Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells
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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.
KeywordsNeuroinflammation Neurogenesis Flow cytometric analysis FACS Proliferation Disease Cell cycle
We thank Patricia Ferrera, Carlos Castellanos, Erick Espindola and Andrea Bedoya for technical assistance.
MSMS designed and performed experiments; MPD performed experiments; AZ designed experiments and wrote the manuscript.
This work was supported by grants from Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) 203015; 208518.
Compliance with Ethical Standards
Conflict of interest
The authors have no conflicts of interest to declare.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
All authors of the study accept the contents of the manuscript and consent to the submission of the work.
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