The restructuring of muscarinic receptor subtype gene transcripts in c-fos knock-out mice
Jan Benes1, Boris Mravec, Richard Kvetnansky
1Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. johnbenes@volny.cz
Abstract:
Although c-Fos plays a key role in intracellular signalling, the disruption of the c-fos gene has only minor consequences on the central nervous system (CNS) function. As muscarinic receptors (MR) play important roles in many CNS functions (attention, arousal, and cognition), the c-fos knock-out might be compensated through MR changes. The aim of this study was to evaluate changes in the M1-M5 MR mRNA in selected CNS areas: frontal, parietal, temporal and occipital cortex, striatum, hippocampus, hypothalamus and cerebellum (FC, PC, TC, OC, stria, hip, hypo, and crbl, respectively). Knocking out the c-fos gene changed the expression of MR in FC (reduced M1R, M4R and M5R expression), TC (increased M4R expression), OC (decreased M2R and M3R expression) and hippocampus (reduced M3R expression). Moreover, gender differences were observed in WT mice: increased expression of all M1-M5R in the FC in males and M1-M4R in the striatum in females. A detailed analysis of MR transcripts showed pre-existing correlations in the amount of MR-mRNA between specific regions. WT mice showed three major types of cortico-cortical correlations: fronto-occipital, temporo-parietal and parieto-occipital. The cortico-subcortical correlations involved associations between the FC, PC, TC and striatum. In KO mice, a substantial rearrangement of the correlation pattern was observed: only a temporo-parietal correlation and correlations between the FC and striatum remained, and a new correlation between the hypothalamus and cerebellum appeared. Thus, in addition to the previously described dopamine receptor restructuring, the restructuring of MR mRNA correlations reveals an additional mechanism for adaptation to the c-fos gene knockout.
Insights
Disrupting the c-fos gene alters muscarinic receptor (MR) mRNA expression and correlations in the mouse brain. These changes in MR mRNA highlight adaptive mechanisms in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The c-Fos protein is crucial for intracellular signaling, but its gene disruption has minimal impact on central nervous system (CNS) function.
- Muscarinic receptors (MR) are vital for CNS functions like attention, arousal, and cognition.
- Compensatory changes in MR may occur following c-fos gene knockout (KO).
Purpose of the Study:
- To investigate alterations in M1-M5 MR mRNA expression in specific CNS regions of c-fos KO mice.
- To analyze changes in MR mRNA correlations between brain regions in c-fos KO mice.
- To identify potential gender-specific differences in MR expression in wild-type (WT) mice.
Main Methods:
- Quantitative analysis of M1-M5 MR mRNA expression in the frontal cortex, parietal cortex, temporal cortex, occipital cortex, striatum, hippocampus, hypothalamus, and cerebellum.
- Comparative analysis between c-fos knockout (KO) mice and wild-type (WT) mice.
- Statistical analysis of MR mRNA expression levels and inter-regional correlations.
Main Results:
- c-fos gene disruption altered MR expression in the frontal cortex (reduced M1R, M4R, M5R), temporal cortex (increased M4R), occipital cortex (decreased M2R, M3R), and hippocampus (reduced M3R).
- Significant gender differences in MR expression were observed in WT mice, particularly in the frontal cortex and striatum.
- KO mice exhibited a rearranged pattern of MR mRNA correlations, with some previously observed correlations disappearing and a new hypothalamus-cerebellum correlation emerging.
Conclusions:
- The c-fos gene knockout induces significant changes in MR mRNA expression across various brain regions.
- The restructuring of MR mRNA correlations suggests an adaptive mechanism in the CNS following c-fos gene disruption.
- These findings contribute to understanding the complex interplay between gene function, receptor expression, and neural adaptation.
More Related Videos
09:29Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
11:10Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
