Additive effect of mPer1 and mPer2 antisense oligonucleotides on light-induced phase shift
H Wakamatsu1, S Takahashi, T Moriya
1Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
Abstract:
It is well known that light induces both mPer1 and mPer2 mRNA in the suprachiasmatic nucleus. We have reported that mPer1 antisense oligonucleotides (ODNs) inhibited the light-induced phase delays of mouse locomotor rhythm. In this study, we asked whether both or either mPer1 or mPer2 expression is necessary to induce the phase shift. We examined the effects of inhibition of mRNA expression on light-induced phase delays of mouse circadian behavior rhythm. Light-induced phase delays were moderately attenuated by microinjection of mPer1 or mPer2 antisense ODN, but not by mPer3 antisense or mPer1, mPer2 scrambled ODNs, whereas following simultaneous injection of both mPer1 and mPer2 antisense ODNs they disappeared. The present results suggest that acute induction of mPer1 and mPer2 gene play an additive effect on photic entrainment.
Insights
Both mPer1 and mPer2 gene expression are necessary for light-induced phase delays in mouse circadian rhythms. Inhibiting either gene moderately attenuated delays, while inhibiting both eliminated them, suggesting an additive effect on photic entrainment.
Area of Science:
- Chronobiology
- Molecular Biology
- Neuroscience
Background:
- Light exposure is known to induce mPer1 and mPer2 mRNA in the suprachiasmatic nucleus.
- Previous research indicated that mPer1 antisense oligonucleotides (ODNs) inhibit light-induced phase delays in mouse locomotor rhythm.
Purpose of the Study:
- To determine if mPer1 and/or mPer2 gene expression is essential for light-induced circadian rhythm phase shifts.
- To investigate the specific roles of mPer1 and mPer2 in the photic entrainment process.
Main Methods:
- Utilizing antisense ODNs to inhibit the expression of mPer1, mPer2, and mPer3 mRNA in mice.
- Examining the impact of antisense ODN microinjections on light-induced phase delays in circadian behavior rhythms.
- Employing scrambled ODNs as controls to ensure specificity of the antisense effects.
Main Results:
- Microinjection of mPer1 or mPer2 antisense ODNs moderately attenuated light-induced phase delays.
- No significant effect on phase delays was observed with mPer3 antisense ODNs or scrambled ODNs.
- Simultaneous injection of both mPer1 and mPer2 antisense ODNs resulted in the complete disappearance of light-induced phase delays.
Conclusions:
- Both mPer1 and mPer2 gene induction are crucial for normal light-induced phase delays in mouse circadian rhythms.
- The expression of mPer1 and mPer2 genes appears to have an additive effect on the process of photic entrainment.
- These findings highlight the cooperative role of mPer1 and mPer2 in mediating the circadian system's response to light cues.
