A mechanism that regulates neurogenesis in the adult brain

Image: Adult mouse hippocampal staining, with the correct morphology of the neuronal laminae in the hippocampus shown in panel C, and the deformation due to the absence of Sema3E-PlexinD1 in panel D.

The study, with recently awarded doctorate students Ágata Mata and Vanessa Gil as first authors, identified the protein Sema3E and its receptor PlexinD1 (known together as Sema3E-PlexinD1) as regulators of the proliferation of adult stem cells of the hippocampus. This is new role for Sema3E-PlexinD1, which until now has been known for its role in the formation of specific connections and synapses during brain development.

The hippocampus is found inside the temporal lobe of the brain, and is one of the first brain regions to suffer damage in Alzheimer’s disease, causing memory problems and disorientation as part of the first symptoms. For a long time, it was believed that adult neurons of the central nervous system couldn’t regenerate, and that the organism is not able to fight memory loss.

Recently, though, the discovery of neurogenesis in some brain areas has broken down this dogma. It’s been found that the cells of the olfactory bulb – a neural structure of the forebrain involved the sense of smell – can regenerate, as do the cells in the subgranular zone of the hippocampus. In this region, a niche of stem cells is responsible for generating new neurons and glial cells that are then functionally integrated. In Alzheimer’s patients, this functional regeneration is altered and isn’t enough to recover the neurodegenerative damage caused by the disease, which contributes to the cognitive deterioration of the patients.

The IBEC researchers carried out tests in mice that revealed that, when Sema3E-PlexinD1 are absent in the hippocampal neurons, an overproduction of new neurons occurs in the niches of the hippocampus that migrate abnormally, causing malformations in this area of ​​the brain. In addition, the Sema3E-PlexinD1 also proved to be crucial for the correct positioning of the new neurons, as well as for the correct development of their connections and the maintenance of brain gamma waves that are generated in the adult hippocampus.

“We know that gamma waves play a role in the maintenance of the central nervous system,” says Ágata Mata, co-first author of the study and PhD researcher at IBEC and the UB. “Our study shows that the absence of Sema3E-PlexinD1in the hippocampus could promote pathological changes not only at the morphological level, but also at the behavioral level.”

Source article: Agata Mata, Vanessa Gil, Jesús Pérez-Clausell, Miguel Dasilva, Mari Carmen González-Calixto, Eduardo Soriano, José Manuel García-Verdugo, Maria V. Sanchez-Vives & José Antonio del Río (2018). New functions of Semaphorin 3E and its receptor PlexinD1 during developing and adult hippocampal formation. Scientific Reports 8, 1381

This research was financed by MEICO, CIBERNED, La Marató de TV3, Generalitat de Catalunya and PRIONET Spain.