Recovery of hippocampal functions and modulation of muscarinic response by electroacupuncture in young diabetic rats

The muscarinic receptor response to acetylcholine regulates the hippocampal-related learning, memory, neural plasticity and the production and processing of the pro-nerve growth factor (proNGF) by hippocampal cells. The development and progression of diabetes generate a mild cognitive impairment reducing the functions of the septo-hippocampal cholinergic circuitry, depressing neural plasticity and inducing proNGF accumulation in the brain. Here we demonstrate, in a rat model of early type-1 diabetes, that a physical therapy, the electroacupuncture, counteracts the diabetes-induced deleterious effects on hippocampal physiology by ameliorating hippocampal-related memory functions; recovering the impaired long-term potentiation at the dentate gyrus (DG-LTP) and the lowered expression of the vesicular glutamate transporter 1; normalizing the activity-dependent release of proNGF in diabetic rat hippocampus. Electroacupuncture exerted its therapeutic effects by regulating the expression and activity of M1- and M2-acetylcholine muscarinic receptors subtypes in the dentate gyrus of hippocampus. Our results suggest that a physical therapy based on repetitive sensory stimulation could promote hippocampal neural activity, neuronal metabolism and functions, and conceivably improve the diabetes-induced cognitive impairment. Our data can support the setup of therapeutic protocols based on a better integration between physical therapies and pharmacology for the cure of diabetes-associated neurodegeneration and possibly for Alzheimer's disease

La facu, un camino posible

Desde principios de este año, el Observatorio de Jóvenes, Comunicación y Medios implementa el proyecto de Voluntariado Universitario "De la escuela a la Facu, un camino posible", dirigido por la Dra. Florencia Saintout y coordinado por la Prof. Karina Vitaller. La escuela y la universidad, como partes fundamentales del proyecto de la modernidad, se encuentran en una encrucijada. Trabajar con jóvenes que se educaron en esas instituciones que se iban deteriorando durante la década del 90 implica rescatar el sentido de la educación pública como proyecto igualitario. Este proyecto de voluntariado en el cual participamos propone vivenciar la experiencia de ser un estudiante universitario para que estos jóvenes, en condiciones de vulnerabilidad social puedan ver a la Universidad dentro del horizonte de su futuro como un lugar capaz de incluirlos. Para nosotros, el proyecto representa un aporte valioso para la sociedad; no se trata de que todos los chicos vayan a la Universidad, pero sí de que sientan que pueden si así lo desean, que es su derecho también. Que la facu es un "camino posible".Facultad de Periodismo y Comunicación Socia

La facu, un camino posible

Desde principios de este año, el Observatorio de Jóvenes, Comunicación y Medios implementa el proyecto de Voluntariado Universitario "De la escuela a la Facu, un camino posible", dirigido por la Dra. Florencia Saintout y coordinado por la Prof. Karina Vitaller. La escuela y la universidad, como partes fundamentales del proyecto de la modernidad, se encuentran en una encrucijada. Trabajar con jóvenes que se educaron en esas instituciones que se iban deteriorando durante la década del 90 implica rescatar el sentido de la educación pública como proyecto igualitario. Este proyecto de voluntariado en el cual participamos propone vivenciar la experiencia de ser un estudiante universitario para que estos jóvenes, en condiciones de vulnerabilidad social puedan ver a la Universidad dentro del horizonte de su futuro como un lugar capaz de incluirlos. Para nosotros, el proyecto representa un aporte valioso para la sociedad; no se trata de que todos los chicos vayan a la Universidad, pero sí de que sientan que pueden si así lo desean, que es su derecho también. Que la facu es un "camino posible".Facultad de Periodismo y Comunicación Socia

Barreras que dificultan la procuracion de organos y tejidos para trasplantes en la provincia de Misiones. 16H221

La temática transplantológica ha tenido avances sin precedentes en la ciencia médica, y la medicina de nuestro país ha acompañado de cerca esta evolución del conocimiento, al punto de colocar a nuestros especialistas en el tema y al INCUCAI en una posición de liderazgo en Latinoamérica. Así, el implante de órganos, tejidos y células se ha vuelto una práctica cada vez más frecuente en nuestro sistema de salud. Además, debido a la eficacia de sus resultados, se transforma día a día en una terapéutica cuya indicación se multiplica para todos los casos. Sin embargo, lejos está el sistema de salud de la Argentina, y especialmente el de las Provincias, de poder convertir a estos progresos científicos en una práctica médica masiva, al alcance de todos aquellos que la necesitan, en tiempos razonables de acceso. Entre otras razones, por la insuficiente cantidad de donaciones de órganos y tejidos que se materializan. La enorme brecha que existe actualmente entre el número de personas diagnosticadas para un trasplante (Lista de Espera) y el de las donaciones que efectivamente se concretan (Procuración) se ha convertido en el principal problema a resolver por el sistema sanitario. Los siguientes datos proporcionados por el SINTRA (Sistema Nacional de Información de Procuración y Trasplante) son indicativos de la situación a nivel de todo el País y en nuestra Provincia (datos referidos a órganos y tejidos)

Herpes simplex virus-1 in the brain. The dark side of a sneaky infection

Herpes simplex virus-1 (HSV-1) establishes latency preferentially in sensory neurons of peripheral ganglia. A variety of stresses can induce recurrent reactivations of the virus, which spreads and then actively replicates to the site of primary infection (usually the lips or eyes). Viral particles produced following reactivation can also reach the brain, causing a rare but severe form of diffuse acute infection, namely herpes simplex encephalitis. Most of the time, this infection is clinically asymptomatic. However, it was recently correlated with the production and accumulation of neuropathological biomarkers of Alzheimer's disease. In this review we discuss the different cellular and molecular mechanisms underlying the acute and long-term damage caused by HSV-1 infection in the brain

Recurrent Herpes simplex virus type 1 (HSV-1) infection modulates neuronal aging marks in in vitro and In vivo models

Herpes simplex virus 1 (HSV-1) is a widespread neurotropic virus establishing a life-long latent infection in neurons with periodic reactivations. Recent studies linked HSV-1 to neurodegenerative processes related to age-related disorders such as Alzheimer’s disease. Here, we explored whether recurrent HSV-1 infection might accelerate aging in neurons, focusing on peculiar marks of aged cells, such as the increase in histone H4 lysine (K) 16 acetylation (ac) (H4K16ac); the decrease of H3K56ac, and the modified expression of Sin3/HDAC1 and HIRA proteins. By exploiting both in vitro and in vivo models of recurrent HSV-1 infection, we found a significant increase in H4K16ac, Sin3, and HDAC1 levels, suggesting that the neuronal response to virus latency and reactivation includes the upregulation of these aging markers. On the contrary, we found a significant decrease in H3K56ac that was specifically linked to viral reactivation and apparently not related to aging-related markers. A complex modulation of HIRA expression and localization was found in the brain from HSV-1 infected mice suggesting a specific role of this protein in viral latency and reactivation. Overall, our results pointed out novel molecular mechanisms through which recurrent HSV-1 infection may affect neuronal aging, likely contributing to neurodegeneration

Electroacupuncture in rats normalizes the diabetes-induced alterations in the septo-hippocampal cholinergic system

Diabetes induces early sufferance in the cholinergic septo-hippocampal system, characterized by deficits in learning andmemory, reduced hippocampal plasticity and abnormal pro-nerve growth factor (proNGF) release from hippocampal cells, all linked to dysfunctions in the muscarinic cholinergic modulation of hippocampal physiology. These alterations are associated with dysregulation of several cholinergic markers, such as the NGF receptor system and the acetylcholine biosynthetic enzyme choline-acetyl transferase (ChAT), in the medial septum and its target, the hippocampus. Controlled and repeated sensory stimulation by electroacupuncture has been proven effective in counteracting the consequences of diabetes on cholinergic system physiology in the brain. Here, we used a wellestablished Type 1 diabetes model, obtained by injecting young adult male rats with streptozotocin, to induce sufferance in the septo-hippocampal system.We then evaluated the effects of a 3-week treatmentwith low-frequency electroacupuncture on: (a) the expression and protein distribution of proNGF in the hippocampus, (b) the tissue distribution and content of NGF receptors in the medial septum, (c) the neuronal cholinergic and glial phenotype in the septo-hippocampal circuitry. Twice-a-week treatment with low-frequency electroacupuncture normalized, in both hippocampus and medial septum, the ratio between the neurotrophic NGF and its neurotoxic counterpart, the precursor proNGF. Electroacupuncture regulated the balance between the two major proNGF variants (proNGF-A and proNGF-B) at both gene expression and protein synthesis levels. In addition, electroacupuncture recovered to basal level the pro-neurotrophic NGF receptor tropomyosin receptor kinase-A content, down-regulated in medial septum cholinergic neurons by diabetes. Electroacupuncture also regulated ChAT content in medial septum neurons and its anterograde transport toward the hippocampus. Our data indicate that repeated sensory stimulation can positively affect brain circuits involved in learning and memory, reverting early impairment induced by diabetes development. Electroacupuncture could exert its effects on the septo-hippocampal cholinergic neurotransmission in diabetic rats, not only by rescuing the hippocampal muscarinic responsivity, as previously described, but also normalizing acetylcholine biosynthesis and NGFmetabolismin the hippocampus

Effects of intranasally-delivered pro-nerve growth factors on the septo-hippocampal system in healthy and diabetic rats

Pro-nerve growth factor (proNGF) is the predominant form of NGF in the brain and its levels increase in neurodegenerative diseases. The balance between NGF receptors may explain the contradictory biological activities of proNGF. However, the specific role of the two main proNGF variants is mostly unexplored. proNGF-A is prevalently expressed in healthy brain, while proNGF-B content increases in the neuro-degenerating brain. Recently we have investigated in vitro the biological action of native mouse proNGF variants. To gain further insights into the specific functions of the two proNGFs, here we intranasally delivered mouse-derived proNGF-A and proNGF-B to the brain parenchyma of healthy and diabetic rats, the latter characterized by dysfunction in spatial learning and memory, in the septo-hippocampal circuitry and by relative increase in proNGF-B hippocampal levels. Exogenous proNGF-B induces depression of hippocampal DG-LTP and impairment of hippocampal neurogenesis in healthy animals, with concomitant decrease in basal forebrain cholinergic neurons and cholinergic fibers projecting to the hippocampus. proNGF-A, while ineffective in healthy animals, rescues the diabetes- induced impairment in DG-LTP and hippocampal neurogenesis, promoting the concomitant recovery of the basal forebrain cholinergic phenotype. Our experimental evidences suggest that the balance between different proNGFs may influence the development and progression of neurodegenerative diseases

Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine N-Oxides with Anti-Influenza A Virus Activity

Belladine N-oxides active against influenza A virus have been synthetized by a novel laccase-catalyzed 1,4-dioxane-mediated oxidation of aromatic and side-chain modified belladine derivatives. Electron paramagnetic resonance (EPR) analysis confirmed the role of 1,4-dioxane as a co-oxidant. The reaction was chemo-selective, showing a high functional-group compatibility. The novel belladine N-oxides were active against influenza A virus, involving the early stage of the virus replication life cycle

The inhibition of DNA viruses by the amphibian antimicrobial peptide temporin G. A virological study addressing HSV-1 and JPCyV

Herpes simplex virus type-1 (HSV-1) and John Cunningham polyomavirus (JCPyV) are widely distributed DNA viruses causing mainly asymptomatic infection, but also mild to very severe diseases, especially when these viruses reach the brain. Some drugs have been developed to inhibit HSV-1 replication in host cells, but their prolonged use may induce resistance phenomena. In contrast, to date, there is no cure for JCPyV. The search for alternative drugs that can reduce viral infections without undermining the host cell is moving toward antimicrobial peptides (AMPs) of natural occurrence. These include amphibian AMPs belonging to the temporin family. Herein, we focus on temporin G (TG), showing that it strongly affects HSV-1 replication by acting either during the earliest stages of its life cycle or directly on the virion. Computational studies have revealed the ability of TG to interact with HSV-1 glycoprotein B. We also found that TG reduced JCPyV infection, probably affecting both the earliest phases of its life cycle and the viral particle, likely through an interaction with the viral capsid protein VP1. Overall, our results are promising for the development of short naturally occurring peptides as antiviral agents used to counteract diseases related to HSV-1 and JCPyV