Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Neurogenesis, the creation of new neurons, is a dynamic process influenced by external factors.
• Systemic inflammation is known to suppress neurogenesis in the dentate gyrus (DG), partly by limiting neural precursor cell (NPC) proliferation.

Purpose of the Study:

• To investigate how inflammation impacts the cell cycle progression of specific NPC populations within the DG.
• To determine the effects of lipopolysaccharide (LPS)-induced inflammation on NPC proliferation and differentiation.

Main Methods:

• Young adult mice were injected with saline or LPS.
• Immunohistochemistry was used to analyze BrdU+/DCX+ cell proliferation.
• Neurosphere assays and flow cytometry were performed on hippocampal cells to assess proliferation and cell cycle phases.
• Specific NPC populations (Type 1 and Type 2 intermediate precursor cells) were identified and analyzed.

Main Results:

• LPS treatment significantly reduced the number of new BrdU+/DCX+ cells and primary neurospheres.
• While Type 1 NPCs remained unaffected, Type 2 intermediate precursor cells (IPCs) increased in number.
• Inflammation led to a decrease in NPCs in the S, G2, and M phases of the cell cycle.
• Specifically, Type 2 IPCs showed a reduced presence in the S/G2/M phases.

Conclusions:

• Systemic inflammation disrupts the normal cell cycle progression of Type 2 intermediate precursor cells (IPCs).
• This aberrant cell cycle regulation in Type 2 IPCs likely contributes to the observed decrease in dentate gyrus neurogenesis.