Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

Rat spermatogenesis damage in intermittent hypobaric hypoxia and the protective role of melatonin. II: testicular parameters.

In the heart, the main pathway for calcium influx is mediated by L-type calcium channels, a multi-subunit complex composed of the pore-forming subunit CaV1.2 and the auxiliary subunits CaVα2δ1 and CaVβ2. To date, five distinct CaVβ2 transcriptional start site (TSS) variants (CaVβ2a-e) varying only in the composition and length of the N-terminal domain have been described, each of them granting distinct biophysical properties to the L-type current. However, the physiological role of these variants in Ca(2+) handling in the native tissue has not been explored. Our results show that four of these variants are present in neonatal rat cardiomyocytes. The contribution of those CaVβ2 TSS variants on endogenous L-type current and Ca(2+) handling was explored by adenoviral-mediated overexpression of each CaVβ2 variant in cultured newborn rat cardiomyocytes. As expected, all CaVβ2 TSS variants increased L-type current density and produced distinctive changes on L-type calcium channel (LTCC) current activation and inactivation kinetics. The characteristics of the induced calcium transients were dependent on the TSS variant overexpressed. Moreover, the amplitude of the calcium transients varied depending on the subunit involved, being higher in cardiomyocytes transduced with CaVβ2a and smaller in CaVβ2d. Interestingly, the contribution of Ca(2+) influx and Ca(2+) release on total calcium transients, as well as the sarcoplasmic calcium content, was found to be TSS-variant-dependent. Remarkably, determination of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) messenger RNA (mRNA) abundance and cell size change indicates that CaVβ2 TSS variants modulate the cardiomyocyte hypertrophic state. In summary, we demonstrate that expression of individual CaVβ2 TSS variants regulates calcium handling in cardiomyocytes and, consequently, has significant repercussion in the development of hypertrophy.

RESUMEN: Hay una sorprendente relación entre el ambiente y adaptaciones de la conducta reproductiva, muy evidente en los reproductores estacionales que pueden reproducirse en días cortos o largos, de acuerdo a factores proximales, especialmente el fotoperiodo luminoso que provoca cambios fotoneuroendocrinos. Estos, involucran fotoreceptores, un reloj biológico y el aparato neuroendocrino. Las gonadotrofinas (GT), el desarrollo gonadal, la retroalimentación negativa de las GT por los esteroides sexuales, la intervención de las fibras retino-hipotalámico y los núcleos supraquiasmáticos así como la secreción de melatonina, intervienen en esta regulación. El pulso generador del hipotálamo (eminencia media) es importante en el control de la adenohipófisis respecto de la secreción de LH y FSH. En el testículo, las endocrinocitos intersticiales (de Leydig) (que secretan testosterona y también estrógenos), establecen un asa de retroalimentación con la adenohipófisis y el hipotálamo en un circuito de asa larga, corta y ultracorta, donde neuronas neuroendocrinas tienen un rol importante. Los sustentocitos (células de Sertoli) (intratubulares) son importantes por su rol mecánico, trófico y metabólico respecto a las células germinales y la secreción de activina e inhibina, que provoca o inhibe la secreción de FSH respectivamente. Los sustentocitos también secretan muchas proteínas específicas entre las cuales se encuentra la proteína que liga andrógenos (ABP), importante porque concentra 100 veces la testosterona en el parénquima testicular. La secreción tónica, por pulsos de GT, especialmente LH, es debida a actividad hipotalámica a través del control de generación de estos pulsos que se inicia en la pubertad. La reproducción en el potro y el toro se presentan como ejemplos. PALABRAS CLAVE: Reproducción estacional; eje Hipotálamo-Hipófisis-Testículo; Neuroendocrinología y reproducción; Características reproductivas del potro y el toro.

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