Pregabalin enhances myelin repair and attenuates glial activation in lysolecithin-induced demyelination model of rat optic chiasm

Daneshdoust, Danyal; Khalili-Fomeshi, Mohsen; Ghasemi-Kasman, Maryam; Ghorbanian, Davoud; Hashemian, Mona; Gholami, Mohammad; Moghadamnia, Ali Akbar; Shojaei, Amir

doi:10.1016/j.neuroscience.2016.12.037

Cited by 23 publications

(11 citation statements)

References 28 publications

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“…Recent data demonstrate that microglia disrupts the mesolimbic system (Taylor et al, 2015). Assuming that PGB would modulate the activity on these non-neuronal cells as previously observed (Daneshdoust et al, 2017), it would be tempting to examine this indirect relationship between PGB and VTA DA neurons. In a last series of experiments, we showed that repeated administration of PGB for 4 consecutive days at the dose of 60 mg/kg (chosen to mimic the CPP test conditions), did not influence the DA system.…”

Section: Discussionmentioning

confidence: 90%

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

et al. 2019

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Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain and generalized anxiety disorders. Pregabalin acts on different neurotransmission systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid is still a matter for debate. The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the Nucleus Accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Collectively these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders or addiction and to identify the key neurotransmitter system involved.

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Section: Discussionmentioning

confidence: 90%

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

et al. 2019

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“…Several previous studies demonstrated that pregabalin reduced the incidence of anxiolytic, analgesic, acute, and chronic neuropathic pain and also exerted opioid-sparing effects [15][16][17]. Moreover, several experimental studies reported that pregabalin decreased apoptosis and also exerted neuroprotective and antiinflammatory effects in spinal cord injury models [12,13]; furthermore, it reduced the severity of autoimmune encephalomyelitis [14], improved myelin repair, and reduced glial activation [11].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was found to be effective against postoperative pain [4,9,10]. Additionally, some experimental studies have demonstrated that pregabalin has neuroprotective, antiinflammatory, and apoptosis-reducing effects, and it was effective for improving myelin production, cerebral ischemia, and reperfusion injury [11][12][13][14]. However, no randomized clinical trials in the literature have reported the effect of pregabalin on ischemia-reperfusion.…”

Section: Introductionmentioning

confidence: 99%

The effect of pregabalin on the tourniquet induced ischemia-reperfusion injury. A Prospective Randomized Study

Karaca¹,

Pınar²,

Ozgur³

et al. 2019

Turk J Med Sci

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The aim of this study was to investigate the efficacy of pregabalin on ischemia-reperfusion injuries. Materials and methods: Fifty-four patients were randomly assigned into 2 groups. A 150-mg tablet of pregabalin was given the night before and then 1 h before the operation for patients in Group P (pregabalin group, n = 27). A placebo was given to patients in Group C (control group, n = 27) at the same times. After combined spinal-epidural anesthesia was performed, venous blood samples were taken before tourniquet inflation (t 1), just before tourniquet deflation (t 2), and 20 min after tourniquet deflation (t 3) for the analysis of total antioxidant status (TAS), total oxidant status (TOS), catalase (CAT), and ischemia-modified albumin (IMA). Results: There was no significant difference in TAS levels between the groups for the t 3 period. However, the TAS in Group P was significantly higher in the t 3 period than the t 2 period (mean ± SD, 0.46 ± 0.1 vs. 0.38 ± 0.2 mmol of Trolox equivalent/L, respectively; P < 0.05). The CAT level in the t 3 period was significantly higher in Group P than Group C (mean ± SD, 53.04 ± 32.1 vs. 35.46 ± 17.2 µmol/ formaldehyde, respectively; P < 0.05). In the t 3 period, the TOS was significantly lower in Group P than Group C (mean ± SD, 11.97 ± 5 vs. 18.29 ± 9.9 pg/mL, respectively; P < 0.05). The TOS in Group P was significantly lower in the t 3 period than the t 2 period (mean ± SD, 11.97 ± 5 vs. 18.98 ± 10.7 pg/mL, respectively; P < 0.0001). Conclusion: Pregabalin has no marked antioxidant activity, but it contributes to the antioxidant defense system of an organism.

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“…The neurotransmission signaling is also greatly impacted by abnormal lipid metabolism. Lysophosphatidylcholines (LPCs), byproducts of the phosphatidylcholine → arachidonic-acid hydrolysis, are potent membrane-dissolving molecules, and are known to induce demyelination [30][31][32][33][34][35] , negatively impacting the speed and timing of neuronal signals. Therefore, the dysregulation of arachidonic acid signaling, along with the augmentation of LPC levels in MET pups, may imply decreased myelinations and, thus, disrupted circuit connectivity.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis

et al. 2020

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The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving mediate these effects is, however, unknown. Here, we show that the behavioral deficits of MET are independent of the early life mother-infant interaction. We also show that MET produces in early life profound changes in the brain C1 pathway components as well as glutamate transmission, mitochondrial function, and lipid metabolism. Bioinformatics analysis integrating metabolomics and transcriptomic data reveal dysregulations of glutamate transmission and lipid metabolism, and identify perturbed pathways of methylation and redox reactions. Our transcriptomics Linkage analysis of MET mice and schizophrenia subjects reveals master genes involved in inflammation and myelination. Finally, we identify potential metabolites as early biomarkers for neurodevelopmental defects and suggest therapeutic targets for schizophrenia.

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Pregabalin enhances myelin repair and attenuates glial activation in lysolecithin-induced demyelination model of rat optic chiasm

Cited by 23 publications

References 28 publications

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

The effect of pregabalin on the tourniquet induced ischemia-reperfusion injury. A Prospective Randomized Study

Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis

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