No abstract

Resveratrol (RVTL) is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg) induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX)-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging.

SUMMARYNeuropsychiatric diseases (NPD) are characterized by changes in brain plasticity involving alterations in the morphology and functionality of neurons. However, affectations of the neuronal development (neurogenesis) in the adult brain are also shown.The neurogenic process is widely regulated by different factors such as genes, microenvironment, hormones, neurotransmitters, environmental cues and, also, nutrition. Thus, alterations in these factors negatively impact the neuronal development.Several studies performed in humans have revealed alterations of neurogenesis in NPD. However, most of the knowledge derives from studies done in animal models of NPD. The evidences from animal models are controversial, thus the use of human-induced pluripotent stem cells as a model of NPD has marked a way to study alterations in the neuronal development. Recently, the use of another cellular model for studying NPD has been proposed. Multipotent stem cells derived from olfactory epithelium (MOESCs) are a good candidate. However, evidences are scarce and deeper studies are necessary to know if there is or not a correlation of alterations in neuronal development in the OE with the changes observed in the brain; or if the MOESCs can mimic alterations shown in NPD that could let to get more knowledge about the factors promoting these diseases.Thus, in this review we discuss basic information about adult neurogenesis under physiological and non-physiological conditions in the hippocampus, olfactory bulb and olfactory epithelium.Key words: Neurogenesis, neuropsychiatric disorders, aging; stem cells. RESUMENLas enfermedades neuropsiquiátricas (ENP) se caracterizan por cambios en la plasticidad cerebral que incluyen la pérdida neuronal en regiones específicas en el encéfalo, cambios en la transmisión sináptica originada por alteraciones en los contactos sinápticos y también por la expresión de genes. Además, otro proceso que forma parte de la plasticidad cerebral y que también se encuentra afectado en las ENP es la generación de nuevas neuronas (neurogénesis).El proceso neurogénico en el adulto es regulado de manera fina por diversos factores como los aspectos genéticos, celulares, el microambiente, los elementos neuroquímicos, los ambientales y los nutricionales. Las alteraciones de estos factores impactan en el desarrollo y en la función de las nuevas neuronas.Algunos estudios realizados en humanos han revelado las alteraciones en la neurogénesis en algunos ENP. Sin embargo los mayores avances logrados han utilizado modelos animales de ENP. En algunos casos estas evidencias son controvertidas y recientemente se han tratado de aclarar utilizando cultivos de células madre pluripotenciales-inducibles humanas como modelos de ENP. Otro modelo que se ha propuesto para estudiar las alteraciones en el desarrollo neuronal en las ENP son las células madre multipotenciales del epitelio olfatorio (CMPEO). Sin embargo las evidencias obtenidas con las CMPEO son escasas y resulta necesario demostrar si existe o no un correlato con las alter...