrophic and growth factors that regulate neurogenesis, differentiation, and proliferation. Mesenchymal stem cells (MSCs) are multi-potential stem cells that can differentiate into mesenchymal and non-mesenchymal cells, including neural cells. This study evaluates the prenatal and postnatal effects of CSF on proliferation and neural differentiation of bone marrow MSCs (BM-MSCs) at gestational ages E19, E20, and the first day after birth (P1). MATERIALS AND METHODS: In this experimental study, we confirmed the mesenchymal nature of BM-MSCs according to their adherence properties and surface markers (CD44, CD73 and CD45). The multi-potential characteristics of BMMSCs were verified by assessments of the osteogenic and adipogenic potentials of these cells. Under appropriate in vitro conditions, the BM-MSCs cultures were incubated with and without additional pre- and postnatal CSF. The MTT assay was used to quantify cellular proliferation and viability. Immunocytochemistry was used to study the expression of MAP-2 and ß-III tubulin in the BM-MSCs. We used ImageJ software to measure the length of the neurites in the cultured cells. RESULTS: BM-MSCs differentiated into neuronal cell types when exposed to basic fibroblast growth factor (b-FGF). Viability and proliferation of the BM-MSCs conditioned with E19, E20, and P1 CSF increased compared to the control group. We observed significantly elevated neural differentiation of the BM-MSCS cultured in the CSF-supplemented medium from E19 compared to cultures conditioned with E20 and P1 CSF group. CONCLUSIONS: The results have confirmed that E19, E20, and P1 CSF could induce proliferation and differentiation of BM-MSCs though they are age dependent factors. The presented data support a significant, conductive role of CSF components in neuronal survival, proliferation, and differentiation.

Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

Fetal Cerebrospinal Fluid Promotes Proliferation and Neural Differentiation of Stromal Mesenchymal Stem Cells Derived from Bone Marrow

ABSTRACT Embryonic cerebrospinal fluid (E-CSF) contains many neurotrophic and growth factors, acts as a growth medium for cortical progenitors, and can modulate proliferation and differentiation of neural stem cells. Mesenchymal stem cells (MSCs) are multipotential stem cells that can differentiate into several types of mesenchymal cells as well as nonmesenchymal cells, such as neural cells. In the present study, the effect of E-CSF on proliferation and neural differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was investigated to test whether E-CSF is capable of driving these cells down the neuronal line. To verify the multipotential characteristics of BM-MSCs, the cells were analyzed for their osteogenic and adipogenic potential. Expression of the neural markers, MAP-2 and β-III tubulin, was determined by Immunocytochemistry. BM-MSCs differentiate into neuronal cell types when exposed to b-FGF. BMMSCs cells cultured in medium supplemented with CSF showed significantly elevated proliferation relative to control cells in media alone. E-CSF (E17-E19) supports viability and stimulates proliferation and, significantly, neurogenic differentiation of BM-MSCs. The data presented support an important role for CSF components, specifically neurotrophic factors, in stem cell survival, proliferation and neuronal differentiation. It is crucial to understand this control by CSF to ensure success in neural stem cell therapies.

Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis.

Neuro-immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium-channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin-gene-related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well-documented 'neural' ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen-presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down-regulation of activation markers CD80/86 on dendritic cells, and up-regulation of interleukin-6 and interleukin-10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis.