Lymphocyte-mediated neuroprotection in in vitro models of excitotoxicity involves astrocytic activation and the inhibition of MAP kinase signalling pathways

Rajeev Shrestha Maleku, Owain Millington, James Brewer, Kumlesh Dev, Trevor Bushell

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

It is well established that immunosurveillance is active in the CNS and plays a key role in several CNS disorders but the exact role of immune cells remains elusive. Thus, in the present study we investigated whether lymphocytes are protective/detrimental in in vitro models of excitotoxicty. Kainate (KA)-induced neuronal death was significantly reduced following exposure to mixed lymphocytes or purified T lymphocytes containing either activated or non-activated T-lymphocytes. Conditioned media from lymphocyte preparations, but not boiled conditioned media, was protective against KA-induced toxicity indicating soluble mediators underlie the observed neuroprotection with cytokine arrays indicating IL-16 as the likely candidate. A role for astrocytes was established as the neuroprotection was abolished in the presence of the glial toxin, fluoroacetate. Furthermore, lymphocytes inhibited p38 MAPK and ERK signalling pathways with pharmacological inhibition of these pathways mimicking the protective effect of lymphocytes. Similarly, lymphocytes were neuroprotective against oxygen-glucose deprivation (OGD)-induced cell death with the inhibition of p38 MAPK and ERK signalling pathways involved. These data indicate that lymphocytes are neuroprotective under our experimental conditions and we suggest that astrocytic activation and inhibition of MAPK signalling cascades are involved but further studies are required to investigate whether similar mechanisms underlie the actions of lymphocytes in in vivo experimental models of disease. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

LanguageEnglish
Pages184-193
Number of pages10
JournalNeuropharmacology
Volume76
Issue numberA
Early online date4 Jul 2013
DOIs
Publication statusPublished - Jan 2014

Fingerprint

MAP Kinase Signaling System
Lymphocytes
Kainic Acid
p38 Mitogen-Activated Protein Kinases
Conditioned Culture Medium
Fluoroacetates
Interleukin-16
T-Lymphocytes
Immunologic Monitoring
In Vitro Techniques
Neuroprotection
Neuroglia
Astrocytes
Neurodegenerative Diseases
Cell Death
Theoretical Models
Pharmacology
Cytokines
Oxygen
Glucose

Keywords

  • astrocytes
  • lymphocytes
  • MAP kinases
  • neuroinflammation
  • neuroprotection
  • T cells

Cite this

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title = "Lymphocyte-mediated neuroprotection in in vitro models of excitotoxicity involves astrocytic activation and the inhibition of MAP kinase signalling pathways",
abstract = "It is well established that immunosurveillance is active in the CNS and plays a key role in several CNS disorders but the exact role of immune cells remains elusive. Thus, in the present study we investigated whether lymphocytes are protective/detrimental in in vitro models of excitotoxicty. Kainate (KA)-induced neuronal death was significantly reduced following exposure to mixed lymphocytes or purified T lymphocytes containing either activated or non-activated T-lymphocytes. Conditioned media from lymphocyte preparations, but not boiled conditioned media, was protective against KA-induced toxicity indicating soluble mediators underlie the observed neuroprotection with cytokine arrays indicating IL-16 as the likely candidate. A role for astrocytes was established as the neuroprotection was abolished in the presence of the glial toxin, fluoroacetate. Furthermore, lymphocytes inhibited p38 MAPK and ERK signalling pathways with pharmacological inhibition of these pathways mimicking the protective effect of lymphocytes. Similarly, lymphocytes were neuroprotective against oxygen-glucose deprivation (OGD)-induced cell death with the inhibition of p38 MAPK and ERK signalling pathways involved. These data indicate that lymphocytes are neuroprotective under our experimental conditions and we suggest that astrocytic activation and inhibition of MAPK signalling cascades are involved but further studies are required to investigate whether similar mechanisms underlie the actions of lymphocytes in in vivo experimental models of disease. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.",
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author = "{Shrestha Maleku}, Rajeev and Owain Millington and James Brewer and Kumlesh Dev and Trevor Bushell",
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Lymphocyte-mediated neuroprotection in in vitro models of excitotoxicity involves astrocytic activation and the inhibition of MAP kinase signalling pathways. / Shrestha Maleku, Rajeev; Millington, Owain; Brewer, James; Dev, Kumlesh; Bushell, Trevor.

In: Neuropharmacology, Vol. 76, No. A, 01.2014, p. 184-193.

Research output: Contribution to journalArticle

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