Modifications in neurotrophins, neuropeptides, cytokines and nitric oxide (NO) levels in autism may represent different biological aspects of the disease. In the present study we investigate ...simultaneously all these variables as an attempt to clarify their interrelationships in autism.
Plasma levels of vasoactive intestinal peptide (VIP), neurotrophin-3 (NT-3), cytokines and nitric oxide (NO) were determined in children with DSM-IV autistic disorder (n = 24) and in age- and gender-matched healthy controls (n = 24). VIP, NT-3, IFN-γ and IL-1β levels were measured by ELISA, TNF-α, IL-10, IL-6, IL-4, IL-2 were evaluated by fl ow cytometry, and NO by Griess reaction.
Plasma levels of VIP, IFN-γ and NO were significantly higher and NT-3 plasma levels were significantly lower in children with autism, compared to the healthy subjects. In children with autism there was a positive correlation between plasma levels of NO and IFN-γ.
Our results indicate the presence of altered levels of neurotrophin and neuropeptide in infantile autism and provide additional evidence that higher levels of IFN-γ may be associated with increased oxidative stress in autism.
Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, ...suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons are known to contact other interneurons and excitatory cells and are thus capable of providing a local disinhibitory mechanism, yet little is known about this cell type in the MEC. To investigate the electrophysiological and morphological properties of VIP cells in the MEC, we use
whole-cell patch-clamp recordings in VIPcre/tdTom mice. We report several gradients in electrophysiological properties of VIP cells that differ across laminae and along the dorsal-ventral MEC axis. We additionally show that VIP cells have distinct morphological features across laminae. Together, these results characterize the cellular and morphological properties of VIP cells in the MEC.
Pharmacogenomic studies of different ethnic or racial groups have been used to develop personalized therapies specific to subjects. This study aimed to identify the distribution differences of very ...important pharmacogenetic (VIP) variants between the Lisu population from southwestern China and other ethnic groups.Eighty VIP variants in 37 genes were selected from the pharmacogenomic knowledge base (PharmGKB), and compared with genotype data of the Lisu population then compared with other 11 populations from the HapMap dataset and previously published data including Miao, Li, Deng, Sherpa, Lhoba, Tibetan, Kirghiz, Tajik, Mongol, Shaanxi Han ethnic, and Uygur populations.VDR rs1540339, MTHFR rs1801131, P2RY1 rs701265, and PTGS2 rs689466 were significantly different between Lisu and 11 HapMap populations. ANKK1 rs1800497 was the least statistical significant locus among selected single nucleotide polymorphisms. In addition, genetic background of Lisu was strongly closest to Shaanxi Han ethnic cohort, and followed by Chinese in metropolitan Denver population based on population structure and F-statistics analyses.Our results showed significant interethnic differences between Lisu and other populations, which will give useful information for prospective studies and better individualized treatments.
Background
Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented.
Aims
To determine the distribution and projection ...sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene‐related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild‐type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice. Furthermore, to identify the location and neurochemical coding of the spinal afferent nerve endings in the urethra, whose sensory neurons reside in lumbosacral dorsal root ganglia (DRG).
Methods
Multiple labeling immunohistochemistry of urethral sections of nulliparous (6‐8 weeks old), and multiparous (9‐12 months old) mice, and anterograde axonal tracing from L5‐S2 (DRG) in vivo.
Results
Abundant VIP‐, CGRP‐, SP‐, and NPY‐immunoreactive nerve fibers were identified in the adventitia, muscularis, and lamina propria of proximal and distal segments of the urethra. A proportion of fibers were closely associated with blood vessels, glands, and cells immunoreactive for PGP9.5. The epithelium contained abundant nerve fibers immunoreactive for CGRP and/or SP. Epithelial innervation was increased in the distal urethra of multipara mice. Abundant fibers were traced from L5‐S2 DRG to all urethral regions.
Conclusions
We present the first identification of spinal afferent endings in the urethra. Peptidergic nerve fibers, including multiple populations of spinal afferents, provide rich innervation of the female mouse urethra. The morphology of fibers in the epithelium and other regions suggests multiple nerve‐cell interactions impacting on urethral function.
It is now evident that acetylcholine (ACh) synthesized by choline acetyltransferase (ChAT) and released from T cells during antigen presentation binds to muscarinic and nicotinic ACh receptors ...(mAChRs and nAChRs, respectively) on T and B cells or dendritic cells, leading to modulation of their function. In the present study, we used reverse transcription-polymerase chain reaction (RT-PCR) to investigate whether mononuclear leukocytes (MNLs), bone marrow-derived dendritic cells (DCs) and macrophages from C57BL/6J mice express components of the cholinergic system. Expression of ChAT mRNA was detected in MNLs activated with ConA and DCs stimulated with LPS, but not in resting MNLs and DCs or in resting and stimulated macrophages. MNLs, DCs and macrophages all expressed mRNAs encoding the five mAChR subtypes (M1–M5) and the nAChR α2, α5, α6, α7, α10 and β2 subunits. Expression of VIP mRNA was detected in MNLs and macrophages, but not in DCs. MNLs, DCs and macrophages all expressed VIP receptor-1 (VPAC1) and -2 (VPAC2) mRNAs, as well as mRNAs encoding secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP)-1 and SLURP-2, two endogenous nAChR ligands. These results suggest that the lymphocytic cholinergic system is activated by ACh via mAChR- and nAChR-mediated pathways during antigen presentation between T cells and DCs or macrophages, leading to modulation of immune cell function. Moreover, VIP released from both postganglionic cholinergic neurons and immune cells may play a role in the cholinergic anti-inflammatory reflex, acting via VPAC1 and VPAC2 on immune cells.
Th17 cells from eRA patients are prone to expand to a pathological cell population under Th17‐polarizing conditions where VIP prevents their pathogenesis.
Several studies in humans indicate the ...implication of Th17 cells in RA. Therapies targeting their pathogenicity, as well as their plasticity to the Th17/1 phenotype, could ameliorate the progression of the pathology. The neuroendocrine environment has a major impact on the differentiation of lymphoid cells. VIP is present in the microenvironment of the joint, and its known therapeutic effects are supported by several studies on RA. We examine the ability of VIP to modulate the differentiation of Th17 cells. Peripheral blood CD4+CD45RO+ T cells from HD and eRA patients were expanded under Th17‐polarizing conditions in the presence of TGF‐β. After 7 days, the higher IL‐17A, IL‐21, and IL‐9 levels and lower IL‐22 levels indicate the nonpathogenic profile for Th17 cells in HD. In contrast, Th17 cells from eRA patients produced significantly more IL‐22 and IFN‐γ, and these cells show a more Th17/1 profile, indicating a pathogenic phenotype. Interestingly, when VIP was present in the Th17 conditioned medium, increased levels of IL‐10 and IL‐9 were detected in HD and eRA patients. VIP also reduced the levels of IL‐22 in eRA patients. These data suggest that VIP reduces the pathogenic profile of the Th17‐polarized cells. This effect was accompanied by an increased in the Treg/Th17 profile, as shown by the increase levels of Foxp3. In conclusion, this report addresses a novel and interesting question on the effect of VIP on human Th17 cells and adds clinical relevance by analyzing, in parallel, HD and eRA patients.
A high-performance insulation solution, such as vacuum insulation panel (VIP) reduces heat losses in a retrofitted building envelope. However, discontinuity of insulation material causes thermal ...bridges. A significant thermal bridge effect at the edge of VIP must be taken into account in the overall heat transfer coefficient (U-value) calculation; but is often omitted due to difficulties especially with numerical calculations. This study describes a modeling approach used to accurately evaluate the effect of thermal bridges on the overall U-value of building envelope. The thermal bridge and U-value were modeled and computed respectively using DesignBuilder which is based on EnergyPlus dynamic simulation engine. Correlation was drawn between experimentally determined U-value of VIP retrofitted building walls and the principal computation parameter.
The mammalian target of rapamycin (mTOR) signaling pathway is a powerful regulator of cell proliferation, growth, synapse maintenance and cell fate. While intensely studied for its role in cancer, ...the role of mTOR signaling is just beginning to be uncovered in specific cell types that are implicated in neurodevelopmental disorders. Previously, loss of the
gene, which results in hyperactive mTOR, was shown to affect the function and molecular properties of GABAergic cortical interneurons (CINs) derived from the medial ganglionic eminence. To assess if other important classes of CINs could be impacted by mTOR dysfunction, we deleted
in a caudal ganglionic eminence-derived interneuron group, the vasoactive intestinal peptide (VIP)+ subtype, whose activity disinhibits local circuits.
mutant VIP+ CINs reduced their pattern of apoptosis from postnatal days 15-20, resulting in increased VIP+ CINs. The mutant CINs exhibited synaptic and electrophysiological properties that could contribute to the high rate of seizure activity in humans that harbor
mutations.
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