Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells.
Neurogenesis is a plastic event modulated by external cues. Systemic inflammation decreases neurogenesis in the dentate gyrus (DG) in part through the proliferative restrain of neural precursor cells (NPCs). To evaluate if inflammation affects the cell cycle progression of particular populations of NPCs, we treated young-adult mice with a single i.p. injection of saline or 1 mg/kg LPS. After 7 days, we analysed proliferation of new BrdU+/DCX+ cells through immunohistochemistry. We extracted the hippocampus and performed a neurosphere assay and a flow cytometric analysis to evaluate proliferation and to identify the phase of the cell cycle in specific populations of DG-derived NPCs. We show that the number of BrdU+/DCX+ cells diminishes in the LPS-treated group and that the number of primary neurospheres derived from LPS-injected animals is significantly reduced compared to the saline-injected group. Flow cytometry revealed that inflammation does not affect the total number of Type 1 BLBP+/TBR2- cells, while the total number of Type 2 intermediate precursor cells (IPCs) (TBR2+) from the LPS-treated group was increased. Cell cycle analysis shows a decrease in the total rate of NPCs in phases S, G2 and M in the LPS-treated group. The percentage of Type 1 BLBP+/TBR2- cells in each cell cycle phase was not different between groups, while there was a fewer number of Type 2 TBR2+ cells in S/G2/M phase. These results show that inflammation alters the appropriate cell cycle progression of Type 2 IPCs, which may contribute to the decrease in the birth rate of DG neurons.
['Melo-Salas|Marlene Sinai|MS|', 'Pérez-Domínguez|Martha|M|', 'Zepeda|Angélica|A|http://orcid.org/0000-0003-0857-1652']
D000818:Animals D001522:Behavior, Animal D002452:Cell Count D002453:Cell Cycle D049109:Cell Proliferation D048429:Cell Size D000089622:Doublecortin Domain Proteins D000089662:Doublecortin Protein D006624:Hippocampus D007249:Inflammation D015850:Interleukin-6 D008070:Lipopolysaccharides D008297:Male D008810:Mice, Inbred C57BL D017628:Microglia D008869:Microtubule-Associated Proteins D009043:Motor Activity D058953:Neural Stem Cells D009479:Neuropeptides D018874:Spheroids, Cellular D015431:Weight Loss
Proliferation Neurogenesis Cell cycle Flow cytometric analysis Disease FACS Neuroinflammation