کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7280832 | 1473918 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: Pathophysiological and neurobehavioral implications
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کلمات کلیدی
CREBPIP2post-synaptic density 95IP3NMDAN-methyl-d-aspartatePSD95PKCGKAPinositol 1,4,5 trisphosphate - inositol 1،4،5 trisphosphateMAPK - MAPKStereology - استریولوژیNeuroinflammation - التهاب عصبیAutism - اوتیسم یا درخودماندگیdiacylglycerol - دیسیل گلیسیرینDAG - روزShank3 - شانک 3endoplasmic reticulum - شبکه آندوپلاسمی phosphatidylinositol 4,5-bisphosphate - فسفاتیدیلینوزیتول 4،5-بیسفسفاتMicroglia - میکروگلیاهاneuropathology - نوروپاتولوژی یا آسیب شناسی عصبیProtein kinase C - پروتئین کیناز سیmitogen activated protein kinase - پروتئین کیناز فعال Mitogen فعال استglutamate - گلوتامات
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Metabotropic glutamate receptor 5 (mGluR5) and microglial abnormalities have been implicated in autism spectrum disorder (ASD). However, controversy exists as to whether the receptor is down or upregulated in functioning in ASD. In addition, whilst activation of mGluR5 has been shown to attenuate microglial activation, its role in maintaining microglial homeostasis during development has not been investigated. We utilised published microarray data from the dorsolateral prefrontal cortex (DLPFC) of control (n = 30) and ASD (n = 27) individuals to carry out regression analysis to assess gene expression of mGluR5 downstream signalling elements. We then conducted a post-mortem brain stereological investigation of the DLPFC, to estimate the proportion of mGluR5-positive neurons and glia. Finally, we carried out stereological investigation into numbers of microglia in mGluR5 knockout mice, relative to wildtype littermates, together with assessment of changes in microglial somal size, as an indicator of activation status. We found that gene expression of mGluR5 was significantly decreased in ASD versus controls (p = 0.018) as well as downstream elements SHANK3 (p = 0.005) and PLCB1 (p = 0.009) but that the pro-inflammatory marker NOS2 was increased (p = 0.047). Intensity of staining of mGluR5-positive neurons was also significantly decreased in ASD versus controls (p = 0.016). Microglial density was significantly increased in mGluR5 knockout animals versus wildtype controls (p = 0.011). Our findings provide evidence for decreased expression of mGluR5 and its signalling components representing a key pathophysiological hallmark in ASD with implications for the regulation of microglial number and activation during development. This is important in the context of microglia being considered to play key roles in synaptic pruning during development, with preservation of appropriate connectivity relevant for normal brain functioning.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 49, October 2015, Pages 197-205
Journal: Brain, Behavior, and Immunity - Volume 49, October 2015, Pages 197-205
نویسندگان
Gursharan Chana, Liliana Laskaris, Christos Pantelis, Piers Gillett, Renee Testa, Daniela Zantomio, Emma L. Burrows, Anthony J. Hannan, Ian P. Everall, Efstratios Skafidas,