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[Effects of beta-endorphin on glutamate neurotoxicity]
1Department of Pharmacology, School of Medicine, Nanjing University, Nanjing 210093.
Abstract:
The effects of beta-endorphin(beta-End) on monosodium glutamate(MSG) neurotoxicity were studied via morphological observation and image analysis of neuronal areas, together with the determination of intracellular free calcium concentration ([Ca2+]i) in single neuron and radioimmunoassay for beta-End contents. beta-End(1.0 mg.kg-1, s.c.) was found to obviously aggravate the neuronal injury in the arcuate nucleus of hypothalamus induced by MSG(0.5 g.kg-1, s.c.). Just as MSG increased [Ca2+]i significantly, beta-End(2.0 g.L-1) itself also increased it, though the extent of elevation was smaller than that of MSG(17.0 mg.L-1). The obvious changes of [Ca2+]i induced by both MSG and beta-End were partially reversed after pretreatment with verapamil. On the other hand, the content of beta-End in different areas of the brain were augmented following the addition of MSG and further elevated by morphine treatment. These findings suggest that the mechanisms of the enhancing effect of beta-End on glutamate neurotoxicity were linked to the aggravation on the disruption of intracellular Ca2+ homeostasis induced by MSG. Moreover, the fact that opioids promote beta-End release induced by MSG may be involved in the mechanisms as well.
Insights
Beta-endorphin exacerbates monosodium glutamate neurotoxicity by disrupting calcium homeostasis in neurons. This effect is linked to opioid-induced beta-endorphin release, suggesting a complex interaction in brain injury.
Area of Science:
- Neuroscience
- Neuroendocrinology
- Cellular Biology
Context:
- Monosodium glutamate (MSG) is a known neurotoxin, particularly affecting hypothalamic neurons.
- Beta-endorphin (beta-End), an endogenous opioid peptide, plays roles in pain and stress responses.
- Intracellular calcium ([Ca2+]i) is critical for neuronal function and survival.
Purpose:
- To investigate the effects of beta-endorphin on monosodium glutamate (MSG)-induced neurotoxicity.
- To determine the role of intracellular calcium ([Ca2+]i) in this interaction.
- To explore the influence of opioids on beta-endorphin levels in the context of MSG neurotoxicity.
Summary:
- Beta-endorphin (1.0 mg/kg) significantly aggravated MSG (0.5 g/kg)-induced neuronal injury in the hypothalamus.
- Both MSG and beta-endorphin increased intracellular free calcium concentration ([Ca2+]i), with MSG having a greater effect.
- Verapamil partially reversed the calcium changes induced by MSG and beta-endorphin.
- MSG administration increased brain beta-endorphin content, further elevated by morphine.
- Opioid-induced beta-endorphin release may contribute to the enhancement of MSG neurotoxicity.
Impact:
- Reveals a novel mechanism by which beta-endorphin can worsen excitotoxicity.
- Highlights the critical role of calcium dysregulation in neurotoxic processes.
- Suggests potential therapeutic targets for conditions involving excitotoxicity and opioid modulation.