Summary: Researchers report physical exercise failed to promote antidepressant-like effects in mice genetically engineered to express a human genetic variation in the gene BDNF.
Source: University of Milan
Physical exercise has several beneficial effects on human wellbeing, including anxiolytic and antidepressant effects. However, there are individual differences in response to regular physical exercise. A new study, recently published in Neuropsychopharmacology, suggests that these individual variabilities may be accounted for by specific genetic variants.
Researchers from the University of Milan, in collaboration with the Weill Cornell Medical College, reported that physical exercise failed to promote anxiolytic, and antidepressant, like effects in mice genetically engineered to express a human genetic variation in the gene for the brain-derived neurotrophic factor (BDNF).
BDNF is a neurotrophin highly expressed in the adult brain modulating neuronal plasticity. The term neuronal plasticity refers to the capability of brain cells to reorganize pathways and connection throughout life in response to environmental stimuli. A human genetic variant of BDNF, named Val66Met, is carried by approximately 30% of individuals; and some previous studies have shown that this variant is associated with size reduction of specific brain regions and an increased susceptibility to develop neuropsychiatric and neurodegenerative diseases.
The researchers wanted to know how the presence of the BDNF genetic variant could affect the response to physical exercise in mice. To find out, they allowed some groups of mice to voluntarily run on a cage wheel for a month. Behavioral analyses were then performed on mice, showing that physical exercise-induced anxiolytic- and antidepressant-like response was compromised in mutant mice carrying the BDNF genetic variant.
In addition to the behavioral testing, the researchers also performed some molecular analyses finding that, after physical exercise, the levels of BDNF were increased in the hippocampus, a region important for memory and mood regulation, only in wild-type mice but not in mice carrying the BDNF genetic variant.
An important question is how physical exercise may control the expression of certain genes in the brain and their function. Some recent studies have highlighted the importance of specific factors released from the muscle in modulating such responses. Interestingly, the research have found that one of these factors, called FNDC5, normally increased by regular physical exercise in the muscles, was not augmented in the muscles of runner mice carrying the BDNF genetic variant.
“Our results, showing a lack of response to physical exercise treatment in BDNF Val66Met mutant mice, not only confirm the important role of BDNF, but also highlight the importance of genetic factors in moderating the response to physical exercise, and how much genetic variations should be taken into consideration in clinical trials” say investigators.
NeuroscienceNews would like to thank Alessandro Ieraci of the University of Milan for submitting this research article directly to us for inclusion.
Source: Alessandro Ieraci – University of Milan
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Original Research: Abstract for “Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice” by Alessandro Ieraci, Alessandro I Madaio, Alessandra Mallei, Francis S Lee and Maurizio Popoli in Neuropsychopharmacology. Published online July 6 2016 doi:10.1038/npp.2016.120
Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice
Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNFVal/Val) and homozygous BDNF Val66Met (BDNFMet/Met) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNFVal/Val but not in BDNFMet/Met mice. Hippocampal neurogenesis was reduced in BDNFMet/Met mice compared with BDNFVal/Val mice. BDNFMet/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNFMet/Met mice. Exercise failed to enhance PGC-1α and FNDC5 mRNA levels in the BDNFMet/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise.
“Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice” by Alessandro Ieraci, Alessandro I Madaio, Alessandra Mallei, Francis S Lee and Maurizio Popoli in Neuropsychopharmacology. Published online July 6 2016 doi:10.1038/npp.2016.120