Publication: Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration
Date
2013
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Kathmandu University
Abstract
ABSTRACT
Background
Neurodegenerative disease is a progressive loss of neurons from the central nervous
system (CNS). Various conditions have been implicated for such conditions including
ageing, inflammation, stress and genetic predisposition. Recently, studies have
linked neurodegeneration with inflammation. Some studies have suggested the
harmful effect of immune response while others have argued its neuroprotective
role in neurodegeneration of the CNS. However, the precise role of inflammation
and immune cells in such condition is still not clear.
Objective
To investigate the role of lymphocytes in neurodegeneration of the CNS and
determine the underlying mechanism.
Method
We have used 4-7 days old mouse pups (C57Bl6) to prepare organotypic slice cultures
which were cultured for 13-15 days prior to experiment. To induced cell death
kainic acid was used and considered as an in vitro model for neurodegeneration.
Lymphocytes were obtained from peripheral lymph nodes of 5-10 weeks old adult
mouse which were used in the current study. Propidium iodide was used as a
fluorescent dye to determine cell death in brain slice cultures.
Result
Lymphocytes do not induce cell death in slice cultures in the absence of any toxic
insult whereas, after applying toxic insult to the slice cultures using kainic acid,
lymphocytes show neuroprotection against such insult. Similarly, purified non-
activated and purified activated T cells along with T cells depleted lymphocyte
preparation also exhibit neuroprotection against kainic acid-induced cell death.
We further, have demonstrated that the observed neuroprotection is contact-
independent and soluble mediators released from lymphocytes are responsible
for the observed neuroprotection. Moreover, our study has revealed that soluble
mediators exhibiting neuroprotection act via astrocytes.
Conclusion
Lymphocyte preparations are neuroprotective and the observed neuroprotection
is contact-independent. Soluble mediators released from lymphocytes are
responsible for the observed neuroprotection.
KEY WORDS
Astrocytes, lymphocytes, neurodegeneration, neuroprotection, t cells
Description
Shrestha R,1,4 Millington O,2 Brewer J,1 Bushell T3
1Centre for Neuroscience
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
2Centre of Biophotonics
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
3Institute of Infection, Immunity and Inflammation
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
4 Department of Pharmacology
Dhulikhel Hospital - Kathmandu University Hospital Kathmandu University School of Medical Sciences Dhulikhel, Nepal