Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice

Zhao, Rongjun; Xu, Xiaochen; Xu, Fei; Zhang, Weili; Zhang, Wenlin; Liangmin, Liu; Wang, Weiping

doi:10.1016/j.bbrc.2014.04.130

Cited by 104 publications

(55 citation statements)

References 26 publications

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“…Common mechanisms at the level of ion channels might include the anti-kindling and the calciumantagonist and potassium outward current modulating properties of antiepileptic drugs (Mazza et al, 2007;Ghasemi et al, 2010) and AMPK activators such as valproate and metformin Zhao et al, 2014). This report by Zhao et al (2014) supports the preliminary observation in our laboratory that chronic administrations of metformin (200 mg/kg daily) and artesunate are protective against pentylenetetrazoleinduced seizures. Seizure threshold in diabetic mice is lower than in control mice (Ghasemi et al, 2010).…”

Section: Type 2 Diabetes Mellitus Drug Addiction Bipolar Disorder Asupporting

confidence: 80%

“…This may support the notion that there may be neurological underpinnings of metabolic syndrome, drug addiction, bipolar disorder and epilepsy (Amann and Grunze, 2005;Kenny, 2011). Common mechanisms at the level of ion channels might include the anti-kindling and the calciumantagonist and potassium outward current modulating properties of antiepileptic drugs (Mazza et al, 2007;Ghasemi et al, 2010) and AMPK activators such as valproate and metformin Zhao et al, 2014). This report by Zhao et al (2014) supports the preliminary observation in our laboratory that chronic administrations of metformin (200 mg/kg daily) and artesunate are protective against pentylenetetrazoleinduced seizures.…”

Section: Type 2 Diabetes Mellitus Drug Addiction Bipolar Disorder Asupporting

confidence: 49%

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Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Oriaifo¹

2015

J. Med. Med. Sci

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The prevalence of diabetes and co-morbid diseases, especially in developing countries, may have already exceeded estimates. Accumulating reports indicate considerable underpinnings in the mechanisms of the aetiopathogenesis of metabolic syndrome, bipolar disorder, epilepsy and, recently, substance addiction. Continuing evidence incriminates dysfunction in genetic, mitochondrial and inflammatory cascade mechanisms as contributory factors to the dysregulation of neurotrophic, serotonergic, dopaminergic, adrenergic, glutamatergic, GABAergic and autophagic pathways. There may also be co-incident dysregulation of the global anti-oxidant network, the endogenous digitalis system, the vasopressin signalling and the hypothalamo-pituitary-adrenal axis. Nuclear factor-kappa B (NF-kappa B) signaling and reactive oxygen species lead to activation of the mammalian target of rapamycin complex I (mTORCI) and this process may be central to the aetiopathogenesis of drug addiction, obesity, foetal programming, diabetes mellitus, epilepsy and bipolar disorder. Antiglycaemics such as cannabinoid CB2 agonists, metformin, artesunate and valproate; insulin-mimetics such as glucagon-like peptide-I (GLP-I) and its analogues; phytomedicines from garlic and curcumin are now shown to exhibit neuroprotective effects. These agents which may down-regulate inflammatory cytokines, upregulate endothelial nitric oxide (eNOS) and peroxisome proliferator-activated receptor alpha (PPAR-α) signalling, attenuate mitochondrial dysfunction, enhance the actions of glucagon-like peptide-I (GLP-I), inhibit mTOR, NF-kappa B, interleukin-I β and glycogen synthase kinase-3 β stand to be of benefit in these illnesses which demonstrate considerable overlay in their aetopathogenic mechanisms. Underpinnings and bidirectional relationships between the metabolic syndrome and mental health disorders may pave way for common new fronts to drug development in translational cardiovascular psychiatry and neurology.

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Section: Type 2 Diabetes Mellitus Drug Addiction Bipolar Disorder Asupporting

confidence: 80%

Section: Type 2 Diabetes Mellitus Drug Addiction Bipolar Disorder Asupporting

confidence: 49%

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Oriaifo¹

2015

J. Med. Med. Sci

View full text Add to dashboard Cite

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“…Pentylenetetrazol-kindling causes excitotoxicity by the excessive generation of ROS and RNS (reactive nitrogen species) [39,44]. In the present study, PTZ-kindling significantly increased oxidative damage as evidenced by the increase in malondialdehyde and in nitrite concentration, and by the depletion of endogenous antioxidant defense enzyme-reduced glutathione activity in the cortex and subcortical regions.…”

Section: Discussionmentioning

confidence: 90%

Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats

Soni

Koushal

Reddy

et al. 2015

Epilepsy & Behavior

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“…Recent animal studies have further demonstrated that long‐term metformin pretreatment can obviously alleviate the damage of ischemic stroke to brain tissue 12, 13, 14. In addition, metformin is also effective in treating global cerebral ischemia,15 intracerebral hemorrhage,16 epilepsy,17 Parkinson disease,18, 19 and Huntington disease 20. However, whether and how metformin treatment is effective in reducing brain injury after CA remain uninvestigated.…”

Section: Introductionmentioning

confidence: 99%

Metformin Improves Neurologic Outcome Via AMP‐Activated Protein Kinase–Mediated Autophagy Activation in a Rat Model of Cardiac Arrest and Resuscitation

Zhu

Liu

Huang

et al. 2018

JAHA

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BackgroundSudden cardiac arrest (CA) often results in severe injury to the brain, and neuroprotection after CA has proved to be difficult to achieve. Herein, we sought to investigate the effects of metformin pretreatment on brain injury secondary to CA and cardiopulmonary resuscitation.Methods and ResultsRats were subjected to 9‐minute asphyxial CA after receiving daily metformin treatment for 2 weeks. Survival rate, neurologic deficit scores, neuronal loss, AMP‐activated protein kinase (AMPK), and autophagy activation were assessed at indicated time points within the first 7 days after return of spontaneous circulation. Our results showed that metformin pretreatment elevated the 7‐day survival rate from 55% to 85% and significantly reduced neurologic deficit scores. Moreover, metformin ameliorated CA‐induced neuronal degeneration and glial activation in the hippocampal CA1 region, which was accompanied by augmented AMPK phosphorylation and autophagy activation in affected neuronal tissue. Inhibition of AMPK or autophagy with pharmacological inhibitors abolished metformin‐afforded neuroprotection, and augmented autophagy induction by metformin treatment appeared downstream of AMPK activation.ConclusionsTaken together, our data demonstrate, for the first time, that metformin confers neuroprotection against ischemic brain injury after CA/cardiopulmonary resuscitation by augmenting AMPK‐dependent autophagy activation.

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Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice

Cited by 104 publications

References 26 publications

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats

Metformin Improves Neurologic Outcome Via AMP‐Activated Protein Kinase–Mediated Autophagy Activation in a Rat Model of Cardiac Arrest and Resuscitation

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