Saturday, November 21, 2015

Brain Inflammation in Dementia with Lewy Bodies

Bill Yates
Brain Posts
Nov 10 / 2015

The role of inflammation in the brain is receiving increased attention in dementia and other disorders in neuroscience medicine.

Dementia with Lewy bodies (DLB) is the third leading cause of dementia. This disorder has received increased attention with the finding of the condition in the autopsy of comedian and actor Robin Williams.

Patrick Ejlerskov and colleagues from Denmark, Sweden, Germany and the United Kingdom recently published an informative study in the journal Cell on this topic.

Cytokines include a group of substances that modulate immune and inflammation. Included in this group of substances are interferon, interleukin and various growth factors. Many cytokines promote inflammation in response to a variety of triggers. However, some interferon compounds, including interferon beta appear to dampen or reduce the inflammatory response. A lack of interferon beta may allow excessive unopposed pro-inflammatory responses.

In the current study, the role of interferon beta in brain inflammation was studies in a model model. The key findings from this manuscript included:
  • Mice with no interferon beta (using a knockout model) showed evidence of behavioral and cognitive impairment along with signs of brain neurodegeneration
  • Interferon beta was essential for neuroplasticity markers including neuronal survival, neurite outgrowth and branching
  • Interferon beta knockout mice showed disruption of pathways associated with neurodegeneration
  • Low interferon beta levels demonstrated defects in the dopamine pathway in the brain nigrostriatum. This pathway is known to be disrupted in Parkinson's disease (PD).
  • Lack of signaling of the interferon beta pathway produces brain Lewy bodies
  • Lack of interferon beta disrupts the brain cleansing process known as autophagy
  • Disruption of autophagy results in the accumulation of the Lewy body-associated protein known as alpha synuclein
  • Mouse gene therapy with the interferon beta gene prevented dopamine neuron loss in a familial model of PD
This study presents a pretty impressive argument for the role of interferon beta in the modulation of brain neuroinflammation pathways found in DLB and Parkinson's disease.

The authors conclude in the discussion section:
"Our data strongly support an essential role for interferon beta signaling in the preventing neurodegenerative pathology and suggest (interferon beta knockout) mice as a model for nonfamilial, sporadic neurodegenerative diseases, particularly PD and DLB, with potential for testing future therapies."
Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.

Photo of Lewy bodies under the microscope is from Wikipedia and is used under the terms of the Creative Common License linked to the following citation:
"Lewy Koerperchen" by Dr. Andreas Becker upload here Penarc - Own work. Licensed under CC BY-SA 3.0 via Commons.


Follow the author on Twitter @WRY999.

Ejlerskov P, Hultberg JG, Wang J, Carlsson R, Ambjørn M, Kuss M, Liu Y, Porcu G, Kolkova K, Friis Rundsten C, Ruscher K, Pakkenberg B, Goldmann T, Loreth D, Prinz M, Rubinsztein DC, & Issazadeh-Navikas S (2015). Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia. Cell, 163 (2), 324-39 PMID: 26451483.



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