Adult neurogenesis

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Group leader:  Luca Bonfanti and  Paolo Peretto

adult-neurogenesis_bonfanti

Main goal 
Main interest of this group is the study of persistent neurogenesis in the brain of adult mammals. Research performed by the group components has contributed to the definition of morphological, molecular, and functional features of adult neurogenic zones and neural stem cell niches.

Experimental models
The elective model of study is the subventricular zone-olfactory bulb system (SVZ-OB), which contains the primary source of neural stem cells and progenitors of the adult central nervous system (CNS) in mammals.

Two decades after the discovery of adult neurogenesis, although the SVZ-OB system remains an excellent model to investigate the issue of brain plasticity, it represents a small exception in the context of a substantially non-renewable CNS tissue, unable to self-repair after damage (vascular and traumatic lesions, neurodegenerative diseases). Hence, during the last few years, we directed our studies toward the search of alternative sources of endogenous progenitors (independent from the adult neurogenic zones) to be considered for potential therapeutical perspectives.

These studies have contributed to the identification of new, spontaneous neurogenic events in other adult mammals, such as rabbit and guinea pig, within regions which are generally considered incapable to generate neurons during adulthood (e.g. the striatum and cerebellum). This may be an example of “constitutive neurogenesis” independent from persistent germinal layers and attributable to local progenitors widely dispersed in the mature brain parenchyma.

Projects
The future lines of research are pointed in three directions:

  • to further investigate the adult neurogenic zones and the stem cell niches which sustain their activity, by focussing on different aspects (identification of the stem cell elements and their progeny, determination of the functional role under both physiological condition and brain lesions, comparative analyses in different mammalian species);
  • to explore the physiological meaning of brain local parenchymal progenitors (origin, species- and age-specific distribution, subpopulations, mechanisms of activation, and functional role).
    This knowledge is essential in order to understand mechanisms leading to spontaneous activation of neural progenitors and their interaction with the brain tissue;
  • to study activation of local progenitors (both those that are quiescent and those which sustain spontaneous neurogenesis) in different experimental and pathological conditions (chemically-induced lesions, animal models of acute and progressive neurodegeneration). 

From the comparison of results obtained in diverse physiological and experimental conditions, we expect to unravel common themes and local variations in the mechanisms regulating adult mammalian neurogenesis. 
The final aim could be to identify the appropriate cellular, molecular, and environmental conditions leading to possible alternative therapeutic strategies based on the exploitation of the endogenous neurogenic potential coming from both germinal layer-derived stem/progenitor cells (i.e. SVZ-OB system) and local progenitors dispersed in the mature brain parenchyma.

Methodological approaches

In vivo approaches:

  • Morphological and immunocytochemical analysis of the nervous system in confocal microscopy, with special reference to cell proliferation (using endogenous and exogenous markers), cell specification/differentiation (using cell tracers and viruses), cell death.
  • Ultrastructural analysis:  conventional electron microscopy, immunoelectronmicroscopy using pre-and post-embedding techniques.
  • Quantitative analyses and 3D reconstructions of cells and brain regions.

In vitro approaches:

  • Primary cultures of the nervous system
  • Tissue explants (neurogenic zones and brain parenchyma)
  • Co-coltures
  • Organotypic cultures

News

Non-neurogenic SVZ-like niche in aquatic mammals devoid of olfaction

Brain Structure & Function , February 2017
Parolisi R, Cozzi B, Bonfanti L

31 march 2017

Opposite-sex attraction in male mice requires testosterone dependent regulation of adult olfactory bulb neurogenesis

Scientific Reports , October 2016
Schellino R, Trova S, Cimino I, Farinetti A, Jongbloets BC, Pasterkamp RJ, Panzica G, Giacobini P, De Marchis S, Peretto P.

25 january 2017