Evidence of progenitor cell lineage rerouting in the adult mouse hippocampus

• Published in: bioRxiv
• Main Authors: Daniela Ms Moura, Juliana Alves Brandão, Lentini, Celia, Heinrich, Christophe, Queiroz, Claudio M, Costa, Marcos R
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 09.06.2020
• Subjects: Astrocytes; Cell lineage; Cytology; Dentate gyrus; Doublecortin protein; Glial fibrillary acidic protein; Gliogenesis; Hippocampus; Inflammation; Kainic acid; Neural stem cells; Neurogenesis; Pilocarpine; Progenitor cells; Recombination; Tamoxifen; Transgenic mice; Trinucleotide repeats
• DOI: 10.1101/2020.06.08.140467

Summary Cell lineage in the adult hippocampus comprises multipotent and neuron-committed progenitors. In the present work, we fate-mapped neuronal progenitors using Dcx-CreERT2 and CAG-CAT-EGFP double-transgenic mice (cDCX/EGFP). We show that three days after tamoxifen-mediated recombination in cDCX/EGFP adult mice, GFP+ cells in the dentate gyrus co-expresses DCX and about 6% of these cells are proliferative neuronal progenitors. After 30 days, 20% of GFP+ generated from these progenitors differentiate into GFAP+ astrocytes. Administration of the chemoconvulsants kainic acid (KA) or pilocarpine (PL) led to a significant increase in the number of GFP+ cells in both ipsi and contralateral dentate gyrus. However, while PL favored the differentiation of neurons in both ipsi- and contralateral sides, KA stimulated neurogenesis only in the contralateral side. In the ipsilateral side, KA injection led to an unexpected increase of astrogliogenesis in the Dcx-lineage. These different effects of KA and PL in the Dcx-lineage are associated with distinct alterations of the parvalbuminergic plexus and inflammatory responses in the hippocampi. Finally, we also observed a small number of GFP+/GFAP+ cells displaying radial-glia morphology ipsilaterally 3 days after KA administration, indicating that Dcx-progenitors could regress to a multipotent stage. Altogether, our data suggest that cell lineage in the adult hippocampus is not unidirectional and can be modulated by environmental signals. Competing Interest Statement The authors have declared no competing interest.