TY - JOUR
T1 - Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex
AU - Sette, Claudio
AU - Innocenzi, Elisa
AU - Cariati, Ida
AU - De Domenico, Emanuela
AU - Tiberi, Erika
AU - D’Arcangelo, Giovanna
AU - Verdile, Veronica
AU - Paronetto, Maria Paola
AU - Tancredi, Virginia
AU - Barchi, Marco
AU - Rossi, Pellegrino
AU - Grimaldi, Paola
PY - 2021
Y1 - 2021
N2 - Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving
plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still
limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important
in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and
NRXN3) have been identified, each encoding for and neurexins, from two independent promoters.
Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that
bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength,
and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program
on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We
showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in and isoforms, inducing
a switch from exon-excluded isoforms (SS4) to exon-included isoforms (SS4+) in FC but not in
hippocampus. Additionally, we showed that the same AE program enhanced the expression level
of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings
demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic
plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show
molecular changes.
AB - Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving
plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still
limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important
in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and
NRXN3) have been identified, each encoding for and neurexins, from two independent promoters.
Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that
bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength,
and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program
on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We
showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in and isoforms, inducing
a switch from exon-excluded isoforms (SS4) to exon-included isoforms (SS4+) in FC but not in
hippocampus. Additionally, we showed that the same AE program enhanced the expression level
of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings
demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic
plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show
molecular changes.
KW - alternative splicing
KW - exercise
KW - frontal cortex
KW - hippocampus
KW - neurexins
KW - synapsis
KW - alternative splicing
KW - exercise
KW - frontal cortex
KW - hippocampus
KW - neurexins
KW - synapsis
UR - http://hdl.handle.net/10807/189621
U2 - 10.3390/jfmk6020048
DO - 10.3390/jfmk6020048
M3 - Article
VL - 2021
SP - 1
EP - 15
JO - Journal of Functional Morphology and Kinesiology
JF - Journal of Functional Morphology and Kinesiology
SN - 2411-5142
ER -