Abstract

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.

Highlights

  • Growth hormone (GH) is secreted from the anterior pituitary gland and regulates many physiological functions such as growth, bone metabolism, mood, hunger, and sleep [1]

  • The neuroprotective aspect of the hormone has been demonstrated in several studies [15,16,17], and we have previously reported that GH stabilizes membrane integrity and improves mitochondrial function in primary hippocampal and cortical cell cultures exposed to opioids [18,19]

  • There was an overall effect of recombinant human GH (rhGH) treatment in untreated cells (ANOVA, p < 0.0001), and further post hoc analysis revealed that 1000 nM rhGH significantly decreased lactate dehydrogenase (LDH) release by 3% compared with untreated control cells

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Summary

Introduction

Growth hormone (GH) is secreted from the anterior pituitary gland and regulates many physiological functions such as growth, bone metabolism, mood, hunger, and sleep [1]. The neuroprotective aspect of the hormone has been demonstrated in several studies [15,16,17], and we have previously reported that GH stabilizes membrane integrity and improves mitochondrial function in primary hippocampal and cortical cell cultures exposed to opioids [18,19]. Both the procognitive and neuroprotective properties are further recognized by the fact that GH is able to cross the blood–brain barrier [20] and that GH receptors are expressed in various brain areas associated with cognition, such as the hippocampus and cortex [21]

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