Control de la neurotraducción hipotalámica por los neurotransmisores cerebrales : regulación de la somastostatina hipotalámica por las catecolaminas

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída en 1982.Fac. de Ciencias BiológicasTRUEProQuestpu

Control de la neurotraducción hipotalámica por los neurotransmisores cerebrales : regulación de la somastostatina hipotalámica por las catecolaminas

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída en 1982.Fac. de Ciencias BiológicasTRUEProQuestpu

Homeostasis cerebral e IGF-I

Aunque los IGFs, y mas concretamente el IGF-I son conocidos sobretodo por su implicación fundamental en el eje somato-trópico controlado por la hormona de crecimiento hipofisaria, en los últimos años se ha ido desvelando un papel también muy importante del IGF-I a nivel cerebral. Quizás lo más llamativo de este nuevo aspecto de la fisiología del IGF-I es que sea el IGF-I circulante, de procedencia mayoritariamente hepática, el que tenga un efecto neuroactivo. Si bien el cerebro adulto produce pequeñas cantidades de IGF-I, es el de origen periférico el que resulta esencial para un funcionamiento adecuado de este órgano. De hecho, el papel del IGF-I cerebral en la fisiología neural todavía no está claro, revelando su importancia al parecer sólo en condiciones de alteración de la homeostasis. Sin embargo, la ausencia de IGF-I circulante genera un enorme impacto neurológico, produciendo desordenes anatómicos, bioquímicos y conductuales. Quizás lo mas llamativo del IGF-I sérico sea su papel sobre funciones cerebrales superiores tales como el aprendizaje y la memoria. Esta conexión entre periferia y sistema nervioso central implica el paso del IGF-I circulante al cerebro a través de las barreras hemato-encefálicas, hecho conocido desde hace años pero aún no aceptado plenamente ya que se considera que estas barreras son impermeables a la mayor parte de las proteínas sanguíneas. El IGF-I es un cito-protector de amplio espectro, también en el cerebro. Es además esencial para el mantenimiento tisular, encargándose de mantener una población celular acorde a las demandas funcionales. Contribuye al soporte energético celular de dos maneras, manteniendo el árbol vascular cerebral y por lo tanto asegurando un aporte de oxígeno y nutrientes, y regulando el metabolismo celular como agente anabólico por excelencia. Además ejerce funciones mas específicas del tejido neural. En concreto regula la excitabilidad neural –modula una enorme diversidad de canales iónicos, y diversos sistemas de neurotransmisión. De esta forma contribuye directamente al mantenimiento de las funciones superiores cerebrales que se traducen en una influencia directa sobre las capacidades cognitivas. Pero si algo define la neurobiología de este factor tan pleiotrópico es su papel central en la homeostasis cerebral. Es por eso que cualquier enfermedad neurológica presenta alteraciones en el sistema IGF-I. En situaciones de alteración de la homeostasis siempre se da una respuesta reactiva no sólo del IGF-I, también de otros muchos factores neuroprotectores. Pero es el IGF-I el encargado de orquestar en gran medida la respuesta adaptativa. De esta manera el IGF-I se puede considerar un elemento maestro en la homeostasis cerebral.

Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury

Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I) in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. The protection mediated by IGF-I against oxidative stress (H 2O 2) in astrocytes is probably needed for these cells to provide adequate neuroprotection. Indeed, in astrocytes but not in neurons, IGF-I helps decrease the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H 2O 2 such as stem cell factor (SCF) to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging. © 2014 Genis L et al.This work was funded by grants of the Spanish Ministry of Science (SAF2010-17036) and Centro Investigacion Biomedica en red Enfermedades Neurodegenerativas (CIBERNED) to IT-A.Peer Reviewe

Electrical and chapacitive response of hydrogel solid-like electrolytes for supercapacitors

Flexible hydrogels are attracting significant interest as solid-like electrolytes for energy storage devices, especially for supercapacitors, because of their lightweight and anti-deformation features. Here, we present a comparative study of four ionic conductive hydrogels derived from biopolymers and doped with 0.1 M NaCl. More specifically, such hydrogels are constituted by κ-carrageenan (κC), carboxymethyl cellulose (CMC), poly-γ-glutamic acid (PGGA) or a phenylalanine-containing polyesteramide (PEA). After examining the morphology and the swelling ratio of the four hydrogels, which varies between 483% and 2356%, their electrical and capacitive behaviors were examined using electrochemical impedance spectroscopy. Measurements were conducted on devices where a hydrogel film was sandwiched between two identical poly(3,4-ethylenedioxythiophene) electrodes. The bulk conductivity of the prepared doped hydrogels is 76, 48, 36 and 34 mS/cm for PEA, PGGA, κC and CMC, respectively. Overall, the polyesteramide hydrogel exhibits the most adequate properties (i.e., low electrical resistance and high capacitance) to be used as semi-solid electrolyte for supercapacitors, which has been attributed to its distinctive structure based on the homogeneous and abundant distribution of both micro- and nanopores. Indeed, the morphology of the polyestermide hydrogel reduces the hydrogel resistance, enhances the transport of ions, and results in a better interfacial contact between the electrodes and solid electrolyte. The correlation between the supercapacitor performance and the hydrogel porous morphology is presented as an important design feature for the next generation of light and flexible energy storage devices for wearable electronics.Postprint (published version

Brain IGF-I regulates hippocampal neurogenesis, synaptic plasticity, and sexual dimorphic behaviour

Comunicación presentada a SSii 2022 Spanish Symposium on IGFs and Insulin 2022: Implications in Physiology and DiseaseInsulin-like growth factor-I (IGF-I) exerts multiple actions, regulating body growth, cell proliferation, adult neurogenesis, neuronal and glial differentiation, synaptic plasticity and behaviour, among other processes. Both circulating and locally synthesized IGF-I are active, although the role of IGF-I from different sources is poorly understood. We previously found that brain IGF-I plays a major role in promoting the correct generation, migration and maturation of neurons from neural stem cells during postnatal adult hippocampal neurogenesis (Nieto-Estévez et al., 2016), although electrophysiological or behavioural phenotypes were not investigated in that study. Here we show that the lack of brain IGF-I almost completely abrogates hippocampal LTP, as well as altering sex-dependent behaviour and causing major changes in the hippocampal proteome. We suggest that the disruptions to the hippocampal proteome of conditional knockout Igf-I mice may partially underlie the changes observed in synaptic plasticity and behaviour

Insulin-like growth factor I sensitization rejuvenates sleep patterns in old mice

Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys. Furthermore, IGF-I shapes sleep architecture by modulating the activity of mouse orexin neurons in the lateral hypothalamus (LH). We now report that both ECoG activation and excitation of orexin neurons by systemic IGF-I are abrogated in old mice. Moreover, orthodromical responses of LH neurons are facilitated by either systemic or local IGF-I in young mice, but not in old ones. As orexin neurons of old mice show dysregulated IGF-I receptor (IGF-IR) expression, suggesting disturbed IGF-I sensitivity, we treated old mice with AIK3a305, a novel IGF-IR sensitizer, and observed restored responses to IGF-I and rejuvenation of sleep patterns. Thus, disturbed sleep structure in aging mice may be related to impaired IGF-I signaling onto orexin neurons, reflecting a broader loss of IGF-I activity in the aged mouse brain.This work was funded by a grant from Ciberned and is part of the project SAF2016-76462 funded by MCIN/AEI/https://doi.org/10.13039/501100011033. J.A. ZegarraValdivia acknowledges the fnancial support of the National Council of Science, Technology and Technological Innovation (CONCYTEC, Perú) through the National Fund for Scientifc and Technological Development (FONDECYT, Perú). J. Fernandes received a post-doc fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP: # 2017/14742–0; # 2019/03368–5)

Aging and Brain Deterioration

Carlos Dotti and Vicente Rodríguez (coordinators).Advanced age significantly increases the risk of developing chronic diseases such as cancer, diabetes, cardiovascular, immune and mental disease. Regarding the latter, advanced age is a necessary factor for the development of non-hereditary forms of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Despite years of intense research, we still do not know how these diseases occur, this being one of the main reasons for the lack of adequate interventions to prevent or cure these pathologies. To overcome the current limitations in the field, we plan to: 1) generate basic knowledge on the mechanisms responsible for cognitive, behavioral, motor, metabolic and sociability disorders that occur with age, 2) define the mechanisms that determine individual susceptibility to neurodegeneration, 3) design and develop strategies to improve brain aging, and 4) explore social and environmental conditions of the older population to know their influence in brain degeneration. Individual, social and policy interventions must be considered for future research.Peer reviewe