Exercise reverses anxiety phenotype in rats

Exercise can ameliorate anxiety and depression-like behaviours induced by an adverse early-life environment by altering the chemical composition in the hippocampus – the part of the brain that regulates stress response, researchers from UNSW have found. [...]

“What’s exciting about this is that we are able to reverse a behavioural deficit that was caused by a traumatic event early in life, simply through exercise,” said Professor of Pharmacology Margaret Morris, who will present the findings this week at the International Congress of Obesity in Stockholm.

In the study, rats were divided into groups and either isolated from their mothers for controlled periods of time to induce stress or given normal maternal contact. Half were given access to a running wheel.

In addition to being more anxious, animals that were subjected to stress early in life had higher levels of stress hormones and fewer steroid receptors in the part of the brain controlling behaviour.

“Both the anxious behaviour and the levels of hormones in these rats were reversed with access to the exercise wheel,” Professor Morris said.

“We know that exercise can elevate mood, but here we are seeing chemical changes that may underpin this improvement. One of these is increases in brain-derived neurotrophic factor (BDNF), which helps nerve cells grow. (via.)

In other news…
Morphine found to decrease testosterone in the brain, as well as liver, and testis. Which is interesting in light of the fact that a stressed/anxious phenotype of rat would have fewer steroid receptors in their brain.

Robert Sapolsky’s 52 minute Lecture on Depression

This is one of the best videos I’ve ever seen on the physiological roots of depression. This guy (Robert Sapolsky) really goes in-depth and connects the dots between scientific facts and common philosophy & anecdote. 52 minutes — not for the faint of heart.

Schizophrenia & immune activation

Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. [...]

Scientists at Karolinska Institutet have now been able to analyse inflammatory substances in the spinal fluid of patients with schizophrenia, instead of, as in previous studies, in the blood. The results show that patients with recent-onset schizophrenia have raised levels of a signal substance called interleukin-1beta, which can be released in the presence of inflammation. In the healthy control patients, this substance was barely measurable. [...]

“We would have made terrific progress if we were one day able to treat schizophrenia patients with immunotherapy, as it might then be possible to interrupt the course of the disease at an early stage of its development,” says Professor Engberg. (via.)

Morphine & brain testosterone levels

A single injection of morphine to fight persistent pain in male rats is able to strongly reduce the hormone testosterone in the brain and plasma [...] The study, led by Anna Maria Aloisi, M.D., showed that opioids had “long lasting genomic effects in body areas which contribute to strong central and peripheral testosterone levels” including the brain, the liver and the testis.

The study showed increases in aromatase, an enzyme that is responsible for a key step in the biosynthesis of estrogen. The findings are particularly important since testosterone is the main substrate of aromatase, which is involved in the formation of estradiol. [...]

Opioid induced hypogonadism can cause health complications to which patients with pain can be overly susceptible, including chronic fatigue, loss of stamina, emotional and sexual disturbances, as well painful skeletal and muscular complications. [...]

“Until a few years ago this condition was completely unrecognized by physicians although some reports clearly showed it in many kinds of patients,” notes Dr. Aloisi. (via.)

This is interesting, because it’s also been demonstrated that chronically anxious rat phenotypes have fewer steroid receptors (testosterone being a steroid, of course) in their brains. Additionally, exercise was one of the only things capable of reversing this phenotype. Exercise causes a rush of endorphins after training, which activate the same receptors (mu opioid) as morphine.

Stria Terminalis & Vasopressin

The stria terminalis is critical for the creation of vasopressin, and interestingly enough differs by gender. Men apparently have a larger one, producing more vasopressin (generally speaking). I ran across a reference to the stria terminalis in Susan Kuchinskas’ book The Chemistry of Connection, and decided I’d take a look around for some more info.

I ran across this interesting tidbit on Wikipedia:

The stria terminalis also appears to be indicated in gender identification. Male-to-female transsexuals have been found to have female-normative cell proliferation in the central subdivision of the bed nucleus of the stria terminalis (BSTc), whereas a female-to-male transsexual was found to have male-normative BSTc cell proliferation.[1][2] It is thought this is mediated by diminished and excessive androgen levels respectively in utero and neonatally.

One other thing I ran across that was interesting:

  • Loss or inhibition of a protein known as ASIC1a (acid sensing ion channel) common to the amygdala and bed nucleus of the stria terminalis leads to fearless behavior in mice. (via.)

Ventral Pallidum: Long-term Relationships, Monogamy, Oxytocin & More

I’m reading Susan Kuchinskas’ book The Chemistry of Connection, which despite having a pink cover with cute bunnies on it is not even remotely gender biased — she’s got a real strong focus on the actual scientific literature, and stacks of citations.. which is fantastic! At times she tries to “translate” the research into laymens terms, but then takes it back around to the technical. So far I’m very satisfied with it.

However, that’s entirely beside the point! Today’s blog post is actually, about the ventral pallidum, which she mentions on page 89.

I’ll quote the sentence that enticed this blog post:

Helen Fisher thinks that the same variations in vasopressin and oxytocin activity in the brain’s reward center and in the ventral pallidum, a structure that’s more active in long-term relationships, could also account for differences in “partner preference,” the early stage of courtship in which we identify that special someone we hope to make our own (Fisher, Aron, and Brown 2006).”

So, as I often do when I read something interesting about a brain region I’m unfamiliar with, I decided to peruse Eurekalert… Here’s a few of the goodies I found:

  • Rat’s ventral pallidum is activated more by sugar water than salt water, unless they’re salt deprived… under which circumstances the ventral pallidum is activated just as strongly as with sugar water. (via.)
  • “Scientists at Emory University have been able to increase bonding behavior in monogamous male prairie voles by transferring a receptor gene for the neuropeptide arginine vasopressin (AVP) into a particular region of the brain (the ventral pallidum).” [...] “Scientists previously have demonstrated that monogamy in voles, including the formation of pair bonds, is enhanced by vasopressin and that an antagonist for the vasopressin receptor can prevent the formation of pair bonding. Scientists also know that the distribution of the vasopressin receptor within certain regions of the brain is dramatically different between monogamous and non-monogamous species of voles. All monogamous vole species, even though they may be unrelated, have denser vasopressin receptor binding in the ventral pallidal region of the brain than do non-monogamous vole species.”(via.)
  • “[They] examined the distribution of two brain receptors in the ventral forebrain of monogamous prairie voles that have been previously tied to pair bond formation: oxytocin (OTR) and vasopressin V1a receptor (V1aR). Using receptor audiographic techniques, the scientists found that these receptors are confined to two of the brain’s reward centers, the nucleus accumbens and the ventral pallidum. V1aR receptors, which are thought to be activated in the male vole brain during pair bond formation, were confined largely to the ventral pallidum. OTR receptors, which play a crucial role in pair bond formation in females, were found mainly in the nucleus accumbens.” (via.)
  • “In the February 21 issue of the journal Science, the team will report that a small variation in the gene that encodes the enzyme called catechol-O-methyl transferase, or COMT, made a significant difference in the pain tolerance, and pain-related emotions and feelings, of healthy volunteers.”[...] The COMT protein is a sort of brain janitor, “cleaning up” the spaces between brain cells after chemicals called neurotransmitters finish sending signals between brain cells. Specifically, COMT metabolizes, or breaks down, the brain chemicals called dopamine and noradrenaline, also known as norepinephrine. Those with two copies of the val form of the gene make only powerful COMT that mops up dopamine rapidly. People with two copies of the met form of the gene make only poor COMT, and can’t “clean up” the dopamine in their brains very well. Those with one copy of each gene variety — the majority of people — make some of each kind of COMT, yielding a “normal” dopamine-metabolizing system. [...] And animal studies have shown that when the dopamine system is highly active, the brain reduces its production of other chemicals: the endogenous opioids, or so-called enkephalins. [...] Zubieta and his colleagues set out to see whether a person’s COMT genotype made a difference in their pain perception. They thought that perhaps those who metabolized dopamine very well because they had two val COMT genes would also be able to activate the brain’s painkilling system better than those with two copies of the met form of COMT. The results fit the predicted effect of COMT gene variation perfectly. Participants who had two copies of the met gene form could stand less of the painful injection than those with two copies of the val form of the gene, and their brains’ mu-opioid systems were less activated in many areas of the brain. [...] The differences between met/met and val/val participants in the activation of the mu-opioid system were most significant in the cingulate cortex, anterior thalamus, the thalamic pulvinar, and the basal ganglia, including the nucleus accumbens and ventral pallidum, and the amygdala. (via.)
  • “Our findings show that the brain areas activated when someone looks at a photo of their beloved only partially overlap with the brain regions associated with sexual arousal. Sex and romantic love involve quite different brain systems.” [...] Aron reported that, using functional magnetic resonance imaging (fMRI) and other measurements, he and his colleagues found support for their two major predictions: (1) early stage, intense romantic love is associated with subcortical reward regions rich with dopamine; and (2) romantic love engages brain systems associated with motivation to acquire a reward. [...] “Our data even may be relevant to some forms of autism,” Brown added. “Some people with autism don’t understand or experience any sort of emotional attachment or romantic love. I would speculate that autism involves an atypical development of the midbrain and basal ganglia reward systems.” [...] Another breakthrough, Brown noted, was that “we found several brain areas where the strength of neural activity changed with the length of the romance. Everyone knows that relationships are dynamic over time, but we are beginning to track what happens in the brain as a love relationship matures.” [...] Helen E. Fisher, a research anthropologist at Rutgers University, New Jersey, noted that not only did the brain change as romantic love endured, but that some of these changes were in regions associated with pair-bonding in prairie voles. The fMRI images showed more activity in the ventral pallidum portion of the basal ganglia in people with longer romantic relationships. (via.)
  • Disconnection studies have revealed that serial connections between basolateral amygdala, anterior cingulate cortex, nucleus accumbens, and ventral pallidum are involved in the exertion of effort and effort-related choice behavior (Floresco and Ghods-Sharifi, 2007; Farrar et al., 2008; Mingote et al., 2008; Hauber and Sommer, 2009). (via.)

Whew! I… may have broke a sweat. Anyhoo… This “ventral pallidum” area may be worth a google alert, I think.

Oh, before I forget… Make sure to check out Susan Kuchinskas’ websites:

Creativity, Depression, and DHEAS (a hormone that “blunts the effects of cortisol”)

Well, it turns out the cliché might be true after all: Angst has creative perks. That, at least, is the conclusion of Modupe Akinola, a professor at Columbia Business School, in her paper “The Dark Side of Creativity: Biological Vulnerability and Negative Emotions Lead to Greater Artistic Creativity.” The experiment was simple: She asked subjects to give a short speech about their dream job. The students were randomly assigned to either a positive or negative feedback condition, in which their speech was greeted with smiles and vertical nods (positive) or frowns and horizontal shakes (negative). After the speech was over, the subjects were given glue, paper and colored felt and told to create a collage using the materials. Professional artists then evaluated each collage for creativity.

In addition, Akinola also measured DHEAS (dehydroepiandrosterone), an endogenous hormone that blunts the effects of stress hormones like cortisol. (As I’ve written about before, depression is closely entangled with chronic stress.) Given this chemical power, it’s not surprising that low levels of DHEAS have been associated with susceptibility to volatile mood swings and downward spirals of sadness. Finally, subjects were also asked to self-report their moods, giving the scientists a subjective and objective measurement of how they were feeling, and how the feedback to the speech had shifted their emotional state.

Not surprisingly, positive feedback cheered us up: Participants who received smiles and nods during their speeches reported feeling better than before. Negative feedback had the opposite effect – it’s no fun having our dreams trampled on.

Here’s where things get interesting: People who received negative feedback created better collages, at least when compared to those who received positive feedback or no feedback at all. Furthermore, those with low baselines of DHEAS proved particularly vulnerable to the external effects of frowns, so that they proved to be the most creative of all. (via.)

Other interesting DHEAS tidbits:

Redheads require more anesthesia

Bask in the weirdness of this one:

Little known fact: Anesthetic requirement is increased in redheads. – “Red hair seems to be a distinct phenotype linked to anesthetic requirement in humans that can also be traced to a specific genotype.”

Weird just weird. Did I mention weird? Let’s talk about it. Comment if you think this is weird. If you don’t comment, I’ll assume you’re a redhead, and can’t respond because you’re testing your anesthetic-dose-requirement… Naughty, naughty.

    New press release “tries,” but still botches review of McGill “Marijuana” Study

    BusinessWeek, among others, published a new press release of the same McGill University “marijuana” study which, while at least mentioning that it was done on animals, still failed to mention several points — one of them being that the study itself did not even use marijuana, and in this case has the particularly large blight of outright stating that the rats were given cannabis, when in fact, they were given WIN 55212-2, a synthetic compound that is a stronger agonist of CB1 receptors  than tetrahydrocannabinol, the main active ingredient of marijuana (though there are a few others).

    If any of you recall, I made a post entitled “An unsurprisingly disingenuous look at marijuana” criticizing NOT the study itself, but the strong misrepresentation it was given on multiple popular science websites.

    Most of the ORIGINAL press this study got fell short in mentioning:

    • The study was in animals.
    • That the anxiety-like/depressive behavioral symptoms were not demonstrated in all of the results, and the study failed to demonstrate the same effects in the “open field test.”
    • That even the “low” dose may have been somewhat high, and thus not a good comparison for smoked marijuana, had it even been marijuana they tested in the first place.
    • And finally… That the study didn’t use marijuana, but instead a synthetic compound called WIN 55212-2, which has demonstrated both a stronger affinity for CB1 receptors than THC, and is structurally different. (which the news press release has done no better at)

    While I was quite pleasantly surprised that BusinessWeek (and the others hosting this new, updated press release), took the opportunity to mention that the study wasn’t done in humans:

    Although the finding stems solely from work conducted with adolescent and adult lab rats — not yet replicated among humans

    They still fell short in all other respects mentioned earlier, and in fact, explicitly and incorrectly stated that the rats were given cannabis, as shown:

    To assess the role cannabis may play on adolescent brain development, for 20 days — a period characterized as “prolonged exposure” — adolescent rats were given daily injections of either a low-dose (0.2 milligrams/kilograms) or high-dose (1.0 milligrams/kilograms) of cannabis.

    Round 2, still can’t get it right? Fire your PR department, McGill! Honestly.  A little proofreading, or a little honest (choose your slant) can go a long way.