HOUSEKEEPING AND HIGHER FUNCTIONS ARE MARRIED AND INSEPARABLE IN THE BRAIN

Three new papers show that our neurons need housekeeping and support help. These papers lend further support to the “whole-body” view of the brain.  That is, not only is there more to the brain than neurons, but the split between “lofty signaling activities” and “humble housekeeping” is artificial and misleading because all are key team players.  These new papers also support the idea that sensible, health-promoting strategies — particularly a high nutrient-density plant-based diet, may help protect our brains and our general health.

Below, I’ve summarized the three studies and the key questions they raise:

Could psychiatric problems be linked to cell energy problems?

One paper, about brain cell energy in a review called “Impaired mitochondrial function in psychiatric disorders,” shows that brain cell energy function now appears to be a problem for most or all psychiatric illnesses – even though most people with these issues don’t have official gene mutations causing mitochondrial “diseases.”

The mitochondrial paper talks about how enhancing mitochondrial function can be a great target for novel drugs and therapeutics. That’s exciting, but may take a decade or more for drugs to reach patients, which will take billions of dollars worth of clinical trials and risk side effects that may turn many promising starts into dead ends.

Meanwhile mitochondrial dysfunction can also be targeted with food, because our mitochondria are very vulnerable to nutritional deficiencies — and can respond quite well to intensive food interventions such as “mitochondrial cocktail” vitamin combinations or a super-health “food as medicine” diet.

Could the immune system play a key role in developmental disorders?

In the second paper, “Wild-type microglia arrest pathology in a mouse model of Rett syndrome,” the investigators were able to stop and even reverse the symptoms of a serious genetic disorder of development called Rett syndrome. The mice were given healthy microglial cells through a bone-marrow transplant from wild-type mice (that is, normal healthy mice without the Rett genetic mutation) – and then they got better.

This paper is remarkable because it shows that our previous research into Rett syndrome – which primarily addressed dysfunctional neurons – was incomplete.  The mice in this study got better because they got new microglia that functioned better. The microglia they’d started with took a hit from the Rett genetic mutation and weren’t doing their job of “taking out the trash” from the neuronal environment. When the healthy microglia came into the system and started doing their job, the disease stopped getting worse and stayed stable – quite unlike the normal course of the condition.  When the scientists tested this idea by stopping the “garbage collection” role of the microglia, all the gains were lost and the mice got sicker.

Amazingly, nothing was done to the neuron itself in the intervention.  Just the microglia.  This suggests that the symptoms of the disorder might be driven by mischief related to the microglia, not just genetic insults to the neurons, as has been assumed.  Maybe the problem is the garbage created by the chaos and dysfunction from the gene mutations, not just (or even not mainly) the gene mutation’s impact on the neurons.

So is Rett Syndrome really “neuro”developmental? Or does that term mislead us and put blinders on our vision?  Doug Fields, author of THE OTHER BRAIN, a wonderfully readable book on glial cells, suggests as much.

If this is true, is it also possible that conditions like autism, which have also been assumed to be due to neuronal problems, might also be highly shaped by microglial problems? In the case of Rett Syndrome, microglia are messed up for genetic reasons.  In lots of other conditions, including autism, microglia may well be activated for some other reason — perhaps just environmental exposure since many exposures and infections can activate microglia.  This means that addressing environmental issues – improving food and reducing toxic exposures – may help a lot.

Even in Rett syndrome, where there is certainly a genetic problem, isn’t is possible that more toxic environmental exposures and poor nutrition could make things worse – or vice versa – could healthy environmental inputs improve wellbeing in meaningful ways, slowing the disease’s progression and making people with Rett syndrome less uncomfortable?  So often, doctors quite trying to look for ways to help when they find a gene – but even then, perhaps other things can still make life better.

To help microglia cells do better, we may not need to identify a specific molecule to target with a drug.  If we improve health – through taking care of optimizing food, avoiding toxins and infection and minimizing stress – as I lay out in my book The Autism Revolution: Whole Body Strategies for Making Life All It Can Be  – microglial cells won’t have to work so hard fighting off dangers and may be more effective at everyday housekeeping.

Though we haven’t yet confirmed the microglia hypothesis, and might not for years, doesn’t it make sense to start testing now to see if the activities we know will improve microglial function will also improve conditions like Rett Syndrome and autism?  For some of those whose conditions are more environmental than genetic, this might make a major difference.

Coda: The typical American diet couldn’t be worse for microglia, promoting inflammation that spurs microglia to get “activated” and spew out all sorts of chemicals that irritate and overexcite the brain.  Maybe the lessons we learn from autism and Rett could help all people function better.

Are neurons necessary to cause “neurological” disease?  

The third paper, called “Astrocytes conspire with neurons during progression of neurological disease,” shows that astrocytes (or astroglia – which are glial cells alongside  microglia), also previously thought of as “housekeeping” cells, can start or worsen many neurological diseases.

We now know that astrocytes and neurons conspire, but which comes first? We don’t know.  The paper contains a table asking whether neurons are necessary or sufficient to cause various diseases – and the same for astrocytes. Could a problem that starts with astrocytes cause “neuro”logical disease?  Good question.

What do these papers have in common?

In all three papers, so-called “housekeeping” issues cause major problems for the “lofty” neurons.

In the mitochondrial paper, the impaired energy system gets in the way of how neurons can function.

In the microglia paper, the microglial cells impact how neuronal signaling occurs by failing to clean up a lot of the debris due to a genetic impairment.

In the astrocyte paper, astrocytes are shown to play an important role in brain diseases.

What all of these papers have in common is that they elevate housekeeping functions from mundane background activities to pivotal players in the highest activities of the brain.   The energy supply functions of the mitochondria and the cleanup functions of the microglia can no longer be assumed to be unimportant  to lofty brain functions like language and creativity.

Good news: personal and scientific

There are two kinds of good news from these papers.  The first is that there are things we can do right now that can help the situation a lot.   And food can play a central role. By eating a healthy, anti-inflammatory diet, we can help our microglia and astroglia more consistently take out the trash, support energy production and keep neurons in good shape – and keep them from being distracted by having to be constantly fighting battles.

The second is that neurons are not soloists but parts in an orchestra.  Other instruments in the orchestra include glial cells like microglia, and physical parts of the brain – like blood vessels – which get open or constrict to help regulate how strongly signals are sent around.  Unlike neurons, which don’t reproduce much, our brains can make lots of new glial cells and sprout new blood  vessels – both of which can help the whole brain to work better, and which are much easier to influence through diet and everyday activities than are neurons. Scientists studying this orchestra need to start looking past the violin section.

Brain housekeeping and higher functions in autism and beyond

We need a “higher synthesis” of housekeeping and higher cortical functions in the way we study the brain. This might lead to understanding how much more we can do right now to prevent brain dysfunction and help those already suffering from it.

While we wait for that higher synthesis you have nothing to lose by optimizing your diet. As I said above, an anti-inflammation diet (like plant-based, low starch, free of processed food, unprocessed meats (preferably grass-fed), health fats and lots of different colored fruits and vegetables) is an excellent foundation for reducing inflammation and even restoring health.  It will be great for your brain – and the rest of your body too – for you, your family and the health and good brain function of everyone.