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Resumen Introduccion El glioblastoma multiforme es el tumor cerebral primario mas comun y con el pronostico mas desfavorable del sistema nervioso central. A pesar de los numerosos estudios y avances en medicina, este sigue siendo letal, con una esperanza de vida promedio de 15 meses posteriores a la quimiorradioterapia. Desarrollo Recientemente, se han estudiado diversos factores asociados al diagnostico y el pronostico de pacientes con glioblastoma, como la localizacion tumoral, principalmente la zona subventricular; una de las areas neurogenicas mas activas del cerebro humano adulto. Los pacientes con glioblastoma asociados a esta zona en particular presentan generalmente una mayor agresividad, lo que resulta en un pronostico desfavorable y una menor esperanza de vida. Actualmente, se ha profundizado en el estudio de los microARN, los cuales reflejan patrones de expresion distintos en condiciones fisiologicas o fisiopatologicas. Esta reportado que los niveles de expresion de ciertos microARN, principalmente aquellos relacionados a procesos neurogenicos, se ven desregulados en eventos oncogenicos, favoreciendo asi la gliomagenesis y la agresividad tumoral. En la presente revision se discuten algunos de los microARN mas importantes implicados en procesos neurogenicos de la zona subventricular y su asociacion con la agresividad del glioblastoma. Conclusiones La regulacion y funcion de los microARN desempena un rol importante en el desarrollo y la progresion del glioblastoma; en consecuencia, la comprension de las alteraciones de los microARN implicados en la diferenciacion, asi como en la maduracion neural y glial, podrian ayudar a entender mejor las caracteristicas malignas del glioblastoma.

BackgroundCognition and brain function is critical through childhood and should be improved with balanced diets. Incorporating bioactive ingredients such as omega-3 polyunsaturated fatty acids (ω3 PUFAs) and probiotics into food formulations could be used as an approach to improve cognitive function. This study evaluated the effects on cognitive capacity of complementing rodent diets with chocolate, by itself and in combination with ω3 PUFAs from fish oil and probiotics.MethodsSpatial learning and memory in the rats were determined by the Barnes maze test in short- and long-term memory. Samples from the cecum were obtained to assess microbial counts (Lactobacillus, Bifidobacterium, Enterobacteriaceae, and total bacteria), and brains were recovered to analyze the neural morphology of the tissues. Also, glucose, brain weights, and epididymal tissue were analyzed.ResultsThe combination of chocolate with fish oil and probiotics improved the memory of rats compared to the result of each bioactive compound when evaluated separately. Treatments did not affect sugar level, epididymal adipose tissue, or brain weight. On the other hand, consuming probiotics alone or in combination with chocolate decreased Enterobacteria counts, while Lactobacillus and Bifidobacteria counts were not affected. Neural morphological analysis showed that combining chocolate with probiotics and ω3 PUFAs increased the number of neurons in the hippocampal CA1 and CA3 regions.ConclusionChocolate added with probiotics and ω3 PUFAs improved spatial memory and learning in the studied model.

Resumen: Introducción: La enfermedad renal crónica (ERC) puede provocar anemia e inducir afectaciones neurológicas. La eritropoyetina humana recombinante (rHuEPO) se utiliza en el tratamiento de la anemia en la ERC. Sin embargo, existe poca evidencia de los efectos de la rHuEPO sobre la conducta y las funciones cognitivas en la ERC. El objetivo de este estudio fue evaluar el efecto del tratamiento con rHuEPO sobre las funciones sensoriomotoras y cognitivas en un modelo de ERC. Métodos: Ratas macho de la cepa Wistar fueron asignadas a 4 grupos: control y ERC, con y sin tratamiento con rHuEPO (1.050 UI/kg de peso, una vez por semana durante 4 semanas). Las pruebas conductuales de laberinto acuático de Morris, campo abierto y cinta adhesiva se realizaron de manera simultánea a la inducción del daño renal y el tratamiento. Mientras que la determinación de marcadores de función renal y anemia se realizaron al término del estudio. Resultados: El tratamiento con rHuEPO redujo el daño en el riñón y corrigió la anemia en las ratas con ERC. En las pruebas conductuales, el tratamiento con rHuEPO redujo la disfunción sensoriomotora observada en los animales con ERC. Por otra parte, en los animales con ERC y tratamiento con rHuEPO resolvieron el laberinto en menor tiempo en comparación a los grupos control. Conclusiones: El tratamiento con rHuEPO reduce el daño en el riñón, corrige la anemia y reduce la disfunción sensoriomotora y cognitiva en los animales con ERC. Abstract: Introduction: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Methods: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Results: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. Conclusions: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Palabras clave: Enfermedad renal crónica, Función sensoriomotora, Deterioro cognitivo, Eritropoyetina, Keywords: Chronic kidney disease, Sensorimotor function, Cognitive impairment, Erythropoietin

Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination, these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs, as a result, the remyelination capacity of the CNS decreases over time. Several experimental studies have introduced OPCs to the brain via direct injection or intrathecal administration. In this study, we used the nose-to brain pathway to deliver oligodendrocyte lineage cells (human oligodendroglioma (HOG) cells), which behave similarly to OPCs in vitro. To this end, we administered GFP-labelled HOG cells intranasally to experimental animals, which were subsequently euthanised at 30 or 60 days. Our results show that the intranasal route is a viable route to the CNS and that HOG cells administered intranasally migrate preferentially to niches of OPCs (clusters created during embryonic development and adult life). Our study provides evidence, albeit limited, that HOG cells either form clusters or adhere to clusters of OPCs in the brains of experimental animals.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS.

In late December 2019, multiple atypical pneumonia cases resulted in severe acute respiratory syndrome caused by a pathogen identified as a novel coronavirus SARS-CoV-2. The most common coronavirus disease 2019 (COVID-19) symptoms are pneumonia, fever, dry cough, and fatigue. However, some neurological complications following SARS-CoV-2 infection include confusion, cerebrovascular diseases, ataxia, hypogeusia, hyposmia, neuralgia, and seizures. Indeed, a growing literature demonstrates that neurotropism is a common feature of coronaviruses; therefore, the infection mechanisms already described in other coronaviruses may also be applicable for SARS-CoV-2. Understanding the underlying pathogenetic mechanisms in the nervous system infection and the neurological involvement is essential to assess possible long-term neurological alteration of COVID-19. Here, we provide an overview of associated literature regarding possible routes of COVID-19 neuroinvasion, such as the trans-synapse-connected route in the olfactory pathway and peripheral nerve terminals and its neurological implications in the central nervous system.

Alzheimer's disease (AD) is a chronic brain disorder characterized by progressive intellectual decline and memory and neuronal loss, caused mainly by extracellular deposition of amyloid-β (Aβ) and intracellular accumulation of hyperphosphorylated tau protein, primarily in areas implicated in memory and learning as prefrontal cortex and hippocampus. There are two forms of AD, a late-onset form that affects people over 65 years old, and the early-onset form, which is hereditable and affect people at early ages ~45 years. To date, there is no cure for the disease; consequently, it is essential to develop new tools for the study of processes implicated in the disease. Currently, in vitro AD three-dimensional (3D) models using induced pluripotent stem cells (iPSC)-derived neurons have broadened the horizon for in vitro disease modeling and gained interest for mechanistic studies and preclinical drug discovery due to their potential advantages in providing a better physiologically relevant information and more predictive data for in vivo tests. Therefore, this study aimed to establish a 3D cell culture model of AD in vitro using iPSCs carrying the A246E mutation. We generated human iPSCs from fibroblasts from a patient with AD harboring the A246E mutation in the PSEN1 gene. Cell reprogramming was performed using lentiviral vectors with Yamanaka's factors (OSKM: Oct4, Sox2, Klf4, and c-Myc). The resulting iPSCs expressed pluripotency genes (such as Nanog and Oct4), alkaline phosphatase activity, and pluripotency stem cell marker expression, such as OCT4, SOX2, TRA-1-60, and SSEA4. iPSCs exhibited the ability to differentiate into neuronal lineage in a 3D environment through dual SMAD inhibition as confirmed by Nestin, MAP2, and Tuj1 neural marker expression. These iPSC-derived neurons harbored Aβ oligomers confirmed by Western Blot (WB) and immunostaining. With human iPSC-derived neurons able to produce Aβ oligomers, we established a novel human hydrogel-based 3D cell culture model that recapitulates Aβ aggregation without the need for mutation induction or synthetic Aβ exposure. This model will allow the study of processes implicated in disease spread throughout the brain, the screening of molecules or compounds with therapeutic potential, and the development of personalized therapeutic strategies.

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease. Alzheimer’s disease mouse models were established by injection of beta amyloid 1−42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1−42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

INTRODUCTION Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.