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MicroRNA-132 is involved in morphine dependence via modifying the structural plasticity of the dentate gyrus neurons
Meng Jia1,2,3, Xuewei Wang1, Haolin Zhang1
1Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of Ministry of Education and National Health Commission of China, Neuroscience Research Institute, Peking University, Beijing, China.
Abstract:
Repeated morphine exposure has been shown to induce neuronal plasticity in reward-related areas of the brain. miR-132, a CREB-induced and activation-dependent microRNA, has been suggested to be involved in the neuronal plasticity by increasing neuronal dendritic branches and spinogenesis. However, it is still unclear whether miR-132 is related to morphine dependence. Here, we investigate whether miR-132 is involved in morphine dependence and whether it is related to the structural plasticity of the dentate gyrus (DG) neurons. Sprague-Dawley rats are treated with increasing doses of morphine injection for six consecutive days to develop morphine dependence. Our results show that dendritic branching and spinogenesis of the DG neurons of morphine dependent rats are increased. Morphine treatment (24 h) promotes the differentiation of N2a cells stably expressing μ-opioid receptor by up-regulating miR-132 expression. Moreover, inhibiting miR-132 3p (but not 5p) of the DG neurons can reverse the structural plasticity and disrupt the formation of morphine dependence in rats. These findings indicate that miR-132 in the DG neurons is involved in morphine dependence via modifying the neuronal plasticity.
Insights
MicroRNA-132 (miR-132) plays a key role in morphine dependence by altering neuronal plasticity in the dentate gyrus. Inhibiting miR-132 3p reverses structural changes and disrupts dependence formation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Repeated morphine exposure induces neuronal plasticity in brain reward pathways.
- MicroRNA-132 (miR-132) is implicated in neuronal plasticity, affecting dendritic branching and spinogenesis.
- The specific role of miR-132 in morphine dependence remains unclear.
Purpose of the Study:
- To investigate the involvement of miR-132 in morphine dependence.
- To determine if miR-132 is related to the structural plasticity of dentate gyrus (DG) neurons.
Main Methods:
- Morphine dependence was induced in Sprague-Dawley rats over six days.
- Neuronal structural plasticity in DG neurons was assessed.
- miR-132 expression was analyzed in N2a cells and rat DG neurons.
- Inhibition of miR-132 3p and 5p was performed in DG neurons.
Main Results:
- Morphine dependence increased dendritic branching and spinogenesis in DG neurons.
- Morphine treatment upregulated miR-132 expression in differentiating N2a cells.
- Inhibition of miR-132 3p, but not 5p, reversed structural plasticity and disrupted morphine dependence.
Conclusions:
- miR-132 in DG neurons is implicated in morphine dependence.
- miR-132 mediates morphine dependence by modulating neuronal structural plasticity.
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