Neurotensin receptor 2 is induced in astrocytes and brain endothelial cells in relation to neuroinflammation following pilocarpine‐induced seizures in rats

Abstract

Neurotensin (NT) acts as a primary neurotransmitter and neuromodulator in the CNS and has been involved in a number of CNS pathologies including epilepsy. NT mediates its central and peripheral effects by interacting with the NTSR1, NTSR2, and Sort1/NTSR3 receptor subtypes. To date, little is known about the precise expression of the NT receptors in brain neural cells and their regulation in pathology. In the present work, we studied the cellular distribution of the NTSR2 protein in the rat hippocampus and questioned whether its expression was modulated in conditions of neuroinflammation using a model of temporal lobe epilepsy induced by pilocarpine. This model is characterized by a rapid and intense inflammatory reaction with reactive gliosis in the hippocampus. We show that NTSR2 protein is expressed in hippocampal astrocytes and its expression increases together with astrocyte reactivity following induction of status epilepticus. NTSR2 immunoreactivity is also increased in astrocytes proximal to blood vessels and their end-feet, and in endothelial cells.Proinflammatory factors such as IL1β and LPS induced NTSR2 mRNA and protein in cultured astroglial cells. Antagonizing NTSR2 with SR142948A decreased NTSR2 expression as well as astroglial reactivity. Together, our results suggest that NTSR2 is implicated in astroglial and gliovascular inflammation and that targeting the NTSR2 receptor may open new avenues in the regulation of neuroinflammation in CNS diseases.

Deciphering the Association of Epstein–Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice

“…NTSR2 is expressed in the hippocampal astrocytes, and its expression increases together with astrocyte reactivity. Previously, NTSR2 has been implicated in the astroglia and gliovascular inflammation, which could be a potent therapeutic target . Thus, these data highlighted the changes in the level of NTSR2 that can further be corroborated with the increased inflammatory moieties.…”

Overexpression of a Novel Noxo1 Mutant Increases Ros Production and Noxo1 Relocalisation

“…Transfected Caco-2 cells with wt Noxo1 or mut1 Noxo1 were fractionated into cytosolic, membrane, and cytoskeleton fractions using a cell fractionation kit, and the same amounts (35 µg) of these fractions were analyzed by Western blot for specific markers: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as cytosolic and membrane marker [26][27][28] and alpha Na,K-ATPase as a membrane marker [29]. GAPDH, and alpha Na,K-ATPase proteins were detected as a single band with molecular weights of 38 and 100 kDa, respectively, in transfected Caco-2 cells.…”

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

“…Support for the hypothesis that inflammation contributes to ictogenesis comes from rodent models of pilocarpineinduced, kainic acid-induced, and pentylenetetrazoleinduced seizure propensities that include a robust inflammatory response. [64][65][66][67][68][69][70] Anti-inflammatory approaches involving inhibition of prostaglandin EP2 receptors, 65,66 inhibition of mTOR signaling, 64 and inhibition of neurotensin receptor 2 reduce the inflammation-associated phenomena (including seizure occurrence) attributed to pilocarpine, and thus offer support for the hope that these anti-inflammatory approaches might reduce seizure occurrence in humans.…”