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Research analyzes neuroprotective effects of exercising

Memory improvement and reduction of damage caused by aging are among the benefits of exercising
Research analyzes neuroprotective effects of exercising

Studies show that moderate physical exercises might reduce the damage caused by brain ischemia, improve memory, and potentialize gene expression. - Picture by Gustavo Diehl

Author: Camila Raposo

Moderate physical exercises might reduce damage caused by brain ischemia, improve memory, potentialize gene expression, and even increase activation of enzymes that prevent Alzheimer. Those are some of the benefits found by the research that investigated the neuroprotective effect of exercising on animals. The study was led by Ionara Siqueira, a professor at UFRGS Department of Pharmacology of the Institute of Basic Health Sciences (ICBS).

The term neuroprotective refers to mechanisms and strategies used to protect neurons against damage caused by diseases that affect the Central Nervous System – such as neurodegenerative diseases, brain ischemia, or strokes. Diseases as ischemia cause interruption of the blood supply and consequently of oxygen supply in the brain, which can lead to neural cell death in brain regions that process memory  - such as hippocampus and striatum. The idea is to prevent diseases progression and to interrupt – or at to least delay – neuron death or dysfunction.  In cases of ischemia, for instance, neuroprotective agents can be used to limit the consequences of the disease and to avoid irreversible brain damage.

The studies that Professor Ionara Siqueira carried out started in 2016 and includes researchers from the Departments of Biochemistry and Physiology, and from the Neuroscience Post-Graduate Program. The group aimed to evaluate different exercise protocols concerning their effect on the reduction of ischemia-related damage. Thirty rats were divided into four groups – one group was subjected to moderate-intensity exercises, having 20 minutes of activity per day for two weeks; another group was subjected to high-intensity exercises, having 60 minutes of activity per day for two weeks, and the last two groups were not subjected to any type of exercise.

The rats were euthanized 16 hours after the experiment, their hippocampus were dissected and subjected to oxygen and glucose deprivation,   mimicking the effects of ischemia. They concluded that moderate-intensity exercises can reduce ischemia’s effects, while high-intensity activities increase the damage caused by the disease. Excess of exercises may increase oxidative stress and make the brain more vulnerable to the effects of ischemia due to the formation of free radicals.


Exercise and gene expression

The researchers adopted, then, an exercising pattern of 20 minutes in order to evaluate other parameters related to neuroprotection, such as histone acetylation and deacetylation.  Histones are proteins found in cell nuclei and wrapped by the DNA molecule, which have an important role in genes regulation.  In acetylation, the structure composed by histone and DNA is stretched, allowing higher levels of gene transcription, which includes those processes related to neuroprotective protein production and memory storing. Deacetylation, on the other hand, makes the structure more compact and reduces gene expression.

The tests showed that physical activity directly influences this process, increasing acetylation and reducing deacetylation. “Overall, we can say that physical exercise creates an environment that favors gene expression”, summarizes Siqueira. The effects, however, are transitory and only noticeable one hour after the activity is completed. According to her, this is an adaptation mechanism of our organism to avoid producing more substances than we need.


Aging and Memory


Another noticeable result is the effect of exercising on memory and anti-aging neuroprotection. There is evidence showing the role that neuroinflammation has in the brain-aging process, such as the increased proinflammatory cytokines levels, and reduction in anti-inflammatory cytokines levels. “The problem is that in order to fight increasing inflammation, proinflammatory cytokines also kill what they should not, such as neurons and glial cells.”, says Siqueira.

Experiments – with rats in different ranges of age submitted to 20 minutes of daily exercises for two weeks – show that exercises change neuroinflammatory markers in young and old rats in different ways. The exercises raised the levels of anti-inflammatory cytokines in young rats’ hippocampi. In old rats, anti-inflammatory cytokines levels remained stable, but proinflammatory cytokines levels dropped.

The same animals were submitted to memory tests. The younger rats presented better  memorizing abilities than the old ones. However, those who were submitted to the exercise routine presented superior results, regardless of their age – which shows the positive effects of physical exercises on memory. As it happens to gene expression, the memory improvement is transitory and it only occurs one hour after the activity is completed.

Studies also show that physical activity may increase the activation of the alpha secretaseenzymes, which is responsible for producing protective factors against Alzheimer’s disease during the aging process.

Tests with humans and research continuance


Studies with humans are in course, such as the one investigating the effects of physical activities on oxidative, inflammatory, and epigenetic parameters in patients with type 2 diabetes mellitus;  another study is investigating endurance runners. Both studies are carried out in collaboration with UFRGS School of Physical Education, Physical Therapy and Dance (Esefid). The research group also intends to continue the study and investigate the influence of physical activities on other regions of the brain, and the effects of different exercise routines.

Scientific papers
SIQUEIRA, I. et al. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiology of Learning and Memory, v. 101, p. 94-102, 2013.

SIQUEIRA, I. et al. Time-dependent effects of treadmill exercise on aversive memory and cyclooxygenase pathway function. Neurobiology of Learning and Memory, v. 98, p. 182-187, 2012.

SIQUEIRA, I. et al. Effect of different exercise protocols on histone acetyltransferases and histone deacetylases activities in rat hippocampus. Neuroscience, v. 192, p. 580-587, 2011.

SIQUEIRA, I. et al. Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation. Brain Research Bulletin, v. 71, p. 155-159, 2006.

Original text in Portuguese is available at:

Translated by Ana Nachtigall under the supervision of Professor Márcia Moura da Silva (UFRGS)

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