Neuroinflammation – inflammation of the brain and spinal cord – is a major driver in a broad spectrum of neurological disorders, from acute syndromes like stroke and head injury to chronic neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
Non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of drug therapy against inflammatory conditions from arthritis to headaches to back pain. And there are indications that daily use of some NSAIDs (for instance aspirin) may fend off conditions of neuroinflammatory origin such as Alzheimer’s and Parkinson’s.
There’s also good evidence that much of neuroinflammation’s sting can be traced to barbs called microglia – a collective term denoting the brain’s very own set of immune cells. As first-rate scientists including Ben Barres, MD, PhD, and others have written, malfunctioning microglia may underlie much of what goes wrong in the arc of neurodeneration.
A new study by Stanford neuroscientist Kati Andreasson, MD, suggests that putting the chill on neuroinflammation by shutting down a particular protein on the surface of microglial cells may be beneficial.
In a 2011 release describing earlier work along these lines by Andreasson, I wrote:
NSAIDs block both COX-2 and COX-1, two very similar versions of cyclo-oxygenase, an enzyme that catalyzes a key chemical reaction in the production of five related hormone-like messenger molecules called prostaglandins… Prostaglandins travel from one cell to another, landing on… dedicated receptor molecules sitting on cells’ surfaces and stimulating various activities inside those cells. Each type of prostaglandin can trigger distinct effects. One prostaglandin in particular, PGE2, is known to be associated with pain and inflammation. PGE2 has four separate counterpart receptors, designated EP1 through EP4, each of which sets in motion a different set of activities inside cells on binding to PGE2.
In the new study, which appears in the Journal of Neuroscience, Andreasson and her colleagues (including fellow Stanford neuroscientist Marion Buckwalter, MD, PhD,) specifically blocked PGE2’s function in mice’s microglia. Doing this reduced brain inflammation in the presence of toxins that are known to be highly neuroinflammatory – including one called MPTP, a substance that has caused Parkinson’s disease among young drug users. Importantly, nerve cells located in the substantia nigra, a tract whose demise is a central feature of Parkinson’s disease, suffered much less damage in the presence of MPTP among mice whose microglia were missing PGE2.
“NSAIDs have a number of adverse effects, because blocking the COX enzymes blocks not only toxic prostaglandin actions but beneficial ones as well,” Andreasson told me. “If we can put our finger on prostaglandins’ toxic downstream effects, such as the microglial effect examined in this paper, we should be able to generate safer, stronger therapies in neurological disease, and other diseases as well.”
Previously: Untangling the inflammation/Alzheimer’s connection, When brain’s trash collectors fall down on the job, neurodegeneration risk picks up, Malfunctioning microglia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and Neuroinflammation, microglia and brain health in the balance
Photo by wilbanks