Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model.

Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination.

Study of adult neurogenesis in the Gallotia galloti lizard during different seasons.

In a previous study we found a seasonal distribution of cell proliferation (the first stage of adult neurogenesis) in the telencephalic ventricular walls of the adult Gallotia galloti lizard. The aim of the present work was to determine the influence of seasonality on the subsequent migration of the resulting immature neurons. We used wild animals injected with bromodeoxyuridine and kept in captivity within 30 days. To confirm the neuronal identity of these cells, we used double immunohistochemical 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX, an early neuronal marker) labeling, as well as autoradiography after the administration of methyl-[³H]thymidine ([³H]T). We found that: (1) the rate of cell division and/or migration from the ventricular walls varied with the season, especially in regions related with olfaction. (2) Immature neuron-like cells appeared to migrate in an apparently radial and tangential way towards different parts of the telencephalic parenchyma. (3) We did not observe ultrastructurally mature neurons until at least 90 days later, a period considerably greater than that reported for other species of vertebrates in similar studies.

Seasonal differences in ventricular proliferation of adult Gallotia galloti lizards.

Lizards present neuronal production throughout the telencephalon in their adult state, both naturally and after experimentally induced brain lesions. As in birds, lizards present seasonal behavioural variations. In birds, such variations have been shown to alter neuronal production. In birds and mammals, lack of stimuli or exposure to stress interferes with adult neurogenetic capacity. The effect of this type of study has not been performed with lizards. In the present study we used bromodeoxyuridine to label dividing cells in the ventricular walls of Gallotia galloti lizards during all four seasons and we investigated the effect of captivity on such proliferation. We found that G. galloti presented a particular distribution that differed from that previously described in other reptiles with respect to regions of greater or lesser proliferative rate. In addition, proliferative rate varied seasonally, with greater production of cells in Spring and low production in Autumn and Winter. Proliferative rate was significantly lower throughout the telencephalon and during all seasons in those lizards kept in captivity as compared with wild animals, even though photoperiod and temperature were similar to natural conditions. Our results indicate that cell production in lizards is species-dependent, varies with seasons and is significantly reduced in captive animals.