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Sunlight And the Brain

One of the impressive things about biochemistry and cell biology is how it can produce physical correlates to things that we know and experience, but have no detailed explanation for. There’s a really interesting example out in Cell that has to do with the effects of sunlight on mood and learning. Those effects are real, but no one has understood quite how. Sunlight (generally speaking, its ultraviolet component) is well-known to be used by the body in vitamin D synthesis, and its other effects on the skin are very well known, both bad (sunburn, various forms of skin cancer) and good (relief from psoriasis and several other conditions). Those all make sense, and you can come up with reasonable hypotheses involving inflammation, damage/repair mechanisms, and so on. But how do you get CNS effects?

There was a report in 2014 from an MGH/Harvard team that UV exposure increases beta-endorphin levels in the skin, and that group showed that rodents can apparently become addicted to sunbathing through this effect. The authors of this new paper (a multicenter team from China) may have found another connection. Among other changes, exposure to UV light increases urocanic acid (UCA) in the blood, an effect that’s been known for many years. That’s a metabolite of histidine, and it’s known to be converted on to glutamic acid by the actions of urocanase enzyme. It’s probably coming from filaggrin, an important protein in the epidermis that’s notably high in histidine, but no one’s been sure what (if any) significance this has. The authors, though, have developed a new technique, a sort of patch-clamp mass spec assay, that can detect molecular species at the surface of an individual neuron, and that’s just the sort of thing you’d need to start making connections on a story like this.

What they find is that (1) urocanic acid itself is found in the brain (where it had never been reported). It’s in the CSF, and was detected at neurons in all the brain regions they studied (except the nucleus accumbens, which is known to be a bit different in its permeability to small molecules). Its association with UV exposure indicates that it crosses the blood-brain barrier, and that idea was confirmed by injecting UCA into the periphery and watching its concentration in neurons go up in the same manner. And once in the brain, it’s converted to glutamate (which is, of course, a well-known neurotransmitter). All the enzymes needed for the pathway are present in brain tissue, and the increase in glutamate seen on UCA exposure can be cancelled out by adding a urocanase inhibitor beforehand. (Interestingly, there are real, but smaller, effects on glutamate concentration seen in non-UV exposed experiments, suggesting that the UCA pathway is one of the sources of glutamate in the brain in general). The same effect on glutamate concentrations is seen with shRNA experiments, among others, and the team hit several enzymes in the pathway and saw the expected changes in metabolites each time.

The increased glutamate downstream of UV exposure does indeed set off more brain activity (as shown by electrophysiology experiments), and also shows significant effects on memory and motor-learning activity. Glutaminergic neurons have been implicated in such tasks, so this fits quite well. Overall, the paper seems to do a pretty thorough job of making the connections, and the authors (links added below) conclude that:

Because GLU plays multiple roles in the CNS, including protein biosynthesis at the amino acid level, disposal of excess or waste nitrogen, and signal transduction between neurons as the most abundant excitatory neurotransmitter, the UV-activated intracellular UCA-GLU metabolic pathway in neurons is likely to be involved in sunbathing-related neurological conditions in addition to learning and memory, such as mood improvement, addiction, cognition, and brain development.

We are all aware that the knee bone is connected to the thigh bone, but did you know that the brain was connected to the skin? You’d have to think that beta-endorphin and glutamate are not going to be the end of it (although those two are powerful enough for plenty of effects). One immediately wonders about the well-known effects of sunlight on seasonal depression, among other possibilities. Everything in the body is more or less hooked up to everything else at some level, which is why drug discovery is such a joy sometimes. But finding out these connections, one by one, is the only way we’re ever going to get a handle on disease and health. Another such connection has just been made.



30 comments on “Sunlight And the Brain”

  1. In Vivo Veritas says:

    What, the melanorcortin story was not enough to convince you of a skin-brain link? Actually, a skin-brain-crotch link… 😉

    1. cynical1 says:

      Actually, what he said is spot on. Sunlight……POMC……..alpha MSH and beta endorphin. Sure, I’m guessing the UCA-GLU metabolic pathway is also involved with all these effects at some level but let’s not try to over simplify sunlight and UVB exposure. And maybe someone should look a little harder at those correlations of Vitamin D deficiency to autoimmune and neuropsychiatric disorders and not try to oversimplify that either.

    2. Kevin Rogers says:

      Just look at the effects of melanotan II, it stimulates the melanin receptors. Surprisingly, the highest density of these receptors are in the genital area. Having recreationally used this, I can vouch for it’s near super human capabilities. No handed push-ups, no problem. Pity the poor woman who runs into a guy on this stuff.

    3. In Cervisia Panis says:

      just wondering about people in hospitals… no sunlight in some cases for years!

  2. Uncle Al says:

    It is well denied that pale hair (e.g., blonde) fiberoptic channels sunlight into the brain where a photochemical reaction creates bimbosine. Alas, the effective assay – a candy apple red 1966 Ford Mustang convertible with the top down – is not generally available. Development of vital pharmaceutical behavioral adjuncts is thus denied rioting mobs of screaming harpies.

    1. Nesprin says:

      I know you were trying to be clever, but that was obnoxiously sexist.

      1. ScientistSailor says:

        actually, his post is gender-neutral. Perhaps your bias is showing?

        1. incellulo says:

          Err… I think you will find that dictionary definitions of bimbo and harpy aren’t all that gender neutral.

          1. ScientistSailor says:

            @incellulo The dictionary is a tool of the Patriarchy used to suppress non-traditional gender roles. I, for one, know plenty of males (blond or otherwise) that fit the term “bimbo.” In order to break down gender stereotypes and provide equal opportunity, we must start applying these insults uniformly across genders.

            I’m writing this up for Gender, Place & Culture, who wants to be a co-author?

          2. Uncle Al says:

            Bimbo, bimba. Harpie, harpo. Santa Claus is transgender. Groupthink IQs add like ohms in parallel resistors. Be a Marx generator.

            Medicinal chemistry fails to reliably afford safe and effective product because a whole body of biochemistry must be avoided, plus Accounts Receivable. Otherwise, make a suicide inhibitor then go home.

          3. Zach says:

            There are 3 well known parks in Portland, Oregon where apparently of year’s worth of subjective ethnographic observations should be sufficient to document tens of thousands of blonde-haired humans’ interactions. As long as you document the obvious relationship that we all know to be true (100% of interactions where blonde individuals are labelled as “harpy” or “bimbo” occur where a man applies those terms to a woman), you will no doubt be able to publish in the aforementioned journal. (Please refer to descriptions of Methods and Results of the retracted paper “Dog Park” from the same journal for further information on how to describe your work.)

      2. Dr. Happy says:

        I note that this is a comment on the political palatability of the comment, not on the underlying truth it purports to convey.

        1. tangent says:

          Oh, perhaps I’m not getting it. Care to spell it out?

          1. drocto says:

            Really? This post was the most sense Uncle AI has ever made on this blog.

  3. mlct says:

    I think there’s plenty of evidence that exposure of blue light results in massive cognitive impairment

    1. Chris Phoenix says:

      A quick google seems to show the opposite.

      Maybe you’re referring to blue light at night impairing sleep? Impaired sleep certainly hurts some kinds of cognitive performance.

      1. fajensen says:

        Google would say that, would it not!?

  4. tlp says:

    So nature invented optogenetics before humans

  5. John Wayne says:

    As a comically pale person, I can tell you that I just don’t really enjoy light of any kind. Can any of these biochemically pathways run in reverse? I idea of hell is going to the beach.

    1. Daniel Barkalow says:

      The brain is good at picking up that feeling a certain vague way often leads to several days of pain. It’s easily able to learn that, if a particular collection of biochemical pathways are all doing their generally mood-improving thing, it’s time to seek shade like your life depends on it. These pathways running in reverse would mean that you’d find the beach depressing, not horrific.

  6. Old Pump Kicker says:

    Cue TV commercials for UCA supplements in three…two…one….

  7. babybird says:

    cis urocanic acid is known to be a ht2a agonist.
    whether the paper fererenced identified whether this was cis or trnas in the CNS I don’t know its paywalled.
    so this mechanism doesn’t have to have anything to do with glutamate at all.

    looks like they have a clever toy.

  8. Kaleberg says:

    Does this explain why bright sunny days are so depressing and being out the sun is disorienting? We’ve been having a spate of bright, sunny days and it has been awful. I can hardly wait for the rainy season to pick up. That’s always cheering, and now I might know why.

    1. loupgarous says:

      There’s another explanation, but the research seems to be largely confined to a couple of research sites in Transylvania.

    2. HFM says:

      Is that your reaction to opiates as well? I have comparable reactions to excess sun and opiate pain medications – I don’t get the feel-good effects, I just want to take a nap. (Probably for the best, in both cases.)

  9. Igotmyownlabderrrr... says:

    The tone of this article reminds me of how a lot of the PIs in SoCal thought when I was there for research—pretentious, dumb and uninspired.

  10. dearieme says:

    I enjoy sunny days; I like sitting in the shade looking out at the sunshine. I don’t sunbathe because my skin would peel off. (Established by experiment at about age ten.)

    WhenIwasbutalad we lived with sea to the south. I was a long way into my adult life before I realised how much I’d enjoyed all the reflected light. It made life at 55°N very pleasant.

  11. Fred Flintrock says:

    Snarf grebe frges gnhg

  12. traeh says:

    Lighten up, folks.

  13. Keith Davis says:

    Brain connected to the skin is not as odd as it may seem. Ectoderm, aside from a few other small contributions, forms the nervous system and the epidermis. It makes some sense insofar as one function of the skin is a bedding for a large number of sensory nerves. The relation between some dermatological disorders and stress is also well known.

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