Can Exercise Make You Smarter, Happier, and Have More Neurons? A Hormetic Perspective

Exercise can make you smarter, happier and have more neurons depending on the dose (intensity) of the training program. It is well recognized that exercise protocols induce both positive and negative effects depending on the intensity of the exercise, among other key factors, a process described as a hormetic-like biphasic dose-response. However, no evidences have been reported till very recently about the biphasic response of some of the potential mediators of the exercise-induced actions. This hypothesis and theory will focus on the adult hippocampal neurogenesis (AHN) as a putative physical substrate for hormesis responses to exercise in the context of exercise-induced actions on cognition and mood, and on the molecular pathways which might potentially be mediating these actions.The authors acknowledge the support of CSIC (Spanish Council for Scientific Investigation) and the Ministerio de Economía y Competitividad, Spain (research grant reference BFU2013-48907-R).Peer reviewedPeer Reviewe

Gαi2+ vomeronasal neurons govern the initial outcome of an acute social competition

Pheromone detection by the vomeronasal organ (VNO) mediates important social behaviors across different species, including aggression and sexual behavior. However, the relationship between vomeronasal function and social hierarchy has not been analyzed reliably. We evaluated the role of pheromone detection by receptors expressed in the apical layer of the VNO such as vomeronasal type 1 receptors (V1R) in dominance behavior by using a conditional knockout mouse for G protein subunit Gαi2, which is essential for V1R signaling. We used the tube test as a model to analyze the within-a-cage hierarchy in male mice, but also as a paradigm of novel territorial competition in animals from different cages. In absence of prior social experience, Gαi2 deletion promotes winning a novel social competition with an unfamiliar control mouse but had no effect on an established hierarchy in cages with mixed genotypes, both Gαi2−/− and controls. To further dissect social behavior of Gαi2−/− mice, we performed a 3-chamber sociability assay and found that mutants had a slightly altered social investigation. Finally, gene expression analysis in the medial prefrontal cortex (mPFC) for a subset of genes previously linked to social status revealed no differences between group-housed Gαi2−/− and controls. Our results reveal a direct influence of pheromone detection on territorial dominance, indicating that olfactory communication involving apical VNO receptors like V1R is important for the outcome of an initial social competition between two unfamiliar male mice, whereas final social status acquired within a cage remains unaffected. These results support the idea that previous social context is relevant for the development of social hierarchy of a group. Overall, our data identify two context-dependent forms of dominance, acute and chronic, and that pheromone signaling through V1R receptors is involved in the first stages of a social competition but in the long term is not predictive for high social ranks on a hierarchy.Fil: Pallé, Anna. Consejo Superior de Investigaciones Científicas; EspañaFil: Montero, Marta. Consejo Superior de Investigaciones Científicas; EspañaFil: Fernendez, Silvia. Consejo Superior de Investigaciones Científicas; EspañaFil: Tezanos, Patricia. Consejo Superior de Investigaciones Científicas; EspañaFil: De las Heras, Juan. Consejo Superior de Investigaciones Científicas; EspañaFil: Luskey, Valerie. Consejo Superior de Investigaciones Científicas; EspañaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Zufall, Frank. Universitat Saarland; AlemaniaFil: Chamero, Pablo. Centre National de la Recherche Scientifique; FranciaFil: Trejo, José Luis. Consejo Superior de Investigaciones Científicas; Españ

The GAPS programme at TNG XLIX. TOI-5398, the youngest compact multi-planet system composed of an inner sub-Neptune and an outer warm Saturn

Short-period giant planets are frequently found to be solitary compared to other classes of exoplanets. Small inner companions to giant planets with $P \lesssim$ 15 days are known only in five compact systems: WASP-47, Kepler-730, WASP-132, TOI-1130, and TOI-2000. Here, we report the confirmation of TOI-5398, the youngest compact multi-planet system composed of a hot sub-Neptune (TOI-5398 c, $P_{\rm c}$ = 4.77271 days) orbiting interior to a short-period Saturn (TOI-5398 b, $P_{\rm b}$ = 10.590547 days) planet, both transiting around a 650 $\pm$ 150 Myr G-type star. As part of the GAPS Young Object project, we confirmed and characterised this compact system, measuring the radius and mass of both planets, thus constraining their bulk composition. Using multidimensional Gaussian processes, we simultaneously modelled stellar activity and planetary signals from TESS Sector 48 light curve and our HARPS-N radial velocity time series. We have confirmed the planetary nature of both planets, TOI-5398 b and TOI-5398 c, alongside a precise estimation of stellar parameters. Through the use of astrometric, photometric, and spectroscopic observations, our findings indicate that TOI-5398 is a young, active G dwarf star (650 $\pm$ 150 Myr), with a rotational period of $P_{\rm rot}$ = 7.34 days. The transit photometry and radial velocity measurements enabled us to measure both the radius and mass of planets b, $R_b = 10.30\pm0.40 R_{\oplus}$, $M_b = 58.7\pm5.7 M_{\oplus}$, and c, $R_c = 3.52 \pm 0.19 R_{\oplus}$, $M_c = 11.8\pm4.8 M_{\oplus}$. TESS observed TOI-5398 during sector 48 and no further observations are planned in the current Extended Mission, making our ground-based light curves crucial for ephemeris improvement. With a Transmission Spectroscopy Metric value of around 300, TOI-5398 b is the most amenable warm giant (10 < $P$ < 100 days) for JWST atmospheric characterisation.Comment: 29 pages, Paper accepted for publication in Astronomy & Astrophysic

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

The GAPS programme at TNG : XLIX. TOI-5398, the youngest compact multi-planet system composed of an inner sub-Neptune and an outer warm Saturn

Context. Short-period giant planets (P ≲ 10 days, Mp >0.1 MJ) are frequently found to be solitary compared to other classes of exo-planets. Small inner companions to giant planets with P ≲ 15 days are known only in five compact systems: WASP-47, Kepler-730, WASP-132, TOI-1130, and TOI-2000. Here, we report the confirmation of TOI-5398, the youngest known compact multi-planet system composed of a hot sub-Neptune (TOI-5398 c, Pc = 4.77271 days) orbiting interior to a short-period Saturn (TOI-5398 b, Pb = 10.590547 days) planet, both transiting around a 650 ± 150 Myr G-type star. Aims. As part of the Global Architecture of Planetary Systems (GAPS) Young Object project, we confirmed and characterised this compact system, measuring the radius and mass of both planets, thus constraining their bulk composition. Methods. Using multi-dimensional Gaussian processes, we simultaneously modelled stellar activity and planetary signals from the Transiting Exoplanet Survey Satellite (TESS) Sector 48 light curve and our High Accuracy Radial velocity Planet Searcher (HARPS-N) radial velocity (RV) time series. We confirmed the planetary nature of both planets, TOI-5398 b and TOI-5398 c, and obtained a precise estimation of their stellar parameters. Results. Through the use of astrometric, photometric, and spectroscopic observations, our findings indicate that TOI-5398 is a young, active G dwarf star (650 ± 150 Myr) with a rotational period of Prot = 7.34 days. The transit photometry and RV measurements enabled us to measure both the radius and mass of planets b, Rb = 10.30 ± 0.40 R⊕, Mb = 58.7 ± 5.7 M⊕, and c, Rc = 3.52 ± 0.19 R⊕, Mc = 11.8 ± 4.8 M⊕. TESS observed TOI-5398 during sector 48 and no further observations are planned in the current Extended Mission, making our ground-based light curves crucial for improvement of the ephemeris. With a transmission spectroscopy metric (TSM) value of around 300, TOI-5398 b is the most amenable warm giant (10 < P < 100 days) for JWST atmospheric characterisation

Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety-like behavior

Social hierarchies are crucial for a group's survival and can influence the way an individual behaves and relates to a given social context. The study of social rank has been classically based on ethological and observational paradigms, but it recently has taken advantage of the use of other approaches, such as the tube test that measures territorial dominance without the display of in situ aggression and is executable in group-living animals. However, little is known about how previous basal individual differences affect the development of dominance hierarchy measured in the tube test. We have analyzed in male mice body weight, locomotion, anxiety, and serum corticosterone both before and after the tube test, as well as adult hippocampal neurogenesis and transcriptome in the prefrontal cortex after the hierarchy had been established. We found differential gene expression between dominants and subordinates but no association between the other parameters and social status, neither pre- nor posttest. Our findings reveal that social rank in mice is stable along time and is not related to basal differences in stress, mood, or physical features. Lastly, real-time quantitative PCR analysis confirmed differential expression of vomeronasal and olfactory receptors in the cerebral cortex between dominant and subordinate individuals, suggesting that differential brain gene expression in the medial prefrontal cortex could potentially be used as a biomarker of social dominance.-Pallé, A., Zorzo, C., Luskey, V. E., McGreevy, K. R., Fernández, S., Trejo, J. L. Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety-like behavior.The authors are grateful to María de Ceballos [Cajal Institute, Consejo Superior de Investigaciones Científicas (CSIC)] for useful advice, Laude Garmendia (Animal House at the Cajal Institute) for unpayable help and advice, the Image Analysis Unit of the Cajal Institute, and to all members of the Centro Nacional de Biotecnología (CNB) Genome Analysis Unit. This work was supported by project grants from the Spanish Ministry of Economy and Competitiveness (BFU2013-48907-R and BFU2016-77162-R to J.L.T.). A.P. was funded by a Formación Personal Investigador (FPI) grant, and K.R.M. was funded by a contract associated with the project grants to J.L.T. mentioned above. The authors declare no conflicts of interest

Neuronal tetraploidization in the cerebral cortex correlates with reduced cognition in mice and precedes and recapitulates Alzheimer's-associated neuropathology

A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT) occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT in the normal brain remains unexplored. Here we show that age-associated dnNT occurs in both superficial and deep layers of the cerebral cortex of adult mice, a process that is blocked in the absence of E2F1, a known regulator of cell cycle progression. This blockage correlates with improved cognition despite compromised neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1 gene. We also show that the human cerebral cortex contains tetraploid neurons. In normal humans, age-associated dnNT specifically occurs in the entorhinal cortex whereas, in Alzheimer, dnNT also affects association cortices prior to neurofibrillary tangle formation. Alzheimer-associated dnNT is likely potentiated by altered amyloid precursor protein (APP) processing as it is enhanced in the cerebral cortex of young APPswe/PS1deltaE9 mice, long before the first amyloid plaques are visible in their brains. In contrast to age-associated dnNT, enhanced dnNT in APPswe/PS1deltaE9 mice mostly affects the superficial cortical layers. The correlation of dnNT with reduced cognition in mice and its spatiotemporal course, preceding and recapitulating Alzheimer-associated neuropathology, makes this process a potential target for intervention in Alzheimer's disease.This work was supported by the Ministerio de Economía y Competitividad [grant numbers SAF2012-38316 (J. M. F.), SAF2015-68488-R (J. M. F.), BFU2013-48907-R (J. L. T.)]; and an R&D contract with Tetraneuron S. L. (J. M. F.).Peer reviewe

Intergenerational transmission of the positive effects of physical exercise on brain and cognition

Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.We thank Cesar Cobaleda [Centre of Molecular Biology Severo Ochoa (CBMSO), Spanish National Research Council/Autonomous University of Madrid (CSIC/UAM), Madrid, Spain] and Alberto González-de la Vega (MegaLab, Madrid, Spain) for expert assistance and advice of the RNAseq, DAVID, and GSEA analysis; María Llorens-Martín (CBMSO, CSIC/UAM, Madrid, Spain) for useful discussions; Silvia Fernández (Cellular and Molecular Biology Unit, Cajal Institute, Madrid, Spain) and Laude Garmendia (Animal House, Cajal Institute, Madrid, Spain) for volunteer help and advice; the Image Analysis Unit of the Cajal Institute; Carmen Sandi (Brain Mind Institute, Lausanne, Switzerland) for helpful and useful advice and assistance; and all members of the National Centre for Biotechnology Mouse Embryo Cryopreservation Facility— María Jesús del Hierro, Marta Castrillo, and Lluís Montoliu—for their huge efforts and impressive involvement in the IVF experiments. This work was supported by the Spanish Ministry of Economy and Competitiveness Project Grants BFU2013-48907-R and BFU2016-77162-R (to J.L.T.), SAF2016-78845-R (to S.R.F.), RYC-2012-10193 and AGL2014-85739-R (to P.B.Á.), CP14/00105 and PI15/00134 (to A.M.-M.); by the Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness; and by the European Regional Development Fund Grant PT17/0009/0019 (to A.E.-C). Á.F.-L. was funded by a CSIC JAE-Doc Programme grant and VPlan Propio US-Acceso Grant, I.L.-T. was funded by a predoctoral fellowship (FPI) grant, and K.R.M. was funded by a contract associated with the above-mentioned project grants awarded to J.L.T