Growth hormone is protective against acute methadone-induced toxicity by modulating the NMDA receptor complex

Nylander, Erik; Grönbladh, Alfhild; Zelleroth, Sofia; Diwakarla, Shanti; Nyberg, Fred; Hallberg, Mathias

doi:10.1016/j.neuroscience.2016.10.019

Cited by 34 publications

(34 citation statements)

References 44 publications

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“…This effect might be related to an antagonistic effect of PRL on glutamate receptors. In accordance, a recent study, showed that rhGH, a member of the growth hormone-like superfamily, which includes PRL, acted as a neuroprotector against methadone-induced toxicity in primary cultures of cortical neurons, through the alteration of the expression of NMDA receptors subunits [38]. Our group is currently exploring the possible effect of PRL on the modulation of glutamate receptors in the present neurotoxicity model.…”

Section: Discussionsupporting

confidence: 68%

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Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

et al. 2017

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Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca2+] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca2+]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 68%

“…The current results also show that PRL prevents the mitochondrial dysfunction resulting from Glu-induced excitotoxity. A similar effect was observed by recombinant human growth hormone (rhGH), which prevents mitochondrial damage induced by methadone, a specific agonist of NMDA receptors [38]. …”

Section: Discussionmentioning

confidence: 72%

Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

et al. 2017

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“…Unlike what happens in children and adults with GHD, few studies show that the administration of GH increases cognition in non-GHD human patients with cognitive deficits produced as a result of different pathologies [23,24,25,26,27,28]. However, these positive effects of GH have been widely demonstrated in different experimental animal models [29,30,31,32,33]; even in old animals, in which the cognitive impairment of hippocampal-dependent functions, such as learning and memory, is associated with a decrease in the secretion of GH and IGF-I, as in our species [4,17,18,32].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, GH may have produced an increase in blood flow to the brain, which would allow increased uptake of FDG. Recently, we described that GH induces a significant reparative effect on the endothelial dysfunction that appears after atherogenic stimuli, such as hypercholesterolemia [70]; moreover, GH is a mitochondrial protector [26,71], and atherogenesis is related to oxidative stress [70]. Given that the patient we treated had high levels of cholesterol and triglycerides in plasma, it is also possible that, despite the short time of treatment, GH may have contributed to improving blood supply to the brain, facilitating the uptake and metabolism of glucose and producing the changes described here (both in terms of PET-SCAN images and cognitive tests).…”

Section: Discussionmentioning

confidence: 99%

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Devesa¹,

Núñez²,

Agra³

et al. 2018

IJMS

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(1) Background: We analyzed, using PET-SCAN and cognitive tests, how growth hormone (GH) could act in the brain of an older woman, not deficient in GH, who showed mild cognitive alterations (MCI) and had a genotype of ApoE 4/3 and familial dyslipidemia. (2) Methods: After performing a first psychometric study (TAVEC verbal learning test), the metabolic activity of brain structures related to knowledge, memory, and behavior was analyzed using 18-F fluorodeoxyglucose PET-SCAN. The patient was then treated with GH (0.4 mg/day, subcutaneous) for three weeks and on the last day under this treatment, a new PET-SCAN was performed. One month after beginning treatment with GH, a new TAVEC test was performed. (3) Results: GH administration normalized the cognitive deficits observed in the first psychometric test and significantly (p < 0.025) increased the metabolic activity in practically all brain cortical areas, specifically in the left hippocampus and left amygdala, although not in the left parahippocampus. (4) Conclusions: This study demonstrates for the first time the positive effects of GH on cerebral metabolism in a patient without GH deficiency, recovering the function of affected areas related to knowledge, memory, and behavior in an elderly patient with MCI.

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“…For methadone, two signal paths have been suggested: one for binding to opioid receptors and another for acting as an antagonist in NMDR . It seems that the pathway of NMDR would have more evident effects on the toxicity of methadone in cortical cell cultures …”

Section: Resultsmentioning

confidence: 99%

Suppressor capacity of iron nanoparticles biosynthesized using Salvia chloroleuca leaf aqueous extract on methadone‐induced cell death in PC12: Formulation a new drug from relationship between the nanobiotechnology and neurology sciences

Ahmeda

Zangeneh

Mansooridara

et al. 2020

Applied Organom Chemis

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Metallic nanoparticles have gained significant attention in the area of biomedical technology. Because of its high surface area, metallic nanoparticles are being widely used in various fields including the medical and engineering sciences. One of the valuable applications of metallic nanoparticles especially copper, zinc, and iron nanoparticles is increasing the physiological function of central nervous system. Besides, Iranian people are using the Salvia chloroleuca for neuroprotective properties. In the present research, iron nanoparticles were biosynthesized by S. chloroleuca leaf aqueous extract as reducing and stabilizing agents. Also, we revealed the protective effect of FeNPs in methadone‐treated PC12 cells. FeNPs were characterized and analyzed using common nanotechnology techniques including FT‐IR, UV–Vis. spectroscopy; EDS, TEM, and FE‐SEM. TEM and FE‐SEM images revealed a uniform spherical morphology for FeNPs. In the biological part of the current study, the both treatments of FeNPs significantly (p ≤ 0.01) reduced the cell cytotoxicity and cell death index as well as increased the cell viability and cell proliferation in methadone‐treated PC12 cells. In these treatments, mitochondrial membrane potential significantly (p ≤ 0.01) increased compared to methadone‐induced PC12 cells. DPPH free radical scavenging test was did to evaluate the antioxidant potentials of FeCl3, S. chloroleuca, and FeNPs. DPPH test indicated similar antioxidant activities for S. chloroleuca, FeNPs, and butylated hydroxytoluene. In current experiment, we concluded that iron nanoparticles biosynthesized by S. chloroleuca leaf aqueous extract suppressed methadone‐induced cell death in a dose‐dependent manner in PC12 cells.

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Growth hormone is protective against acute methadone-induced toxicity by modulating the NMDA receptor complex

Cited by 34 publications

References 44 publications

Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Suppressor capacity of iron nanoparticles biosynthesized using Salvia chloroleuca leaf aqueous extract on methadone‐induced cell death in PC12: Formulation a new drug from relationship between the nanobiotechnology and neurology sciences

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