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Role of fractalkine-CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain.

Ali, Idrish LU ; Chugh, Deepti LU and Ekdahl Clementson, Christine LU (2015) In Neurobiology of Disease 74. p.194-203
Abstract
Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status... (More)
Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status epilepticus (SE) was induced in adult rats through stereotaxically implanted electrodes in the hippocampus. Recombinant rat fractalkine or CX3CR1 antibody was infused intraventricularly during one week post-SE. A significant increase in the expression of CX3CR1, but not fractalkine, was observed in the dentate gyrus at one week. CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production. In contrast, fractalkine treatment had only minor effects. This study provides evidence for a role of the fractalkine-CX3CR1 signaling pathway in seizure-induced microglial activation and suggests that neuroblast production following seizures may partly occur as a result of microglial activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
74
pages
194 - 203
publisher
Elsevier
external identifiers
  • pmid:25461978
  • wos:000349655900019
  • scopus:84919816476
ISSN
0969-9961
DOI
10.1016/j.nbd.2014.11.009
language
English
LU publication?
yes
id
3d1a46f6-d357-427c-bb8a-8afe5bbf256e (old id 4912992)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25461978?dopt=Abstract
date added to LUP
2015-01-08 18:19:06
date last changed
2017-10-29 03:06:05
@article{3d1a46f6-d357-427c-bb8a-8afe5bbf256e,
  abstract     = {Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status epilepticus (SE) was induced in adult rats through stereotaxically implanted electrodes in the hippocampus. Recombinant rat fractalkine or CX3CR1 antibody was infused intraventricularly during one week post-SE. A significant increase in the expression of CX3CR1, but not fractalkine, was observed in the dentate gyrus at one week. CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production. In contrast, fractalkine treatment had only minor effects. This study provides evidence for a role of the fractalkine-CX3CR1 signaling pathway in seizure-induced microglial activation and suggests that neuroblast production following seizures may partly occur as a result of microglial activation.},
  author       = {Ali, Idrish and Chugh, Deepti and Ekdahl Clementson, Christine},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {194--203},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Role of fractalkine-CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2014.11.009},
  volume       = {74},
  year         = {2015},
}