期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 12, 期 4, 页码 1281-1293出版社
WILEY
DOI: 10.1046/j.1460-9568.2000.01015.x
关键词
delta opioid receptors; mu opioid receptors; apoptosis; cell division; cerebellar development; endogenous opioid system; neuronal differentiation; opiate drug abuse
资金
- NIDA NIH HHS [R01 DA006204, DA06204] Funding Source: Medline
Although opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin-derived peptides, as well as specific mu and delta, but negligible kappa, opioid receptors. The developmental effects of opioids were highly selective. Morphine-induced mu receptor activation inhibited DNA synthesis, while a preferential delta(2)-receptor agonist ([D-Ala(2)]-deltorphin II) or Met-enkephalin, but not the delta(1) agonist [D-Pen(2), D-Pen(5)]-enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous mu and delta opioid ligand-receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors.
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