Elevated Levels of Neuron-Produced Cytokine Protect Against Parkinson's Disease

A cytokine produced by neurons has been found to block the inflammatory activity - which has been linked to neurodegenerative disorders such as Parkinson's disease - of other brain cells known as microglia.

Microglia, which constitute 20% of the total glial cell population within the brain, function as the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS). Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via substances produced by the neurons. Chemokine (C-X3-C motif) ligand 1 (CX3CL1) is a large cytokine protein of 373 amino acids produced by neurons that suppresses the activation of microglia. It is also commonly known under the names fractalkine (in humans) and neurotactin (in mice).

In the current study, investigators at the University of South Florida (Tampa, USA) used a rat Parkinson's disease model to determine if the CX3CL1 pathway could be a therapeutic target to prevent excessive microglia activation that contributes to neurodegenerative disease. To this end, a group of these animals was treated for 28 days with recombinant CX3CL1, which was delivered to the striatum by an osmotic minipump.

They reported in the January 25, 2011, online edition of the Journal of Neuroinflammation that CX3CL1 was able to suppress microglia activation. The reduced microglia activation was found to be neuroprotective, as the CX3CL1 treated rats had a smaller lesion volume in the striatum and, importantly, significantly fewer lost neurons.

"In the brain, one aspect of immune regulation occurs through neurons,” said senior author Dr. Paula C. Bickford, professor of neurosurgery at the University of South Florida. "Immune cells called microglia can damage neurons by producing bioactive molecules. On the other hand, a neuron-generated signaling chemical, or fractalkine, also called CX3CL1, suppresses the activation of microglia. Our study examined whether adding CX3CL1 beyond normal levels could decrease microglial activation and, therefore, play a neuroprotective role by helping prevent the loss of important neural cells in an animal model of Parkinson's disease.”

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