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How physical exercise protects the brain from stress-induced depression

Physical exercise has many beneficial effects on human health, including the protection from stress-induced depression. However, until now the mechanisms that mediate this protective effect have been unknown. In a new study in mice, researchers at Karolinska Institutet in Sweden show that exercise training induces changes in skeletal muscle that can purge the blood of a substance that accumulates during stress, and is harmful to the brain. The study is being published in the prestigious journal Cell.

“In neurobiological terms, we actually still don’t know what depression is. Our study represents another piece in the puzzle, since we provide an explanation for the protective biochemical changes induced by physical exercise that prevent the brain from being damaged during stress,” says Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institutet.

It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).

These mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behaviour, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.

“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain. We actually found the opposite: well-trained muscle produces an enzyme that purges the body of harmful substances. So in this context the muscle’s function is reminiscent of that of the kidney or the liver,” says Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet.

The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness. In this study, the researchers demonstrated that when normal mice were given kynurenine, they displayed depressive behaviour, while mice with increased levels of PGC-1a1 in muscle were not affected. In fact, these animals never show elevated kynurenine levels in their blood since the KAT enzymes in their well-trained muscles quickly convert it to kynurenic acid, resulting in a protective mechanism.

“It’s possible that this work opens up a new pharmacological principle in the treatment of depression, where attempts could be made to influence skeletal muscle function instead of targeting the brain directly. Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness,” says Jorge Ruas.

Depression is a common psychiatric disorder worldwide. The World Health Organization (WHO) estimates that more than 350 million people are affected.

People want to believe gender is something that’s essential, and people repeat these essentialist ideas all the time. ‘Oh, women do that’ and ‘Oh, men do that’ and the reality is that all women don’t anything. We as individuals do what we do, you know, and sometimes that’s informed by gender and sometimes it’s just who we are. And I think all that just makes people really, really uncomfortable because they don’t want to think about who they are.

Laverne Cox (via lucrezialoveshercesare)

I will keep auto-reblogging until it sinks in.

(via carnivaloftherandom)

ucsdhealthsciences:

Scientists Discover “Dimmer Switch” For Mood Disorders

Researchers at University of California, San Diego School of Medicine have identified a control mechanism for an area of the brain that processes sensory and emotive information that humans experience as “disappointment.”

The discovery of what may effectively be a neurochemical antidote for feeling let-down is reported Sept. 18 in the online edition of Science.

“The idea that some people see the world as a glass half empty has a chemical basis in the brain,” said senior author Roberto Malinow, MD, PhD, professor in the Department of Neurosciences and neurobiology section of the Division of Biological Sciences. “What we have found is a process that may dampen the brain’s sensitivity to negative life events.”

Because people struggling with depression are believed to register negative experiences more strongly than others, the study’s findings have implications for understanding not just why some people have a brain chemistry that predisposes them to depression but also how to treat it.

Specifically, in experiments with rodents, UC San Diego researchers discovered that neurons feeding into a small region above the thalamus known as the lateral habenula (LHb) secrete both a common excitatory neurotransmitter, glutamate, and its opposite, the inhibitory neurotransmitter GABA.

Excitatory neurotransmitters promote neuronal firing while inhibitory ones suppress it, and although glutamate and GABA are among two of the most common neurotransmitters in the mammalian brain, neurons are usually specialists, producing one but not both kinds of chemical messengers.

Indeed, prior to the study, there were only two other systems in the brain where neurons had been observed to co-release excitatory and inhibitory neurotransmitters – in a particular connection in the hippocampus and in the brainstem during development of the brain’s auditory map.

“Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway,” said lead author Steven Shabel, a postdoctoral researcher with Department of Neurosciences and neurobiology section of the Division of Biological Sciences. “In our case, that pathway is believed to signal disappointment.”

The LHb is a small node-like structure in the epithalamus region of the brain that is critical for processing a variety of inputs from the basal ganglia, hypothalamus and cerebral cortex and transmitting encoded responses (output) to the brainstem, an ancient part of the brain that mammals share with reptiles.

Experiments with primates have shown that activity in the LHb increases markedly when monkeys are expecting but don’t get a sip of fruit juice or other reward, hence the idea that this region is part of a so-called disappointment pathway.

Proper functioning of the LHb, however, is believed to be important in much more than just disappointment and has been implicated in regulating pain responses and a variety of motivational behaviors. It has also been linked to psychosis.

Depression, in particular, has been linked to hyperactivity of the LHb, but until this study, researchers had little empirical evidence as to how this overstimulation is prevented in healthy individuals given the apparent lack of inhibitory neurons in this region of the brain.

"The take-home of this study is that inhibition in this pathway is coming from an unusual co-release of neurotransmitters into the habenula," Shabel said. Researchers do not know why this region of the brain is controlled in this manner, but one hypothesis is that it allows for a more subtle control of signaling than having two neurons directly counter-acting each other.

Researchers were also able to show that neurons of rodents with aspects of human depression produced less GABA, relative to glutamate. When these animals were given an antidepressant to raise their brain’s serotonin levels, their relative GABA levels increased.

"Our study suggests that one of the ways in which serotonin alleviates depression is by rebalancing the brain’s processing of negative life events vis-à-vis the balance of glutamate and GABA in the habenula," Shabel said. "We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences."

Pictured: Basal ganglia neurons (green) feed into the brain and release glutamate (red) and GABA (blue) and sometimes a mix of both neurotransmitters (white).

!!!

thebicker:

charles-a-green:

charles-a-green:

tank-grrl:

hello-missmayhem:

cptprocrastination:

doomhamster:

belcanta:

nikkidubs:

attentiondeficitaptitude:

belcanta:

Guaranteed basic income to every citizen, whether or not they are employed to ensure their survival and that they live in a dignified, humane way, preventing poverty, illness, homelessness, reducing crime, encouraging higher education and learning vocations as well as helping society become more prosperous as a whole. 

Wow. Forget raising the minimum wage. This is much much better idea.

The minimum wage could actually drop if we had basic income.

But Americans would never go for it. Miserably slogging through 12 hour days and having businesses open 24/7 is too engrained in our culture.

"BUT WHERE WILL THE GOVERNMENT GET THE MONEY?" screamed Joe Schmoe, slamming a meaty fist onto the table and getting mouth-froth all over the front of his greying tank top. "You libt*rds all think money grows on TREES!! HAHA!"

"But where will people get the incentive to work?!" Mindy Bindy cried, flapping her hands in front of her face. She’d had a fear of the unemployed lollygagging about ever since she was a child and her mother told her to be afraid of the unemployed lollygagging about. "You think people should get paid for nothing? I work hard for my money!”

"But who will serve me?" grumbled Marty McMoneybags. "Who will make me feel important? Who will do my laundry and cook my food and stand in front of me wearing a plastic smile while I take out all my stress—because I do have a lot of stress, you know, being this rich is stressful—on them?” He paused and straightened out the piles of hundred dollar bills on the desk in front of him, then raised his two watery, outraged eyes up to the Heavens. “Lord, if there are no poor people, how will I know that I’m rich??”

I laughed. This is perfect! Well said!

The thing is, while I’m sure you could scrape up a few people who’d be willing to just float by on a guaranteed minimum income? For most people the choice to work would be a no-brainer. “Hmmm. I can get by on 33k a year, or I can take that part time job and make 48k… enough to move to a better apartment, maybe take the family on vacation. Sold.” Hell, most people would want to work simply because it gives one a sense of dignity and something to do with one’s time. (Speaking as someone who’s been unemployed, on extended sick leave, etc. in her time, the boredom and sense of isolation that comes with not having a job is almost as bad as the humiliation of having to depend on other people for one’s survival.)

And with this system, part-time jobs and “non-skilled” jobs would be much more readily available because nobody would need to work two or three jobs just to stay afloat!

Which would ALSO mean that employers and customers couldn’t shamelessly exploit employees the way they can today, because if losing a job weren’t necessarily a financial disaster, more people would be willing to walk out on jobs where they weren’t being treated with dignity.

And if this also applies to students (and it should) then student loans would become much less of a problem, and fewer people would flunk out of school because of having to juggle studies and work.

Far fewer people would be forced to stay with abusive partners, parents or roommates because they couldn’t afford to move out.

And the thing is, all those people who suddenly had money? They’d be spending it. They’d be getting all the stuff they can’t afford now - new clothes, books, toys, locally-produced food, car repairs - and with each purchase money would flow BACK to the government, because VAT, also income tax.

The unemployed and/or disabled wouldn’t need special support any more - which would also mean the government could fire however many admins who are currently engaged in humiliating - *cough* making sure those people aren’t getting money they don’t deserve. Same for medical benefits and pensions. And I’m no legal scholar, but I somehow imagine less financial desperation would lead to less petty crime, and hence less need for police and security everywhere?

TL;DR Doomie thinks this is a good idea, laughs at those who protest.

reblogging for more top commentary

They tried something like this out in Canada as a sort of social experiment, called Mincome. What they found was that, on the whole, people continued to work about as much as they did before. Only new mothers and teenagers worked substantially less hours. 

But wait, there’s more. Because parents were spending just a little more time at home and involved with their families, test scores increased. Because teens didn’t have to work to support their families, drop-out rates decreased. Crime rates, hospital visits, psychiatric hospitalizations and domestic abuse rates all dropped, as well. More adults pursued higher education. Those who continued to work reported more job flexibility and more opportunity to choose employment they preferred.

Basically, now you can go prove to your asshole family members that society won’t collapse without poor people for you to feel better than.

The picture is awesome, but read the commentary, that’s what I’m reblogging for.

This is wonderful commentary and I really really hope that we can have something like this in the US

I’m reblogging this TWICE because I love it that much

A couple things worth noting:

The "mincome" experiment didn’t run in all of Canada — just in one town. It was in the late 1970s, but the results weren’t analyzed and published until just a few years ago. Here’s an interview with the researcher who analyzed the outcome. TL;DR version: It went really well. But the experiment only lasted five years and has never been repeated anywhere else.

The idea of a guaranteed minimum income has gained popularity with a surprising group: Libertarians. The government would theoretically abolish Social Security, welfare, food stamp programs, disability, and other social programs and replace it with “here is the amount of money everyone gets no matter what.” It would drastically reduce the size of government, which gets those Ron Paul folks on board. And it would eliminate poverty (assuming the minimum income was at or above the poverty line), which gets us bleeding-heart types on board. Obviously, opponents include big banks (who make money processing food stamps, among other things) and every person who considers poverty a moral failing (the wealthy, the entire Republican party, that one uncle everyone has who you dread getting seated next to at Thanksgiving). Also, some elderly people, since a minimum guaranteed income might be lower than their current Social Security benefits.

I think, if nothing else, it’s worth a try. However, given the political climate, “let’s give free money to everyone!” is not a home run as far as potential legislation goes.

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