Autism, SHANK, and busy highways

Two autism studies in the news. I’ve summarized them at the Thinking Person’s Guide to Autism here. Let’s just say that the headlines, stories, and news releases have hyped yet again. Indeed, the title of this post should’ve been: “Headlines hype, news releases overpromise again in autism research.”

The worst offender is easily, “Proximity to freeways increases autism risk, study finds.” Um, no. The study found that autism rates are higher among people living within 309 meters of freeways. That in no way means that living close to a freeway increases autism risk. It’s a common, basic overinterpretation of correlation and epidemiological conclusions, but it’s really starting to get old. You can read more about the fuzzy definition of “freeway” and “major road” here.

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Think the eye defies evolutionary theory? Think again

The compound lens of the insect eye

Win for Darwin

When Darwin proposed his theory of evolution by natural selection, he recognized at the time that the eye might be a problem. In fact, he even said it was “absurd” to think that the complex human eye could have evolved as a result of random mutations and natural selection. Although evolution remains a fact, and natural selection remains a theory, the human eye now has some solid evolutionary precedence. A group of scientists that has established a primitive marine worm, Platynereis dumerilii, as a developmental biology model has found that it provides the key to the evolution of the human—and insect—eye.

Multiple events in eye evolution, or only one?

The divide over the eye occurred because the insects have the familiar compound-lens—think how fly eyesight is depicted—and vertebrates have a single lens. Additionally, insects use rhabdomeric photoreceptors, and vertebrates have a type known as ciliary receptors. The rhabdomeric receptors increase surface area in the manner of our small intestine—by having finger-like extensions of the cell. The ciliary cells have a hairy appearance because of cilia that pop outward from the cell. A burning question in evolutionary biology was how these two very different kinds of eyes with different types of photoreceptors evolved. Were there multiple events of eye evolution, or just one?

Just once?

P. dumerilii work indicates a single evolutionary event, although the usual scientific caveats in the absence of an eyewitness still apply. This little polychaete worm, a living fossil, hasn’t changed in about 600 million years, and part of its prototypical insect brain responds to light. In this system is a complex of cells that forms three pairs of eyes and has two types of photoreceptor cells. Yep, those two types are the ciliary and the rhabdomeric. This little marine worm has both kinds of receptors, using the rhabdomeric receptors in its little eyes and the ciliary receptors in its brain. Researchers speculate that the light receptors in the brain serve to regulate the animal’s circadian rhythm.

How could the existence of these two types of receptors simultaneously lead to the evolution of two very different kinds of eyes? An ancestral form could have had duplicate copies of one or both genes present. Ultimately, if the second copy of the rhabdomeric receptor gene were recruited to an eye-like structure, evolution continued down the insect path. But, if the second copy of a ciliary cell’s photoreceiving gene were co-opted for another function, and the cells were ultimately recruited from the brain for use in the eye, then evolution marched in the vertebrate direction.

All of the above is completely speculation, although this worm’s light-sensitive molecule, or opsin, is very much like the opsin our own rods and cones make, and the molecular biology strongly indicates a relationship. It doesn’t completely rule out multiple eye-evolution events, but it certainly provides some nice evidence for a common eye ancestor for insects and vertebrates.

Note: This work appeared in 2004 and got a detailed writeup at Pharyngula.

Bisphenol A: multisystem effects

These bottles were produced without BPA in response to concerns about the chemical. Photo via Creative Commons, attributed to Alicia Vorhees, thesoftlanding

Are endocrine disruptors stealing our future?

Endocrine-disrupting compounds are chemicals in the environment—usually compounds that we have introduced—that can alter normal hormone signaling processes. Often, exposure to these compounds has little immediate effect in adult animals, but it can have big effects on organisms during sensitive developmental periods, like embryogenesis. During embryonic development in vertebrates, steroid hormones govern many processes, and the fetal hormone environment is usually carefully calibrated to ensure that these processes go forward normally.

Tiny amounts, big changes

But many compounds disrupt these processes, knocking them off track and resulting in development that is unusual or abnormal. For example, male alligators exposed in the egg to these compounds—which often persist in fatty tissues or yolk—emerge with serious penile abnormalities that can affect their ability to reproduce. The banned pesticide DDT is probably one of the best-known of these compounds, and exposure to it or its metabolites has been shown to disrupt hormone signaling to the point of altering sex development completely.

When we think of hormones, we often think of puberty, the time when hormones seem to govern our every move. When we think of estrogen, we probably think “female” because estrogen has historically been considered the “female” hormone. What you might not know is that estrogen, which is made in the ovaries, is also made in our brains during embryonic development. In mammals, appropriate male development appears to require neural estrogen synthesis. When estrogen synthesis in embryonic mammals is blocked, the males that develop do not exhibit typical male behaviors when they reach reproductive maturity.

Bisphenol A: ubiquitous chemical

Among the compounds that have been identified as endocrine disruptors is bisphenol A (BPA). In the United States, we produce about 2 billion pounds of BPA a year. Previous studies have demonstrated that BPA can disrupt thyroid signaling to the point of affecting the thyroid’s role in appropriate brain development. In addition, BPA has been linked to feminization of reptiles. Some scientists were aware of BPA’s hormone-activity potential as far back as the early twentieth century.

But because no one took that knowledge or its potential seriously—the field of endocrine disruptors is relatively young—BPA has found its way into almost every aspect of our lives. It is in the dental sealants we put on our teeth to keep the cavities at bay. It is in the lining that coats the insides of food cans to keep the metal from rusting. It is in the hard plastic that we use for baby bottles and teething rings. And it can leach from these products into the food that we eat. BPA is found at high levels in some pregnant women, and it appears to accumulate in higher concentrations around the umbilical cord and in the fetal amniotic fluid.

BPA and effects on the developing brain

Work from Yale and from researchers in Japan also points to some potentially serious effects on the brain. Part of the role of estrogen in brain development is facilitating synaptic connections in a crucial brain area called the hippocampus. The hippocampus is the center where neurons organize that will later be activated to produce sex-appropriate activity in vertebrates. It is also the area of the brain involved in the formation and retention of memory.

The researchers found that small doses of BPA—doses that fall within EPA-approved levels for exposure—can inhibit hippocampal synaptic formation in rats, counteracting the effect of estrogen. That BPA is an estrogen inhibitor could be serious for our brains if the results translate into human effects. As we age and our endogenous estrogen levels decrease, for example, the hippocampus suffers and our memory does, too. If BPA sets this process in motion even earlier, hippocampal—and thus, memory—decline may occur even earlier.

Rodents, monkeys, and people–oh, my

A recent report in Environmental Health Perspectives concludes that rodents, rhesus monkeys, and people all exhibit similar pharmacokinetics with BPA and that exposures may be far greater than previously calculated. Other recent studies suggest effects on sugar metabolism related to diabetes, an association with polycystic ovarian syndrome in rats, and a relationship to the development of asthma in a mouse model.

Leeches model reproductive behavior

No, not that kind of modeling.

Leeches have a bad reputation because they dine on blood. Even forgetting for the moment such human-designed culinary delicacies as blood pudding or blood sausage, let’s just say that sucking blood does not necessarily an incubus make.

Not just blood-sucking boneless terrors

In fact, leeches have recently made a comeback in the shape–the slimy, creepy shape–of their use as medical therapy. Their former role was to suck bad humors from the body. Today, with our improved understanding of molecular biology and relegation of humor to Jon Stewart, leeches serve a different purpose. Pracititioners encountering venous insufficiency and premature clotting during certain surgeries can apply leeches–and their salivary anti-clotting factors–locally to address the problem. By the way, the medicinal use of leeches–which has a history stretching back for milliennia–is called hirudotherapy.

Model leeches

And leeches also make an oxytocin-related hormone called hirudotocin that plays a role in their reproductive behavior. A reproductively aroused leech, it seems, undergoes a maneuver that involves a sloooow, five-minute rotation of its body. The rotation results in alignment of reproductive pores with complementary pores on a presumably adjacent partner.

Animal behavior results, at its core, from an interaction of hormones and the nervous system. But linking the two directly and assessing the influence of hormones on nerves has proved elusive in more complex animals. Leeches, though, have a nervous system more basic than a mosquito’s. And an injection of hirudotocin yields leech reproductive rotation within minutes, accompanied by a leechy mouthing of the potential reproductive partner. In the world of animal behavior research, this is exciting stuff.

Sliced leech anyone?

To track the effects of this hormone through the animal’s nervous system, researchers at Caltech and UCSD examined nervous response to hirudotocin in slices of leech. Then, they did the ultimate direct assessment, removing all of the leech except the nervous system. This approach allowed them to trace directly the activation of the nervous sytem that led to the corkscrewing muscle movements of leech reproductive behavior.

Their next step will be to use voltage-sensitive dyes to detect electrical nerve signals along these paths to see which ones are involved in maintaining the behavior. They may not be drawing out bad humors any more, but leeches are certainly doing their part in helping us tease out the links between hormones and behavior.

For your consideration

Why is it so difficult to link a hormone and a behavior, especially in vertebrates?

This article says that animal behavior is a manifestation of the interaction of hormones and the nervous system. Can you think of some other examples of this interaction?

Animals are not the only organisms that use hormones. Plants do, too, but they lack a nervous system. Identify some plant hormones and determine what plant systems they influence.

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