Running, cycling or other physical exercise are known to have multiple positive effect on human health, starting from improving cardiovascular function, decreasing incidence of the obesity up to elevated response to insulin in pre-diabetic and diabetic individuals. Moreover, during last decade it became clear that exercise affects not only our body, but also our mind. It has been known since a long time that physical exercise has a positive effect on our brain function. Reason, why we are taking a run to “clean our head” or to “figure out the solution” has its scientific explanation. Because it literally triggers “new brain connections” and “makes us happier”. Moreover, physical exercise, adequately planned and precisely enforced, in combination with proper nutrition, can be used as a therapeutic for multiple mental diseases such as depression, stress coping, compulsive disorder, Alzheimer, Huntington disease, dementia, anorexia nervosa, bulimia nervosa and ageing. But lets start from the beginning.

Biochemistry of beneficial effect of physical activity
In order to understand how we can use exercise, we have to get deep into its biochemistry. Mice which regularly “train” treadmill running show a differential expression of neurotransmitters in comparison to their sedimentary companions. Moreover “trained” mice exhibit multiple morphological changes of the brain with increased hippocampus-dependent memory and adult neurogenesis (Voss et al, 2013). Among factors, which are important in increase of neural plasticity, are BDNF and IGF1. Neural plasticity, which can be described as brain“reorganization” process, leads to creation of new or improvement of intra-neuronal communication, increase in cellular metabolism and increase in generation of new cells. Until recently, the concept of neurogenesis in adulthood was pretty controversial, since it was not known whether new neurons, generated in the hypocampus, have a function in cognition and brain repair. This changed beginning of 2000, when it has been reported that newly generated neurons in the adult mouse hippocampus have a correct neuronal morphology and membrane properties, as well as display functional synaptic inputs (van Praag et al, 2002). BDNF is one of the factor which is involved in increase in neurogenesis (Egeland et al, 2015).

1. BDNF – taking care of our mental health
More then ten years ago it has been shown that physical activity increments production of BDNF, a brain derived neurotrophic factor, which is responsible for prevention of neuronal cell death and is capable to trigger signalling inducing neural plasticity. Increase in BDNF expression, triggered by exercise, is regulated by two means. First, it has been shown that exercise induces expression of muscle protein FNDC5, identified as a precursor of irisin, a molecule associated with the browning of the fat. In addition to beneficial effect on the adipocyte tissue, FNDC5 also can increase expression of BDNF in brain (Wrann et al, 2013). Second manner how exercise increases BDNF expression is through production of particular metabolites, which in turn affect epigenetic landmarks of genes (Koppel et al, 2013). Sleiman et al shown that exercise induces the accumulation of a ketone body (D-β-hydroxybutyrate or DBHB) in the hippocampus, where it serves both as an energy source and an inhibitor of class I histone deacetylases (HDACs, proteins involved in the epigenetic modifications) to specifically induce BDNF expression (Sleiman et al, 2016).
Why BDNF is so important? There are multiple research data underline involvement of BDNF in conditions such as schizophrenia, depression, compulsive disorder, Alzheimer, Huntington disease, dementia, anorexia nervosa, bulimia nervosa and stress. It has been observed that schizophrenia development correlates with low levels of BDNF expression during process of brain development, triggering inadequate brain morphology and signalling (Nieto et al, 2013). Incidence in schizophrenia and eating disorders, such as anorexia and bulimia nervosa, have been associated with one dysfunctional variation of BDNF, which contains single nucleotide change, called as single nucleotide polymorphism (SNP) (Gratacòs et al, 2006). People suffering from major depression disorder or undergoing sustained emotional stress have decreased levels of BDNF (Lee et al, 2010). Curiously, as a prove of concept, it has been shown that several classes of antidepressants (monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic agents (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs) can increase BDNF expression in the brain when given to healthy rodents (Lee et al, 2010).
How to increase expression of BDNF? Well, though it can be achieved chemically, it is much better to look for another solution than turning towards synthetic “happy pills”. It has been shown that exhaustive exercise leads to increase in this factor inside the blood serum (Rojas Vega et al, 2006). Low intensity exercise, on the other hand, showed no changes in the BDNF serum level in healthy individuals (Maass et al, 2015). The same goes with resistance training, which though is able to increase muscular mass, does not affect BDNF expression (Antonio-Santos et al, 2016). Interestingly, two new studies came out recently showing positive correlation between increased BDNF secretion and activity of mitochondria complex I and correlated with it oxidative stress (Roh et al, 2016; Gusdon et al, 2017). This, once again, underlines a beneficial effect of ROS upon aerobic training (so better no post training antioxidants packs!)

YMAZING Exercise! How to get happy and mentally fit!

2. IGF1
Increase in growth factors have been always associated with increased neuronal plasticity, where its decline is associated with age-associated decline in cognitive functions. Exercise selectively increases insulin-like growth factor-I (IGF-1) expression in the rat hippocampus, triggering an increase in the number of new neurons (Trejo et al, 2001) and cerebral vascular density (Lopez-Lopez et al, 2004). Therefore regularly exercising rats exhibit IGF1 dependent neuronal and cognitive enhancement and memory in the hippocampus (Ding et al, 2006).
IGF1 is mainly produced and released from the liver, but also can be produced in numerous tissues including neurons, glia, and vascular cells. IGF1 expression have been shown to be positively regulated by growth hormone (GH) (Yan et al, 2011). Unlike BDNF, IGF1 expression can be induced by acute resistance exercise (Schwarz et al, 2016; Kido et al, 2016).

3. Adiponectin – more then fat cells and inflammation
Physical exercise have been shown to have an antidepressant feature by inducing production of adiponectin. This can raise the possibility of treating depression states with boost of aerobic exercise or by adiponectin treatment (Yau et al, 2014).

4. Kynurenic acid
Stress-induced depression is a condition, which has a profound impact on quality of life of nowadays society. Physical expertise have bee shown to induce expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid (Agudelo et al, 2014). Kynurenic acid is a product coming from correct metabolism of tryptophan and possesses neuroactive activity, acting as antiexcitotoxic and anticonvulsant. Curiously, it has been shown that adult rats, being on the ketogenic diet, have increased concentration of this acid (Żarnowski et al, 2011).

To sum up: Application
Not everyone posses high expression of “sport gene”, not everyone has to win races, but it is important to implement some changes in our life style. Those steps will not only improve our body function, but also will make us happy, efficient and joyful. Already during pregnancy, it has been shown that exercising pregnant mice help to improve spatial learning and short-term memory in their offspring (Robinson et al, 2014). We have to motivate our kids to move, play, run. Epidemiological studies, performed on the school kids (age 4–18 years) showed that regular physical activity during their childhood led to increased cognitive function, improved intelligence, school achievements, mathematics, memory, developmental and academic reediness (Sibley et al, 2003). Adulthood, apart from independency, fun, comes in package with responsibility and stress. It has been shown that regular exercise regiment (3 times a week, 1 hour of high intensity training) leads to improvement of anxiety and depression conditions. Though our cognitive function decline with age, there are multiple research data and epidemiological studies which show a positive correlation between physical exercise and improvement in brain function and cognition (Duzel et al, 2016). Based on the research data coming from humans and evidence from animals suggest that minimal time to achieve an improvement is 3-6 months of moderate to high intensity exercise (Duzel et al, 2016). To preserve mental functions: mild-to-moderate intensity, 50–70% of max. cardiac output performed during 12 months with 30–40-min sessions 3 times a week (Duzel et al, 2016). To improve mental function: moderate-to-high >75% of max. cardiac output, performed during 3-6 months with 30–40-min sessions with high intensity intervals of 4 × 5 min (Duzel et al, 2016).

YMAZING Exercise! How to get happy and mentally fit!  YMAZING Exercise! How to get happy and mentally fit!

So, independently of age and sex, lets keep moving!
My option: get a cheap Ryanair tickets to Canarias and instead of a renting a car, rent a road bike and discover the island! When you reach Puerto de las Nieves, get some nice tortilla (tryptophan) and top up your Vitamin D.

YMAZING Exercise! How to get happy and mentally fit!  YMAZING Exercise! How to get happy and mentally fit!  YMAZING Exercise! How to get happy and mentally fit!
-> Importance of those two will discuss in the next article!

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