Short-Term, Voluntary Exercise Affects Morpho-Functional Maturation of Adult-Generated Neurons in Rat Hippocampus

none5noPhysical exercise is a well-proven neurogenic stimulus, promoting neuronal progenitor proliferation and affecting newborn cell survival. Besides, it has beneficial effects on brain health and cognition. Previously, we found that three days of physical activity in a very precocious period of adult-generated granule cell life is able to antedate the appearance of the first GABAergic synaptic contacts and increase T-type Ca2+ channel expression. Considering the role of GABA and Ca2+ in fostering neuronal maturation, in this study, we used short-term, voluntary exercise on a running wheel to investigate if it is able to induce long-term morphological and synaptic changes in newborn neurons. Using adult male rats, we found that: (i) three days of voluntary physical exercise can definitively influence the morpho-functional maturation process of newborn granule neurons when applied very early during their development; (ii) a significant percentage of new neurons show more mature morphological characteristics far from the end of exercise protocol; (iii) the long-term morphological effects result in enhanced synaptic plasticity. Present findings demonstrate that the morpho-functional changes induced by exercise on very immature adult-generated neurons are permanent, affecting the neuron maturation and integration in hippocampal circuitry. Our data contribute to underpinning the beneficial potential of physical activity on brain health, also performed for short times.Davide Lattanzi, David Savelli, Marica Pagliarini, Riccardo Cuppini, Patrizia AmbroginiLattanzi, Davide; Savelli, David; Pagliarini, Marica; Cuppini, Riccardo; Ambrogini, Patrizi

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases