Microglia in the aging brain: relevance to neurodegeneration
Xiao-Guang Luo , Jian-Qing Ding and Sheng-Di Chen

Molecular Neurodegeneration 2010, 5:12doi:10.1186/1750-1326-5-12


Published: 24 March 2010

Abstract (provisional)
Microglia cells are the brain counterpart of macrophages and function as the first defense in the brain. Although they are neuroprotective in the young brain, microglia cells may be primed to react abnormally to stimuli in the aged brain and to become neurotoxic and destructive during neurodegeneration. Aging-induced immune senescence occurs in the brain as age-associated microglia senescence, which renders microglia to function abnormally and may eventually promote neurodegeneration. Microglia senescence is manifested by both morphological changes and alterations in immunophenotypic expression and inflammatory profile. These changes are likely caused by microinvironmental factors, but intrinsic factors cannot yet be completely excluded. Microglia senescence appears to underlie the switching of microglia from neuroprotective in the young brain to neurotoxic in the aged brain. The hypothesis of microglia senescence during aging offers a novel perspective on their roles in aging-related neurodegeneration. In Parkinson's disease and Alzheimer's disease, over-activation of microglia may play an active role in the pathogenesis because microglia senescence primes them to be neurotoxic during the development of the diseases.


http://www.molecularneurodegeneratio.../1/12/abstract

http://www.molecularneurodegeneratio...-1326-5-12.pdf

access to full text of the article.

http://www.pdonlineresearch.org/resp...lpha-synuclein

Microglia and alpha-synuclein
By Carolina Cebrian, PhD, Postdoctoral Research Scientist, Columbia University
(SNCA/Alpha-Synuclein), Neuroimmune Function


Their data indicate that alpha-synuclein expression not only leads to persistent microglia activation, but that depending on the degree of induced neuropathology distinct microglial responses will occur. They describe the existence of two distinct microglial responses dependent on the stage of alpha-synuclein induced neuropathology: alpha-synuclein expression levels capable of inducing dopaminergic cell death correlate with the long-term induction of macrophagic microglia; however, at levels where only neurodegeneration is taking place, they just observe microglia with antigen presenting capabilities. This work brings to light better understanding on the cellular events that could take place in the brain during the chronic development of PD.

Thanks all for sharing this explanatory information; I had wondered for quite some time how the microglia, macrophage, and alpha-synuclein all interrelate in the PD environment.

One thing that I have never understood is how everything seems to be chalked up to "aging", so does this mean when an 18 year old young man is diagnosed with PD that this cellular dynamic is occurring in him already; most probably the microglia with antigen, does this mean that he in essence has the brain profile of an 80 year old? In other words, let's pretend we can observe his brain pathology without knowing anything about him other than he seems to have PD, would doctors then guess his age to be much older base on the cell death?

I guess I have a hard time understanding how a 20 or 30 year old can have what looks like a senescent brain. Are we saying that the PD process of neurodegeneration prematurely "ages" the brain? Or might a Young Onset person present with symptoms because his brain has already taken on what is normally a process of aging- the "aged" environment was already there and it results in what looks like PD?

Wow, that is clear as mud. lol If anyone can suss out what I am asking and respond, that would be great!

Laura

Laura-
Regarding microglia, first think of the problem as an neuroinflammatory process that has multiple possible origins. Among the things that can trigger it are prenatal maternal infections and general aging, the two ends of a spectrum. There are other triggers in between, too. A case of influenza at mid-life for example. The common element is activation of the microglia. In a sense, just what triggered it is immaterial.

Once triggered, the process can be affected by "factors" such as genetics, chemicals, stress, etc. It is the complex interplay between causes, triggers, and factors that make PD a maddening designer disorder.

Age is a big factor. Older microglia are more excitable than younger, so it is relatively common for a, say, 70-year old system to be triggered. Similarly, a newborn exposed to bacterial toxins in the womb, may *after the chemistry changes of puberty* experience a near spontaneous activation that, 20 years later, makes itself known.

Again, the most important thing to understand is that there are multiple causes that set the stage, triggers that raise the curtain, and factors such as the critics in the next day's paper that influence the course of the drama.

August 7th, 2009

New discovery may explain premature ageing

http://www.thaindian.com/newsportal/...#ixzz0jVEnKXbG

this includes pd in the possibilities

another interesting article

http://www.thaindian.com/newsportal/...100329740.html