Yes interesting.
One thing that interested me was leptin testing as a possible biomarker. We are starting to get a good collection of tests that could be used as a diagnosis.
leptin issues could be a sign of mitochondrial dysfunction? ?
I believe leptin is not found to be high, but rather correlates with fatigue. He (Dr Younger) says that the microglia are sensitized (mentions bacteria, virus, diesel particles as possibilities) and I presume therefore normal leptin levels exaggerate the response by the microglia. That's my take on it. Although, confusingly, later in the talk he does say leptin sensitizes microglia. Here are my very rough notes on Dr Youngers talk:
- theory: could be a parameter that is not above a threshold but still driving symptoms: that could happen if , eg, the downstream targets of that cytokine or parameter are sensitized (it’s threshold has been suppressed)
- 3 women with fibro
o Measured many metabolites
o Lots of things correlated with sx but only thing correlated in all 3 sx – leptin
- 10 women with CFS
o Hypothesized leptin would correlated with fatigue
o 6 out of 10 patients correlated significantly
- 10 healthy women who had fatigue
o Almost never a correlateion between leptin and fatigue
o 1 person showed a correlation
- Did network analysis b/c so far only looked at leptin
o Leptin is only cytokine correlated with fatigue
o Leptin is correlated with a lot of other cytokines and chemokines
o Those analytes may be driving the leptin which is the final gateway driving the fatigue
- If we only know cytokines can we predict if you are having a good day or bad day ?
o 78.3% accuracy in predicting whether you are having a good or bad day on new data
o 55.15% in controls (no better than chance)
o This means these cytokines have to be related to fatigue in a meaningful way
o These are inflammatory based markers so we really have to look carefully at inflammation in CFS
- Leptin
o 3 times higher in women than men
o Extremely inflammatory
o Can change immune system drastically
- Microglia
o Immune system cells in our brain and spinal cord
o Our primary defence in the brain and spinal cord
o Patrol and look for problems – viral , bacteria, cell death and when they find a problem they change shape drastically and pump out proinflammatory factors in your brain and spinal cord
o These factors interact with neurons and lower the threshold of those neurons to fire, particularly neurons that communicate something bad is happening – neurons responsible for the experience of pain and neurons responsible for the experience of fatigue
- Coughing and runny nose engaged by different mechanism than microglia
- What is supposed to happen when you get sick, is microglia activate, you get rid of the infection and you feel better
o What if you had a condition where the microglia became sensitized and overexpressed the receptors that we’re looking for probblems
o What if they were primed and can be activated on a hair trigger ?
§ It turns out microglia can be primed – they can be pushed into this hypersensitive state – called primed
§ When primed it takes very little stimulus to push them into active mode
§ A lot of things can prime microglia – aging, chronic stress, exposure to diesel particles, opiod medications over time, a huge immune hit, multiple immune hits
- Leptin crosses the BBB and sensitizes microglia
- Il-1 is strong indication of microglia activation
- Leptin does 2 things to microglia : lowers their threshold and it makes them react much more than they should once they are activated
- Potential role of leptin in causing ME symptoms
- The whole model
o Microglia are sensitized – could be due to any number of reasons – viral, bacterial, post lyme etc
o Then they are sensitized and start to react to something like endogenous opiods
o Then they are chronically activated so the minor amount of exertion and the chemicals that are produced from that can now set off alarm bells that should only be set off if you’re really sick
o Says leptin plays into this but doesn’t explain how
- Treatment
o Leptin antagonists
o Doesn’t recommend attacking leptin directly b/c leptin interacts with every kind of immune cell you have
o Caloric restriction, avoiding stress eating, eating low GI diet reduce leptin
o Instead of targeting leptin, can target primed microglia directly
§ List includes naltrexone; all reduce microglia excitability
§ Also list of herbs etc – includes pycnogeol, boswella etc
- Leptin microglia is one of the subtypes