Increased proliferation and neuronal fate in prairie vole brain progenitor cells cultured in vitro: effects by social exposure and sexual dimorphism
Authors: Ávila-González Daniela , Romero-Morales Italo , Caro Lizette , Martínez-Juárez Alejandro , Young Larry J. , Camacho-Barrios Francisco , Martínez-Alarcón Omar , Castro Analía E. , Paredes Raúl G. , Díaz Néstor F. , Portillo Wendy 
Published: November 2023

Abstract
Background
The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro.

Results
Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context.

Conclusion
Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation.
Highlights

Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles.

Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles.

The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context.

Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context.

Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.