Powerful effect of exercise against Alzheimer's . . . Exercising for 150 minutes each week may be the best treatment for Alzheimer's, according to a study published in the Journal of Alzheimer's Disease. Researchers from the University of Maryland School of Public Health (College Park) conducted the study, which reveals that exercise could improve cognitive function in people at risk of Alzheimer's by improving the efficiency of brain activity. The study analyzed 17 participants with mild cognitive impairment (MCI) – early memory loss associated with Alzheimer's disease – alongside 18 controls. Both groups were of similar age, gender, education, genetic risk and had similar medication use. The participants were asked to carry out a 12-week exercise program, which consisted of walking on a treadmill at moderate intensity while being supervised by a personal trainer. Before and after the exercise program, both groups were asked to complete memory tests. The first was a fMRI famous name discrimination task. This is a memory test requiring the participants to identify famous names as their brain activity was measured. The second was a list learning task. This test involved the participants recalling words read to them from a list over five consecutive attempts, and again after being distracted with a different list. Results of the study showed that both groups improved their fitness levels by around 10%. But the fMRI test taken after the exercise program revealed a significant increase in the intensity of brain activation in 11 brain regions as the participants correctly identified famous names. The areas of the brain activated with improved efficiency were the same areas of the brain that lead to a diagnosis of Alzheimer's disease. The areas included were the precuneus region – the area involved in episodic memory, the temporal lobe and the parahippocampal gyrus – an area that plays a role in memory encoding and retrieval. Carson Smith, MD, assistant professor in the Department of Kinesiology at the university, said: "We found that after 12 weeks of being on a moderate exercise program, study participants improved their neural efficiency – basically they were using fewer neural resources to perform the same memory task. No study has shown that a drug can do what we showed is possible with exercise." Results of the study also showed improved memory recall within the list learning task. The researchers said that what makes these results even more interesting is that these results were achieved using the levels of exercise that are in line with physical activity recommendations for older adults. The guidelines encourage moderate intensity exercise over most days, totaling 150 minutes each week, the researchers add.

Learning (and adapting) under stress . . . Whenever we have to acquire new knowledge under stress, the brain deploys unconscious rather than conscious learning processes. Neuroscientists at the Ruhr-Universitat Bochum (Bochum, Germany) have discovered that this switch from conscious to unconscious learning systems is triggered by the intact function of mineralocorticoid receptors. These receptors are activated by hormones released in response to stress by the adrenal cortex. The team of Lars Schwabe from the Institute of Cognitive Neuroscience, together with colleagues from the neurology department at the university clinic Bergmannsheil, reports in the journal Biological Psychiatry. The team from Bochum has examined 80 subjects, 50% of whom were given a drug blocking mineralocorticoid receptors in the brain. The remaining participants took a placebo drug. Twenty participants from each group were subjected to a stress-inducing experience. Subsequently, all participants underwent a learning test, the so-called weather prediction task. The subjects were shown playing cards with different symbols and had to learn which combinations of cards meant rain and which meant sunshine. The researchers used MRI to record the respective brain activity. There are two different approaches to master the weather prediction test: some subjects tried consciously to formulate a rule that would enable them to predict sunshine and rain. Others learned unconsciously to give the right answer, following their gut feeling, as it were. The team of Lars Schwabe demonstrated in August 2012 that, under stress, the brain prefers unconscious to conscious learning. "This switch to another memory system happens automatically," said Lars Schwabe. "It makes sense for the organism to react in this manner. Thus, learning efficiency can be maintained even under stress." However, this works only with fully functional mineralocorticoid receptors. Once the researchers blocked these receptors by applying the drug Spironolactone, the participants switched over to the unconscious strategy less frequently, thus demonstrating a poorer learning efficiency. These effects also became evident in MRI data. Usually, stress causes the brain activity to shift from the hippocampus – a structure for conscious learning – to the dorsal striatum, which manages unconscious learning. However, this stress-induced switch took place only in the placebo group, not in subjects who had been given the mineralocorticoid receptor blocker. Consequently, the mineralocorticoid receptors play a crucial role in enabling the brain to adapt to stressful situations.

Hope for motion sickness victims . . . It happens at least once each winter in the climate of Montreal. You're walking on the sidewalk and before you know it you are slipping on a patch of ice hidden under a dusting of snow. Sometimes you fall. Surprisingly often you manage to recover your balance and walk away unscathed. McGill (Montreal) researchers now understand what's going on in the brain when you manage to recover your balance in these situations. And it is not just a matter of good luck. Kathleen Cullen and her PhD student Jess Brooks of the Dept. of Physiology have been able to identify a distinct and surprisingly small cluster of cells deep within the brain that react within milliseconds to readjust our movements when something unexpected happens, whether it is slipping on ice or hitting a rock when skiing. What is astounding is that each individual neuron in this tiny region that is smaller than a pin's head displays the ability to predict and selectively respond to unexpected motion. This finding both overturns current theories about how we learn to maintain our balance as we move through the world, and also has significant implications for understanding the neural basis of motion sickness. Scientists have theorized for some time that we fine-tune our movements and maintain our balance, thanks to a neural library of expected motions that we gain through "sensory conflicts" and errors. "Sensory conflicts" occur when there is a mismatch between what we think will happen as we move through the world and the sometimes contradictory information that our senses provide to us about our movements. This kind of "sensory conflict" may occur when our bodies detect motion that our eyes cannot see (such as during plane, ocean or car travel), or when our eyes perceive motion that our bodies cannot detect (such as during an IMAX film, when the camera swoops at high speed over the edge of steep cliffs and deep into gorges and valleys while our bodies remain sitting still). These "sensory conflicts" are also responsible for the feelings of vertigo and nausea that are associated with motion sickness. But while the areas of the brain involved in estimating spatial orientation have been identified for some time, until now, no one has been able to either show that distinct neurons signaling "sensory conflicts" existed, nor demonstrate exactly how they work. "We've known for some time that the cerebellum is the part of the brain that takes in sensory information and then causes us to move or react in appropriate ways," said Cullen. "But what's really exciting is that for the first time we show very clearly how the cerebellum selectively encodes unexpected motion, to then send our body messages that help us maintain our balance. That it is such a very exact neural calculation is exciting and unexpected." By demonstrating that these "sensory conflict" neurons both exist and function by making choices "on the fly" about which sensory information to respond to, Cullen and her team have made a significant advance in our understanding of how the brain works to keep our bodies in balance as we move about. The research was done by recording brain activity in macaque monkeys who were engaged in performing specific tasks while at the same time being unexpectedly moved around by flight-simulator style equipment.

Parkinson's in men may be linked to testosterone decline . . . Parkinson's disease in men may be linked to a sudden decline in testosterone, a study published in The Journal of Biological Chemistry suggests. Researchers at Rush University Medical Center (Chicago) analyzed a number of male mice who had been castrated, dramatically decreasing their testosterone levels, and they found that the mice showed increased symptoms of Parkinson's disease. Kalipada Pahan, MD, professor of neurology at the university, explains: "While scientists use different toxins and a number of complex genetic approaches to model Parkinson's disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson's-like pathology and symptoms in male mice." However, the researchers add that when the mice were given supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets, the symptoms of Parkinson's disease were reversed. According to the researchers, in healthy males, testosterone is at its maximum levels in the mid-30s, gradually decreasing each year after then by around 1%. But they add that testosterone levels could also dramatically drop as a result of stress or other sudden life-changing events. "In men, testosterone levels are intimately coupled to many disease processes. Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson's disease," said Pahan.Parkinson's disease is a disorder of the nervous system, which can affect how a person moves. Symptoms are progressive, usually beginning with small tremors in one hand. The study authors say that from this research, it is apparent that understanding how Parkinson's disease works is important for developing drugs that protect the brain and halt progression. They add the research suggests nitric oxide – a gas naturally produced in the body that communicates between cells – is an important molecule for developing these drugs.

— Compiled by Robert Kimball, MDD Staff Writer

robert.kimball@ahcmedia.com

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