Remember when you were a kid? Happy and carefree?
“Why am I not like that now? Is that forever out of reach?”
When I struggled with depression, I wondered about that myself and did some research (linked references are at the end).
To put it in a nutshell:
We must ensure the specialized crew in our brain has all the resources they need to keep things in balance. This involves good sleep habits, quality nutrition, and exercise.
Sometimes things happen in life that makes a good mood more challenging, but not impossible.
What is Causing The Depression?
There are factors that may affect us. For example, if you have diabetes or have experienced head trauma, you are at a much higher risk for problems with thinking and memory because the brain’s plumbing system isn’t working right. (1). The cause is similar to Major Depressive Disorder (2).
The brain’s plumbing is technically known as the glymphatic system. It is responsible for intake and output and is mainly active at night (3).
We need to expand our metaphor to a broader illustration to avoid oversimplification.
The City of Your Body
Neighborhood Body Cells
The body has a circulatory system that works in conjunction with the lymphatic system. Think of it like a city: each house has incoming water, electric, gas, and outgoing sewage drainage lines. They also have people bringing in supplies and taking out the garbage.
Our cells are like houses, each with incoming pipes bringing in nutrients (electricity), oxygen (gas), and water. Waste products (garbage, sewage) are taken out through the lymphatic system (sewage drainage lines) and are connected by endothelial cells (like pumping stations).
Government Brain Cells
The brain is more integrated, like the offices and cubicles of a government building staffed by personnel, computers, phones, internet lines, etc. Secret Service agents are responsible for ensuring security.
Imagine if government office workers were inept at handling things professionally (a bit like children). What if no one played referee?
What if nobody ensured the garbage was emptied or things were clean? Nobody would get anything done.
Everything and everyone must be kept safe and super clean physically and emotionally.
This would require something like superhero office moms, each working as a psychologist, emergency responders, communication specialists, ninjas, etc.
A somewhat incomplete job description goes like this:
Maintain high morale
Ensure peaceful relations
Use tourniquets, splints, defibrillators
Repair broken relationships
Defend against derelicts
Supervise all communications
Coordinate waste removal
Maintain well being
Without them, your brain would be in quite a jam. Who are they? Meet the astrocytes.
Superhero Office Mom Astrocytes
Astrocytes play a variety of roles (6). It is much more fun to use the family metaphor than office politics, so here we go:
- Regulating homeostasis (2): ”get a move on, we’re running late” or “everybody just chill, please”
- Monitor neurotransmitter production for efficient communication between neurons (2,6): “junior, tell her you’re sorry” and “hey, stop smacking your brother”
- Distribution of glucose, lipids, amino acids, growth factors, and hormones (3): “yes dear, I ordered that last week, but it’s not arrived yet”
- Controlling inflammation (2): “yes, you have a temperature; you better stay home”
- Coordinating with microglia for security (3,4,6): “yes officer, that creep is up our street again… if he comes in here, I’ll eat him for breakfast”
- Sectioning off areas under repair (6): “junior, for the umpteenth time the upstairs is locked for a remodel”
- Clearing ROS and cytokines from interstitial fluid (2,3,5): “honey, the toilet is plugged again, and you forgot to take the garbage out”
These will be removed from the cerebrospinal fluid (the sewer lines and dumpsters) and finally to the meningeal lymphatic vessels to be removed from the brain (garbage trucks taking to the landfill), which usually occurs during sleep (3).
Now imagine billions of moms, dads, and children. At night, while the children are sleeping, things need to be cleaned up before the mayhem begins the following day anew. Without making the best of the resources needed to keep things stable, things could get messy really quickly. What do I mean?
What Could Increased Glutathione Levels Make Possible?
Making the best of resources means increasing the antioxidant capacity, not just the amount, which involves raising glutathione.
Raising glutathione will:
- improve sleep
- reduce inflammation
- recharge antioxidants
- reduce the production of reactive oxygen species (ROS)
This could, in turn:
- reduce DNA, protein, and lipid damage
- modulate neurotransmitter release and monoamine oxidase activity
- reduce excess neurotransmitters like dopamine, serotonin, and norepinephrine (2,3)
- reduce excess neural activity through the parallel activation of both neuronal mitochondria and astrocytic clearance (2)
How Could Glutathione Make You Feel?
- Less nerve, joint, and chronic pain
- Make antioxidants and nutrients in food and supplements work better
- Feel better more often
- Respond to stress more appropriately
- Bounce back faster after infections
- More energy throughout the day
- Improved sleep
- Better skin
Clearly, raising glutathione would really be helpful. What would it take to do that effectively? I’d be happy to help.
Citations
- Jiang Q, Zhang L, Ding G, et al. Impairment of the glymphatic system after diabetes. J Cereb Blood Flow Metab. 2017;37(4):1326-1337. https://doi.org/10.1177/0271678X16654702. Accessed February 25, 2023.
- Gu S, Li Y, Jiang Y, Huang JH, Wang F. Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders. Antioxidants (Basel). 2022;11(11):2296. Published 2022 Nov 20. https://doi.org/10.3390/antiox11112296. Accessed February 25, 2023.
- Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner's Guide. Neurochem Res. 2015;40(12):2583-2599. https://doi.org/10.1007/s11064-015-1581-6. Accessed February 26th, 2023.
- Brandi E, Torres-Garcia L, Svanbergsson A, et al. Brain region-specific microglial and astrocytic activation in response to systemic lipopolysaccharides exposure. Front Aging Neurosci. 2022;14:910988. Published 2022 Aug 26. https://doi.org/10.3389/fnagi.2022.910988. Accessed February 26, 2026.
- Benveniste H, Lee H, Volkow ND. The Glymphatic Pathway: Waste Removal from the CNS via Cerebrospinal Fluid Transport. Neuroscientist. 2017;23(5):454-465. https://doi.org/10.1177/1073858417691030. Accessed February 26, 2026.
- Chiareli RA, Carvalho GA, Marques BL, et al. The Role of Astrocytes in the Neurorepair Process. Front Cell Dev Biol. 2021;9:665795. Published 2021 May 25. https://doi.org/10.3389/fcell.2021.665795. Accessed February 26, 2026.