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Published on: May 28, 2015
Phenotypic changes in calbindin D28K immunoreactivity in the hippocampus of Fmr1 knockout mice
M Angeles Real1, M Pilar Simón, Raúl Heredia
1University of Málaga, Department of Cell Biology, Genetics, and Physiology, Málaga, Spain.
Abstract:
Fragile X syndrome (FXS), the most prevalent form of inherited mental retardation, is caused by the lack of FMRP (fragile mental retardation protein) as a result of the transcriptional silencing of the FMR1 gene. Here we analyze the immunohistochemical expression of the calbindin D28K protein in the hippocampus of Fmr1 knockout (KO) mice and compare it with that of their wildtype (WT) littermates. The spatial distribution pattern of calbindin-immunoreactive cells in the hippocampus was similar in WT and KO mice but for each age studied (ranging from 3.5-8 months) the dentate gyrus of Fmr1-KO mice showed a significant reduction in calbindin-immunoreactive granule cells. Also, the number of calbindin-immunoreactive cells was reduced in the CA1 pyramidal layer in KO mice compared to their WT littermates. In addition, Frm1-KO mice showed a group of calbindin-immunoreactive cells located only in the left CA3b subregion that was only sometimes observed in WT mice. Overall, the absence of FMRP results in a dysregulation of the calbindin protein expression in the hippocampus. This dysregulation is cell type- and time-dependent and as a consequence key elements of the hippocampal trisynaptic circuitry may lack calbindin in critical periods for normal memory/learning abilities to be achieved and may explain some of the FXS symptoms observed in the Fmr1-KO mouse model.
Insights
Fragile X syndrome (FXS) in mice is linked to altered calbindin D28K protein expression in the hippocampus. This dysregulation in FMR1 gene knockout mice may impact learning and memory, explaining some FXS symptoms.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Fragile X syndrome (FXS) is the most common inherited intellectual disability.
- It results from the absence of fragile mental retardation protein (FMRP) due to FMR1 gene silencing.
- Hippocampal circuitry is crucial for learning and memory.
Purpose of the Study:
- To investigate the expression of calbindin D28K protein in the hippocampus of Fmr1 knockout (KO) mice.
- To compare calbindin D28K expression patterns between Fmr1-KO mice and wildtype (WT) littermates.
Main Methods:
- Immunohistochemical analysis of calbindin D28K protein expression.
- Comparison of cell distribution and number in the hippocampus of Fmr1-KO and WT mice across different ages (3.5-8 months).
Main Results:
- Fmr1-KO mice showed a significant reduction in calbindin-immunoreactive granule cells in the dentate gyrus.
- The CA1 pyramidal layer had fewer calbindin-immunoreactive cells in Fmr1-KO mice compared to WT.
- An unusual cluster of calbindin-immunoreactive cells was observed in the CA3b subregion of Fmr1-KO mice.
Conclusions:
- The absence of FMRP leads to dysregulated calbindin D28K protein expression in the hippocampus.
- This dysregulation is cell type- and time-dependent.
- Impaired calbindin expression in hippocampal circuits may contribute to learning and memory deficits observed in FXS models.
