کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5630093 1580362 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning
چکیده انگلیسی


- LPS increase kynurenic acid (KYNA) in medial prefrontal-cortex (mPFC).
- LPS increase p-neurogranin and lowers p-CaMKII in the mPFC.
- Dysregulated p-CaMKII and Nrgn-NFAT signaling is associated with impaired Pavlovian conditioning.
- Kynurenine monooxygenase inhibition increases p-Nrgn and dampens p-CaMKII in the mPFC.
- Glutamatergic KYNA-Nrgn signaling is associated with cognitive dysfunction.

The N-Methyl-d-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-II (CaMKII). We confirmed that systemic blockade of kynurenine-3 monooxygenase in conjunction with kynurenine administration results in significant increases in Nrgn phosphorylation and a significant reduction of CaMKII phosphorylation in the mPFC. Consequently, dual-LPS administration induced significant impairments in stimulus processing during Pavlovian conditioning. Taken together, our study indicates that elevations in KYNA in the mPFC can directly regulate NMDA-Nrgn-CaMKII signaling, suggesting that neuroinflammatory conditions affecting this pathway may be associated with cognitive dysfunction.

118

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Neuroimmunology - Volume 313, 15 December 2017, Pages 1-9
نویسندگان
, , , , , , , , , , ,