Inhibition of IL-34 Unveils Tissue-Selectivity and Is Sufficient to Reduce Microglial Proliferation in a Model of Chronic Neurodegeneration.

The proliferation and activation of microglia, the resident macrophages in the brain, is a hallmark of many neurodegenerative diseases such as Alzheimer's disease (AD) and prion disease. Colony stimulating factor 1 receptor (CSF1R) is critically involved in regulating microglial proliferation, and CSF1R blocking strategies have been recently used to modulate microglia in neurodegenerative diseases. However, CSF1R is broadly expressed by many cell types and the impact of its inhibition on the innate immune system is still unclear. CSF1R can be activated by two independent ligands, CSF-1 and interleukin 34 (IL-34). Recently, it has been reported that microglia development and maintenance depend on IL-34 signaling. In this study, we evaluate the inhibition of IL-34 as a novel strategy to reduce microglial proliferation in the ME7 model of prion disease. Selective inhibition of IL-34 showed no effects on peripheral macrophage populations in healthy mice, avoiding the side effects observed after CSF1R inhibition on the systemic compartment. However, we observed a reduction in microglial proliferation after IL-34 inhibition in prion-diseased mice, indicating that microglia could be more specifically targeted by reducing IL-34. Overall, our results highlight the challenges of targeting the CSF1R/IL34 axis in the systemic and central compartments, important for framing any therapeutic effort to tackle microglia/macrophage numbers during brain disease.

Efecto de la Nicotina en un Modelo de Activación Dopaminérgica en Timing: Hacia un Modelo en Esquizofrenia / Nicotine Effect on a Model of Hyperactivation of the Dopaminergic System using a Temporal Bisection Task: Towards a Model in Schizophrenia

Resumen: La esquizofrenia es un trastorno que implica múltiples anomalías bioquímicas. Los pacientes con esquizofrenia tienen una prevalencia muy alta de tabaquismo, que se ha relacionado con el hecho de que la nicotina tiene importantes interacciones con la dopamina, siendo teóricamente capaz de reducir algunos de los síntomas positivos, negativos y cognitivos de la esquizofrenia. Sin embargo, existe controversia respecto al papel de la nicotina en la sintomatologia de los pacientes con esquizofrenia fumadores. El objetivo de la presente investigación fue evaluar el efecto de la administración de nicotina en un modelo de hiperactivación del sistema dopaminérgico, mediante una tarea de estimación temporal en animales del laboratorio. Los resultados sugieren una recuperación de las habilidades cognitivas, sin embargo el efecto procognitivo de la nicotina depende de una gran variedad de factores, incluyendo los sistemas neurales subyacentes a las tareas usadas y su interacción con otros fármacos y sistemas. Se propone que la evaluación del procesamiento de la información temporal puede servir como una herramienta en la comprensión y evaluación de los déficits cognitivos de la esquizofrenia.

Abstract: Schizophrenia is a disorder that involves multiple biochemical abnormalities. Patients with schizophrenia have a high prevalence of smoking, which has been linked with the fact that nicotine has significant interactions with dopamine, theoretically being able to reduce some of the positive, negative and cognitive symptoms of schizophrenia. However, there is controversy about the role of nicotine on symptoms of patients with schizophrenia who smoke. The objective of this research was to evaluate the effect of nicotine administration in a model of hyperactivation of the dopaminergic system using a temporal bisection task. The results suggest a recovery of cognitive skills, but the procognitive effect of nicotine depends on a variety of factors, including the underlying neural systems of the tasks and its interaction with other drugs and systems. It is proposed that the evaluation of the temporal processing of information could be a tool in the understanding and assessment of cognitive deficits of schizophrenia.

El Amaranto como Fuente de Reforzamiento: Un Estudio con Roedores / Amaranth as Reinforcement Source: A Rodent Study

Resumen: El presente estudio evalúa el amaranto como una alternativa a los reforzadores que se utilizan en la actualidad en los laboratorios experimentales con roedores. Se compararon diversos elementos como la preferencia de consumo, la motivación y el valor reforzante entre tres tipos de alimentos (dos tipos de pellets y amaranto) mediante cuatro experimentos con laberinto radial y consumo libre en 11 ratas de la cepa Wistar. Los resultados muestran que el amaranto tiene un alto valor reforzante ya que, se observó preferencia por su consumo comparado con los demás alimentos. Se propone al amaranto como una buena alternativa para usarse como reforzador con varias ventajas como la preferencia de consumo, su valor reforzante, su fácil accesibilidad en el país y que es más económico que los pellets importados.

Abstract: This study evaluates amaranth as an alternative to reinforcers which are currently used in experimental laboratories with rodents. We compared some elements such as consumer preference, motivation and reinforcing value of three types of food (two types of pellets and amaranth) through four experiments with free radial maze and free consumption in 11 Wistar rats. The results show that amaranth has a high reinforcing value. Also, there was a preference for amaranth consumption compared with the other two reinforcers. Amaranth is proposed as a good alternative for use as a reinforcer with several advantages such as consumer preference, its reinforcing value, accessibility in the country and that it is cheaper than the usual pellets.