Influence of the NR3A subunit on NMDA receptor functions

Various combinations of subunits assemble to form the NMDA-type glutamate receptor (NMDAR), generating diversity in its functions. Here we review roles of the unique NMDAR subunit, NR3A, which acts in a dominant-negative manner to suppress receptor activity. NR3A-containing NMDARs display striking regional and temporal expression specificity, and, unlike most other NMDAR subtypes, they have a low conductance, are only modestly permeable to Ca2+, and pass current at hyperpolarized potentials in the presence of magnesium. While glutamate activates triheteromeric NMDARs composed of NR1/NR2/NR3A subunits, glycine is sufficient to activate diheteromeric NR1/NR3A-containing receptors. NR3A dysfunction may contribute to neurological disorders involving NMDARs, and the subunit offers an attractive therapeutic target given its distinct pharmacological and structural properties

Miocene Climatic Optimum fungal record and plant-based CREST climatic reconstruction from southern McMurdo Sound, Antarctica

Deep-time palynological studies are necessary to evaluate plant and fungal distribution under warmer-than-present scenarios such as those of the Middle Miocene. Previous palynological studies from southern McMurdo Sound, Antarctica (SMS), have provided unique documentation for Neogene environments in the Ross Sea region during a time of pronounced global warming. The present study builds on these studies and provides a new climate reconstruction using the previously published SMS pollen and plant spore data. Additionally, 44 SMS samples were reanalyzed with a focus on the fungal fraction of the section to evaluate the fungal distribution under warmer than present conditions. The probability-based climate reconstruction technique (CREST) was applied to provide a new plant-based representation of regional paleoclimate for this Miocene Climatic Optimum (MCO) locality. CREST reconstructs a paleoclimate that is warmer and significantly wetter than present in SMS during the MCO, with mean annual precipitation reconstructed at 1147 mm yr−1 (95 % confidence range: 238–2611 mm yr−1) and a maximum mean annual temperature of 10.3 ∘C (95 % confidence range: 2.0–20.2 ∘C) for the warmest intervals of the MCO. The CREST reconstruction fits within the Cfb Köppen–Geiger climate class during the MCO of SMS. This new reconstruction agrees with previous reconstructions using various geochemical proxies. The fungal palynological analyses yielded surprising results, with only a single morphotype recovered, in low abundance, with concentrations ranging up to 199 fungi per gram of dried sediment. The taxa present belongs to the Apiosporaceae family and are known to be adapted to a wide range of climate and environmental conditions. As fungi are depauperate members of the SMS MCO palynofloras and because the one morphotype recovered is cosmopolitan, using the fungi record to confirm a narrow Köppen–Geiger climate class is impossible. Overall, the study demonstrates refinement of plant-based paleoclimatic reconstructions and sheds light on the limited presence of fungi during the MCO in Antarctica.</p

Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models

Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. Yet, it remains unclear how the HTT mutation affects NMDAR function, and direct evidence for a causative role is missing. Here we show that mutant HTT redirects an intracellular store of juvenile NMDARs containing GluN3A subunits to the surface of striatal neurons by sequestering and disrupting the subcellular localization of the endocytic adaptor PACSIN1, which is specific for GluN3A. Overexpressing GluN3A in wild-type mouse striatum mimicked the synapse loss observed in Huntington's disease mouse models, whereas genetic deletion of GluN3A prevented synapse degeneration, ameliorated motor and cognitive decline and reduced striatal atrophy and neuronal loss in the YAC128 Huntington's disease mouse model. Furthermore, GluN3A deletion corrected the abnormally enhanced NMDAR currents, which have been linked to cell death in Huntington's disease and other neurodegenerative conditions. Our findings reveal an early pathogenic role of GluN3A dysregulation in Huntington's disease and suggest that therapies targeting GluN3A or pathogenic HTT-PACSIN1 interactions might prevent or delay disease progression

First Record of Fungal Diversity in the Tropical and Warm-Temperate Middle Miocene Climate Optimum Forests of Eurasia

The middle Miocene Climate Optimum (MMCO) was the warmest interval of the last 23 million years and is one of the best analogs for proposed future climate change scenarios. Fungi play a key role in the terrestrial carbon cycle as dominant decomposers of plant debris, and through their interactions with plants and other organisms as symbionts, parasites, and endobionts. Thus, their study in the fossil record, especially during the MMCO, is essential to better understand biodiversity changes and terrestrial carbon cycle dynamics in past analogous environments, as well as to model future ecological and climatic scenarios. The fossil record also offers a unique long-term, large-scale dataset to evaluate fungal assemblage dynamics across long temporal and spatial scales, providing a better understanding of how ecological factors influenced assemblage development through time. In this study, we assessed the fungal diversity and community composition recorded in two geological sections from the middle Miocene from the coal mines of Thailand and Slovakia. We used presence-absence data to quantify the fungal diversity of each locality. Spores and other fungal remains were identified to modern taxa whenever possible; laboratory codes and fossil names were used when this correlation was not possible. This study represents the first of its kind for Thailand, and it expands existing work from Slovakia. Our results indicate a total of 281 morphotaxa. This work will allow us to use modern ecological data to make inferences about ecosystem characteristics and community dynamics for the studied regions. It opens new horizons for the study of past fungal diversity based on modern fungal ecological analyses. It also sheds light on how global variations in fungal species richness and community composition were affected by different climatic conditions and under rapid increases of temperature in the past to make inferences for the near climatic future

Nr3a-containing NMDA receptors promote neurotransmitter release and spike timing-dependent plasticity

Recent evidence suggests that presynaptic-acting NMDA receptors (preNMDARs) are important for neocortical synaptic transmission and plasticity. We found that unique properties of the Nr3a subunit enable preNMDARs to enhance spontaneous and evoked glutamate release and that Nr3a is required for spike timing–dependent long-term depression in the juvenile mouse visual cortex. In the mature cortex, Nr2b-containing preNMDARs enhanced neurotransmission in the absence of magnesium, indicating that presynaptic NMDARs may function under depolarizing conditions throughout life. Our findings indicate that Nr3a relieves preNMDARs from the dual-activation requirement of ligand-binding and depolarization; the developmental removal of Nr3a limits preNMDAR functionality by restoring this associative property

Mitochondrial Ca2+ Overload Underlies Aβ Oligomers Neurotoxicity Providing an Unexpected Mechanism of Neuroprotection by NSAIDs

Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD

Downregulation of NR3A-Containing NMDARs Is Required for Synapse Maturation and Memory Consolidation

NR3A is the only NMDA receptor (NMDAR) subunit that down-regulates sharply prior to the onset of sensitive periods for plasticity, yet the functional importance of this transient expression remains largely unknown. To investigate the possibility that removal/replacement of juvenile NR3A-containing NMDARs is involved in experience-driven synapse maturation, we used a reversible transgenic system that allowed persistent NR3A expression in the postnatal forebrain. We found that removal of NR3A is required to develop strong NMDAR currents, full expression of long-term synaptic plasticity, a mature synaptic organization characterized by more synapses and larger postsynaptic densities, and the ability to form long-term memories. Deficits associated with prolonged NR3A were reversible, as late-onset suppression of transgene expression rescued both the synaptic and memory impairments. Our results suggest that NR3A behaves as a molecular brake to prevent the premature strengthening and stabilization of excitatory synapses, and that NR3A removal might thereby initiate critical stages of synapse maturation during early postnatal neural development

Estudio del consumo latinoamericano de frutas y hortalizas locales "Km 0"

La Horticultura, con sus diferentes disciplinas (Horticultura/Olericultura, Fruticultura, Aromáticas-Medicinales y Floricultura), ha cobrado mayor relevancia, a partir de la pandemia por Covid-19, con una mayor valoración de los productos provenientes de cadenas cortas. El objetivo fue evaluar el grado de conocimiento, comportamiento y preferencias de los consumidores latinoamericanos, respecto de la inocuidad, calidad y origen de las frutas y hortalizas (FyH) de cercanía producidas y consumidas en un radio no mayor a 100 Km, diferenciadas con el logo “Km 0”. Se generó una encuesta on line (GoogleForms): Estudio sobre la producción y el consumo latinoamericano de frutas y hortalizas "Km 0",en el marco de vínculos interinstitucionales (UNCPBA, UNMDP, UNSL, UCA e INTA Área CERBAS, de Argentina; UdelaR, Uruguay; UNAL y UniSalle, Colombia; BUAP, México; UFRRJ, Brasil), del 09/03/2022 al 12/07/2022. Los principales temas fueron: Grado de conocimiento de la categoría FyH “Km 0”; Ventajas percibidas; Predisposición a consumirlas y a adquirirlas; Grado de valoración del etiquetado “Km 0”; y de Campañas de difusión; Lugares de compra y cambios desde la pandemia; Valoración de disponer de listados de productores locales de FyH “Km 0”; Conocimiento del lugar de producción, de las FyH y valoración del impulso a las producciones locales; Conocimiento de las BPA; Alimentos adquiridos y Valoración del origen de las FyH consumidas. Las encuestas respondidas fueron 1127. Se detectó desconocimiento de la categoría “Km 0” (60%), bajo consumo de FyH (17% consume 5 ≥ porciones/día) aunque una elevada valoración de FyH en la dieta (80%). Se evidenció la necesidad de capacitaciones y difusión permanente, de la producción y consumo de FyH inocuas y de calidad, en cantidad y diversidad. La pandemia resultó un punto de inflexión a partir del cual los consumidores tomaron conciencia de la importancia del origen de los productos consumidos, prefiriendo FyH locales.Fil: Castagnino, Ana Maria. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Universidad Católica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; ArgentinaFil: Díaz, K. E.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Marina, Javier Alejandro. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Fernándes, C.. Universidade Federal Rural Do Rio de Janeiro (ufrrj);Fil: Díaz, H. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Bazán, P.. Universidad Nacional de San Luis. Facultad de Ingeniería y Ciencias Agropecuarias; ArgentinaFil: Rogers, William John. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Rubel, Irene Albertina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Otaño, Ana Clara. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Fasciglione, Gabriela. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Marín Castro, M. A.. Benemérita Universidad Autónoma de Puebla; MéxicoFil: Reina, R.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Galizio, R.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Cendón, M. L.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Zanelli, G.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Miranda Lasprilla, D.. Universidad Nacional de Colombia. Sede Bogotá; ColombiaFil: Chaparro, G. M. P.. Universidad de la Salle;Fil: Pérez, E. R.. Universidad Católica Argentina; ArgentinaFil: Yommi, A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Bastien, E.. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentin

Estudio del consumo latinoamericano de frutas y hortalizas locales "Km 0"

La Horticultura, con sus diferentes disciplinas (Horticultura/Olericultura, Fruticultura, Aromáticas-Medicinales y Floricultura), ha cobrado mayor relevancia, a partir de la pandemia por Covid-19, con una mayor valoración de los productos provenientes de cadenas cortas. El objetivo fue evaluar el grado de conocimiento, comportamiento y preferencias de los consumidores latinoamericanos, respecto de la inocuidad, calidad y origen de las frutas y hortalizas (FyH) de cercanía producidas y consumidas en un radio no mayor a 100 Km, diferenciadas con el logo “Km 0”. Se generó una encuesta on line (GoogleForms): Estudio sobre la producción y el consumo latinoamericano de frutas y hortalizas "Km 0",en el marco de vínculos interinstitucionales (UNCPBA, UNMDP, UNSL, UCA e INTA Área CERBAS, de Argentina; UdelaR, Uruguay; UNAL y UniSalle, Colombia; BUAP, México; UFRRJ, Brasil), del 09/03/2022 al 12/07/2022. Los principales temas fueron: Grado de conocimiento de la categoría FyH “Km 0”; Ventajas percibidas; Predisposición a consumirlas y a adquirirlas; Grado de valoración del etiquetado “Km 0”; y de Campañas de difusión; Lugares de compra y cambios desde la pandemia; Valoración de disponer de listados de productores locales de FyH “Km 0”; Conocimiento del lugar de producción, de las FyH y valoración del impulso a las producciones locales; Conocimiento de las BPA; Alimentos adquiridos y Valoración del origen de las FyH consumidas. Las encuestas respondidas fueron 1127. Se detectó desconocimiento de la categoría “Km 0” (60%), bajo consumo de FyH (17% consume 5 ≥ porciones/día) aunque una elevada valoración de FyH en la dieta (80%). Se evidenció la necesidad de capacitaciones y difusión permanente, de la producción y consumo de FyH inocuas y de calidad, en cantidad y diversidad. La pandemia resultó un punto de inflexión a partir del cual los consumidores tomaron conciencia de la importancia del origen de los productos consumidos, prefiriendo FyH locales.Fil: Castagnino, Ana Maria. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Universidad Católica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; ArgentinaFil: Díaz, K. E.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Marina, Javier Alejandro. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Fernándes, C.. Universidade Federal Rural Do Rio de Janeiro (ufrrj);Fil: Díaz, H. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Bazán, P.. Universidad Nacional de San Luis. Facultad de Ingeniería y Ciencias Agropecuarias; ArgentinaFil: Rogers, William John. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Rubel, Irene Albertina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Otaño, Ana Clara. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Fasciglione, Gabriela. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Marín Castro, M. A.. Benemérita Universidad Autónoma de Puebla; MéxicoFil: Reina, R.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Galizio, R.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Cendón, M. L.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Zanelli, G.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Miranda Lasprilla, D.. Universidad Nacional de Colombia. Sede Bogotá; ColombiaFil: Chaparro, G. M. P.. Universidad de la Salle;Fil: Pérez, E. R.. Universidad Católica Argentina; ArgentinaFil: Yommi, A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Bastien, E.. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentin

Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration

Synapse loss is an early feature shared by many neurodegenerative diseases, and it represents the major correlate of cognitive impairment. Recent studies reveal that microglia and astrocytes play a major role in synapse elimination, contributing to network dysfunction associated with neurodegeneration. Excitatory and inhibitory activity can be affected by glia-mediated synapse loss, resulting in imbalanced synaptic transmission and subsequent synaptic dysfunction. Here, we review the recent literature on the contribution of glia to excitatory/inhibitory imbalance, in the context of the most common neurodegenerative disorders. A better understanding of the mechanisms underlying pathological synapse loss will be instrumental to design targeted therapeutic interventions, taking in account the emerging roles of microglia and astrocytes in synapse remodeling