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Published on: May 12, 2015
P2X7 expression patterns in the developing Fmr1-knockout mouse hippocampus
Matthew Napier1,2, Ashish Kumar3, Natasha Szulist1
1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Insights
Fragile-X Syndrome (FXS) involves altered P2X7 receptor expression in the developing Fmr1 KO hippocampus. This purinergic signaling change may impact neurite outgrowth and synaptic refinement in FXS mouse models.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Fragile-X Syndrome (FXS) is a leading genetic cause of intellectual disability.
- Hippocampus dysfunction is a key feature of FXS, but underlying mechanisms are not fully understood.
- Purinergic signaling plays a role in brain development, yet its involvement in FXS is unclear.
Purpose of the Study:
- To investigate the role of purinergic signaling, specifically the P2X7 receptor, in the developing hippocampus of the Fmr1 KO mouse model of FXS.
- To characterize P2X7 expression patterns and cell-specific localization in the developing Fmr1 KO hippocampus.
Main Methods:
- Utilized the Fmr1 KO mouse model.
- Quantified P2X7 expression in whole hippocampus tissue at postnatal days 14 and 21.
- Employed immunofluorescence to assess cell-specific P2X7 colocalization with neurons and microglia.
- Analyzed sex-specific differences in P2X7 expression and localization.
Main Results:
- P2X7 receptor expression was reduced in Fmr1 KO hippocampus tissue at P14 and P21.
- P2X7 showed increased colocalization with microglia and reduced colocalization with neurons in Fmr1 KO mice.
- A sex-specific reduction in neuronal P2X7 colocalization was observed in males, while females exhibited reduced absolute neuronal P2X7 expression.
Conclusions:
- P2X7 receptor expression and localization are significantly altered during hippocampal development in the Fmr1 KO mouse model.
- These alterations in purinergic signaling may contribute to the hippocampus dysfunction observed in FXS.
- Findings highlight P2X7 as a potential target for understanding and treating FXS-related neurodevelopmental deficits.
Abstract:
Fragile-X Syndrome (FXS) is the leading monogenetic cause of intellectual disability among children but remains without a cure. Using the Fmr1 KO mouse model of FXS, much work has been done to understand FXS hippocampus dysfunction. Purinergic signaling, where ATP and its metabolites are used as signaling molecules, participates in hippocampus development, but it is unknown if purinergic signaling is affected in the developing Fmr1 KO hippocampus. In our study, we characterized the purinergic receptor P2X7. We first found that P2X7 was reduced in Fmr1 KO whole hippocampus tissue at P14 and P21, corresponding to the periods of neurite outgrowth and synaptic refinement in the hippocampus. We then evaluated the cell-specific expression of P2X7 with immunofluorescence and found differences between WT and Fmr1 KO mice in P2X7 colocalization with hippocampal microglia and neurons. P2X7 colocalized more with microglia at P14 and P21, but there was a sex-specific reduction in P2X7 colocalization with neurons. In contrast, male mice at P14 and P21 showed reduced neuronal P2X7 colocalization compared to females, but only females showed reduced absolute neuronal P2X7 expression across the dorsal hippocampal formation. Together, our results suggest that P2X7 expression is altered during Fmr1-KO hippocampal development, potentially influencing several developmental processes in the Fmr1-KO hippocampus formation.
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