Evidence for the Importance of Inflammation and Neurogenesis in Age-Related Cognitive Decline

Here I'll point out news of a recent study carried out in old rats, wherein the scientists involved claim a partial reversal of cognitive decline resulting from, probably, a reduction in chronic inflammation and increase in neurogenesis in the brain. The researchers pulled an existing drug from the rack for this experiment because it is known to affect the particular molecular targets they had in mind, but the results should be taken as a demonstration of the importance of inflammation and neurogenesis to brain aging, not as a sign that everyone should jump in and take that drug. It is only the particular tool of convenience for this study, and it is always wise to wait on replication of results and studies with larger numbers of animals in any case.

Neurogenesis is the term given to the production and integration of new neurons into the brain. It was only comparatively recently in the history of neuroscience, twenty to thirty years ago, that this process was proven to occur in adults. The consensus now is that a supply of new neurons is vital to learning and other forms of mental flexibility, and they have an effect on the overall behavior of neural networks that is large in comparison to their numbers. Unfortunately the pace of neurogenesis, like the pace of generation of new cells by stem cell populations throughout the body, declines with aging. This may be part of an evolved balance between death by cancer on the one hand and death by increasing frailty on the other. As molecular damage accrues to cells and tissues, created as a byproduct of the normal operation of cellular metabolism, too much cellular replication would speed the slow rise in the risk of fatal cancer. Conversely too little cellular replication will accelerate the slow decline into various forms of organ failure, nowhere more complex and subtle than in the brain.

Chronic inflammation contributes to a wide range of issues in aging, including most neurodegenerative conditions. The immune system runs awry and malfunctions with age, becoming ever more overactive and yet failing to accomplish its job at the same time. This excessive activity has consequences, including signals sent and received that change the behavior of cells and tissues. In short bursts this is necessary for regeneration and defense against pathogens, but when always on it causes harm. Higher levels of chronic inflammation resulting from metabolic dysregulation are probably one of the more important ways in which excess visceral fat tissue raises the risk of early death and of suffering all of the common age-related medical conditions along the way to that fate.

Will medical science produce the means to rescue people from the consequences of poor health and lifestyle choices? Yes, in the fullness of time. But that level of control - and reliability - remains a couple of decades away at least, I suspect. Metabolism is ferociously complex and still far from understood to the degree needed in order to create such science fiction staples such as safe obesity with perfect health. For the foreseeable future it is better not to get into that position in the first place, since at least some means of rejuvenation through repair of cell and tissue damage will probably arrive more rapidly. These are the important technologies to keep an eye on, as rising inflammation and lost neurogenesis are indirect consequences of this damage.

Old rat brains rejuvenated and new neurons grown by asthma drug

As we get older, most of us will experience some kind of brain degeneration. Typically, we lose the ability to make new neurons. Another problem is chronic, low-grade inflammation in the brain, which is implicated in many age-related brain disorders. To tackle both problems in one go, researchers targeted a set of receptors in the brain that, when activated, trigger inflammation. High numbers of these receptors are found in areas of the brain where neurons are born, suggesting they might also be involved in this process, too.

A drug called montelukast, regularly prescribed for asthma, blocks these receptors, so the researchers tried it on young and old rats. The team used oral doses equivalent to those taken by people with asthma. The older animals were 20 months old - roughly equivalent to between 65 and 75 in human years. The younger rats were 4 months old - about 17 in human years. The animals were fed the drug daily for six weeks, while another set of young and old rats were left untreated. There were 20 young and 14 old rats in total.

The rats took part in a range of learning and memory tests. By the end of their six-week drug regime, old animals performed as well as their younger companions. "We've restored learning and memory 100 per cent, to a level comparable with youth." When the team studied the brains of the animals, they found that old rats that had been given montelukast had 80 per cent less inflammation. They also had an enhanced level of new neuron growth compared with untreated old rats - about 50 per cent of that seen in young rats. The team also found that the blood-brain barrier - which stops infectious agents reaching the brain and which weakens in old age - was stronger in treated old rats. "Structurally, the brain had rejuvenated." The drug had no effect on young animals, probably because it targets inflammation associated with age and disease.

The researchers say the results from the rat study are significant enough to warrant a clinical trial, and will start by testing the drug in people with Parkinson's disease.

Comments

A neurogenetic drug called "Singulair"... I'm laughing. Can't wait for the clinicals.

Montelukast is known to have some neurological side effects, particularly in children, which is why it's not OTC. Shouldn't be surprising for what it is.

Wonder if it's worth trying to get a prescription of this stuff next year when allergy season hits...

Posted by: Slicer at October 24th, 2015 6:55 PM

@Slicer: "Wonder if it's worth trying to get a prescription of this stuff next year when allergy season hits..."

I won't wait till next year. House dust mites just became a huge problem for me.

Posted by: Waverunner at October 26th, 2015 2:04 AM

I've been taking Montelukast (10mg/day) for four months now. I wonder what neurological side effects Slicer refers to, and why he thinks it's funny? It's tiring to read blanket statements which lack citations of any kind.

I have noticed a loss of irritability and improved memory since I started taking it. I wish that I would've devised some tests to take before and after to be more scientific about it, but I knew that testing will soon begin and so I didn't. The only other effect that I've noticed is that my nose runs much less now when I'm out bicycling, which I've been doing for a couple of years.

Posted by: Rory at April 10th, 2016 1:18 AM

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