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Published on: September 28, 2017
Altered expression of circadian clock gene, mPer1, in mouse brain and kidney under morphine dependence and withdrawal
Xiaojia Wang1, Yueqi Wang, Haoyang Xin
1West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, China. wxjia86@sohu.com
Abstract:
Every physiological function in the human body exhibits some form of circadian rhythmicity. Under pathological conditions, however, circadian rhythmicity may be disrupted. Patients infected with HIV or addicted to drugs of abuse often suffer from sleep disorders and altered circadian rhythms. Early studies in Drosophila suggested that drug seeking behavior might be related to the expression of certain circadian clock genes. Our previous research showed that conditioned place preference with morphine treatment was altered in mice lacking the Period-1 (mPer1) circadian clock gene. Thus, we sought to investigate whether morphine treatment could alter the expression of mPer1, especially in brain regions outside the SCN and in peripheral tissues. Our results using Western blot analysis showed that the mPER1 immunoreactivity exhibited a strong circadian rhythm in the brains of the control (Con), morphine-dependent (MD), and morphine-withdrawal (MW) mice. However, the phase of the circadian rhythm of mPER1 expression in the brains of MD mice significantly differed from that of the Con mice (p < 0.05). In contrast to mPER1 expression in the brain, the circadian rhythm of mPER1 immunoreactivity in the kidneys was abolished after morphine administration, whereas the Con mice maintained robust circadian rhythmicity of mPER1 in the kidney. Therefore, the effect of morphine on the circadian clock gene mPer1 may vary among different organs, resulting in desynchronization of circadian function between the SCN and peripheral organs.
Insights
Morphine disrupts the circadian rhythm of the mPer1 clock gene in mouse brains, altering its expression phase. However, in the kidneys, morphine completely abolishes the mPer1 circadian rhythm, indicating organ-specific effects.
Area of Science:
- Chronobiology
- Neuropharmacology
- Molecular Biology
Background:
- Circadian rhythms govern physiological functions, but can be disrupted by pathological conditions like drug addiction.
- Drug abuse and HIV infection are linked to sleep disorders and altered circadian rhythms.
- Previous research suggests a connection between circadian clock genes and drug-seeking behavior.
Purpose of the Study:
- To investigate the impact of morphine treatment on the expression of the mPer1 circadian clock gene.
- To examine mPer1 expression in brain regions outside the suprachiasmatic nucleus (SCN) and in peripheral tissues.
- To determine if morphine alters the circadian rhythmicity of mPer1.
Main Methods:
- Western blot analysis was used to measure mPER1 immunoreactivity.
- Experiments were conducted on control, morphine-dependent, and morphine-withdrawal mice.
- Circadian rhythms of mPER1 expression were assessed in both brain and kidney tissues.
Main Results:
- mPER1 immunoreactivity showed a strong circadian rhythm in the brains of all groups.
- The phase of the mPER1 circadian rhythm in the brains of morphine-dependent mice significantly differed from controls.
- The circadian rhythm of mPER1 immunoreactivity in the kidneys was abolished in morphine-administered mice, unlike controls.
Conclusions:
- Morphine administration alters the circadian rhythm of mPer1 expression in the mouse brain.
- Morphine abolishes the circadian rhythm of mPer1 in the kidney, while controls maintain it.
- The effects of morphine on the mPer1 clock gene vary across organs, potentially causing desynchronization between the SCN and peripheral tissues.
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