Deleterious Effects Of Brain Activity / Thinking

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#1
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Source: University of Rochester Medical Center
Date: 2005-11-04
Bad Thoughts

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Scientists Show How Thinking Can Harm Brain Cells

Scientists at the University of Rochester Medical Center have targeted a new culprit and method of attack on neurologic functions in diseases such as Alzheimer's and dementia associated with HIV.

In an article in the Nov. 1 issue of The Journal of Clinical Investigation, the Rochester scientists describe a new mechanism by which brain cells can be damaged during chronic neurodegenerative diseases. When inflammation occurs in the brain, nerve impulses that are passed between cells during routine activities like learning and memory can become toxic. Instead of triggering the formation of memories, these impulses can inflict injury on neurons and disrupt neurologic function.

Understanding this mechanism could provide a new path for drugs to treat the diseases. Working in collaboration with researchers at the University of California at San Diego, the Rochester scientists propose a strategy of chemical preconditioning to induce adaptations in nerve cells that would enable the cells to better withstand toxic attacks, prevent injury, and preserve function.

"Preconditioning would allow the nervous system to experience stress and become more resistant to future encounters with stress and the damage it can trigger," said Harris A. Gelbard, M.D., professor of Neurology at the University of Rochester Medical Center and the research project's principal investigator.

A long-standing villain in neurodegenerative disease has been glutamate, an amino acid that normally acts as a neurotransmitter. Excess glutamate, however, can overly excite neurons, causing damage and death -- a process called excitotoxicity. Some drugs developed for the treatment of Alzheimer's disease, for example, are designed to lower the production of glutamate or block its transmission to reduce excitotoxic injury.

"But just blocking glutamate doesn't seem to work efficiently in neurodegenerative diseases with inflammation," said Gelbard. "We reconsidered how excitotoxicity actually damages the nervous system in a functional way."

The scientists focused on dendrites, the crooked branches of neurons that carry impulses toward the body of the nerve cell, and synapses, the places where impulses pass from neuron to neuron. Injury to dendrites -- characterized by swelling or beading, loss of dendrite spines, and reduction in size -- is seen in HIV-1-associated dementia and Alzheimer's.

In laboratory studies, brain cells and slices were exposed to platelet-activating factor, or PAF, a compound that promotes inflammation and plays many roles in the brain. It can be produced by neurons and takes part in the working of synapses, including activity associated with learning and remembering. It also is produced by immune cells during inflammation. The amount of PAF in the brain increases dramatically in HIV-1-associated dementia and other neurodegenerative diseases.

"We found that disease makes dendrites more vulnerable to excitotoxicity," said Matthew J. Bellizzi, a researcher and student in the M.D./Ph.D. program at the Medical Center and corresponding author of the journal article. "We also found that damage to the dendrites may not require abnormal glutamate exposure."

The lab studies showed that elevated levels of PAF promoted beading on dendrites and injury to synapses following bursts of synaptic activity similar to those thought to be involved in learning and memory.

"This mechanism does not just apply to HIV," Gelbard said. "It applies to Alzheimer's, multiple sclerosis, Parkinson's and any neurodegenerative diseases that have synaptic dysfunction with inflammation, which is virtually all of them."

In lab studies, brain cells were treated with diazoxide, a drug investigated for use in ischemic heart disease and strokes. Pretreatment before exposure to PAF prevented dendritic beading and preserved synaptic functions, the studies showed.

"Stressing the cells with small amounts could trigger protective genes and induce adaptations that will make the dendrites more able to withstand insults," Bellizzi said.

Diazoxide is not the only drug that would work, and others might be better, the researchers said. Memantine, a drug that blocks glutamate receptors, is used in the treatment of Alzheimer's. Chemical preconditioning could represent an alternate or complementary strategy.

"Preconditioning to protect the synapse is likely to be more important in the early and middle phases of neurodegenerative diseases than simply preserving the cell body," Gelbard said.



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The research was supported by grants from the National Institutes of Health.

In addition to Gelbard and Bellizzi, the research team included Shao-Ming Lu, Ph.D., research assistant professor of Neurology at the Medical Center, and Eliezer Masliah, M.D., professor of Neuroscience and Pathology at the University of California at San Diego.
 
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Anonymous

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#3
Thanks for the article: I've got two exams in a month time relating to this area - Cognitive Neuroscience and 'brain and behaviour' - this should give me some room to blag when I am stuck!!! :D
 

bazizmaduno

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#4
i've always known that thinking ain't good for you - i stopped doing that years ago..... :D
 
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Anonymous

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#6
Ah, well if you've stopped thinking clearly astrology and mediumship are the topics for discussion :rofl:
 

headnspace

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#7
my brain's full

I went through about 10 years of college/grad school. I hit a point where my brain "got full" and learning new stuff made other stuff fall out of my head.

I figured it was time to quit learning, and go earn some money.
:p
 

EnolaGaia

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#8
On a disturbingly similar note ... Recent research suggests "excessive" thinking or brain activity may be correlated with shortened lifespans.
'Excessive' Brain Activity Has Been Linked to a Shorter Life

One key to a longer life could be a quieter brain without too much neural activity, according to a new study that examined postmortem brain tissue from extremely long-lived people for clues about what made them different from people who died in their 60s and 70s.

"Use it or lose it" has dominated thinking on how to protect the aging brain, and extensive research shows there are many benefits to remaining physically and mentally active as people get older.

But the study, published in the journal Nature, suggests more isn't always better. Excessive activity - at least at the level of brain cells - could be harmful.

"The completely shocking and puzzling thing about this new paper is … [brain activity] is what you think of as keeping you cognitively normal. There's the idea that you want to keep your brain active in later life," said Michael McConnell, a neuroscientist at the Lieber Institute for Brain Development, who was not involved in the study.

"The thing that is super unexpected is … limiting neural activity is a good thing in healthy aging. It's very counterintuitive."

Researchers at Harvard Medical School analyzed brain tissue donated to human brain banks by people ranging in age from their 60s and 70s to centenarians who lived to be 100 or older.

They found people who died before their mid-80s had lower levels in their brains of a protein called REST that tamps down genes involved in sparking brain activity, compared to the very oldest people. REST had already been shown to be protective against Alzheimer's disease.

But they weren't sure whether REST somehow protected people from death or was just a sign of further aging.

Since it is not currently possible to measure REST in the brains of living people, the scientists began experiments in roundworms and mice to test whether it plays a role in life span.

When researchers increased the activity of a worm version of REST, the worms' brain activity decreased and they lived longer. The opposite happened when scientists disabled the REST-like gene in "Methuselah" roundworms that have very long life spans; the worms' neural activity increased - and their lives were dramatically shortened.

Mice lacking REST were also more likely to have busier brains, including seizure-like bursts of activity.

"I think this is overactivity, out-of-control excitation - it's not good for the brain. You want the neurons to be active, when and where you want them to be active, not to be just generally firing off," said Cynthia Kenyon, vice president of aging research at Calico Labs, who praised the study design but said she thinks the nervous system is just one of the many tissues that have an influence on life span.

It's not yet clear how these differences in brain activity at the level of cells could translate to differences in cognition or behavior in people. ...
FULL STORY: https://www.sciencealert.com/excessive-brain-activity-has-been-linked-to-a-shorter-life
 

kamalktk

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#9
On a disturbingly similar note ... Recent research suggests "excessive" thinking or brain activity may be correlated with shortened lifespans.
Anxiety/stress causing shortened lifespans? After all anxiety is characterized by overthinking, and produces a number of negative physical effects.
 

EnolaGaia

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#10
Anxiety/stress causing shortened lifespans? After all anxiety is characterized by overthinking, and produces a number of negative physical effects.
That's one of the angles that occurred to me, too.

I'm not sure the researchers were able to characterize the particular type(s) of brain activity / "thinking" most closely associated with the decrease in the REST protein. As a result, I don't believe there's (yet) reason to assume the protein interference is specifically associated with stressful "thinking".
 
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