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Guevara, Beatriz H.; Céspedes, Ghislaine; Cubeddu, Luigi X.

doi:10.1023/a:1021877512519

Cited by 5 publications

(1 citation statement)

References 19 publications

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“…Overexpression of REST caused repression of ChAT in cholinergic neurons (Lönnerberg et al 1996 ), which could reflect an effect of the upregulated REST levels seen in post-SE animal models. In support of this idea, reduced ChAT activity after kainate injection was observed within hours, and also 6 months later which correlated to seizure severity (Baran et al 2004 ; Guevara et al 2002 ). If REST represses ChAT after seizure this could contribute to cholinergic dysfunction and epileptogenesis.…”

Section: Effects Of Rest In Post Status-epilepticus Seizure Modelsmentioning

confidence: 84%

The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia

Butler-Ryan

Wood

2021

Metab Brain Dis

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Epilepsy is a debilitating neurological disorder characterised by recurrent seizures for which 30% of patients are refractory to current treatments. The genetic and molecular aetiologies behind epilepsy are under investigation with the goal of developing new epilepsy medications. The transcriptional repressor REST (Repressor Element 1-Silencing Transcription factor) is a focus of interest as it is consistently upregulated in epilepsy patients and following brain insult in animal models of epilepsy and ischemia. This review analyses data from different epilepsy models and discusses the contribution of REST to epileptogenesis. We propose that in healthy brains REST acts in a protective manner to homeostatically downregulate increases in excitability, to protect against seizure through downregulation of BDNF (Brain-Derived Neurotrophic Factor) and its receptor, TrkB (Tropomyosin receptor kinase B). However, in epilepsy patients and post-seizure, REST may increase to a larger degree, which allows downregulation of the glutamate receptor subunit GluR2. This leads to AMPA glutamate receptors lacking GluR2 subunits, which have increased permeability to Ca2+, causing excitotoxicity, cell death and seizure. This concept highlights therapeutic potential of REST modulation through gene therapy in epilepsy patients.

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Section: Effects Of Rest In Post Status-epilepticus Seizure Modelsmentioning

confidence: 84%

The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia

Butler-Ryan

Wood

2021

Metab Brain Dis

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Neuroprotection by 7-Nitroindazole Against Iron-Induced Hippocampal Neurotoxicity

Bostanci

Bağirici

2007

Cell Mol Neurobiol

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(1) Iron plays an important role in maintaining normal brain function. In some neurodegenerative disorders including Parkinson's and Alzheimer's disease, iron levels rise in the brain. It is known that higher iron levels induce neuronal hyperactivity and oxidative stress. A body of evidence indicates a relationship between neuronal death and nitric oxide (NO). The aim of present study was to evaluate the effects of NO produced by neuronal nitric oxide synthase (nNOS) on iron-induced neuronal death. (2) Animals were classified into four groups: control, iron, iron+7-nitroindazole, and iron+vehicle. Rats in iron, iron+7-nitroindazole, and iron+vehicle groups received intracerebroventricular (i.c.v.) FeCl3 injection (200 mM, in 2.5 microl). Rats belonging to control groups received the same amount of saline into the cerebral ventricles. All animals were kept alive for 10 days following the operation. Animals in iron+7-nitroindazole group received intraperitoneal 7-nitroindazole (30 mg/kg/day) injections once a day during this period, while the rats belonging to vehicle group received daily intraperitoneal injection of peanut oil. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using the standard histological techniques. (3) The total number of neurons in hippocampus of all rats was estimated with the unbiased stereological techniques. Results of present study show that 7-nitroindazole decreased mean neuron loss from 43% to 11%. Treatment of peanut oil alone did not affect iron-induced hippocampal cell loss with respect to iron group values. (4) Findings of our study suggest that 7-nitroindazole may have neuroprotective effects against iron-induced hippocampal neurotoxicity by inhibiting nNOS.

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7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's disease

et al. 2012

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a b s t r a c tNeuronal nitric oxide synthase (nNOS) is involved in the regulation of diverse intracellular messenger systems in the brain. Nitric Oxide (NO) contributes to inducing signaling cascades that involve a complex pattern of phosphorylation of DARPP-32 (in Thr-34), which controls the phosphoproteins involved in neuronal activation. However, the role of NO in the pathophysiology of Parkinson's disease (PD) and its effect in striatal neurons have been scarcely explored. In the present work, we investigate the effects of a nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI) in the nigrostriatal pathway of striatal 6-hydroxydopamine (6-OHDA) lesioned rats. Our quantitative histological findings show that treatment with 7-NI significantly reduced 6-OHDA-induced dopaminergic damage in the dorsolateral striatum and Substantia Nigra pars compacta (SNpc). Moreover, 6-OHDA lesioned rats show a significant increase of nNOS þ and Phospho-Thr34-DARPP-32 þ cells, accompanied by a consequent decrease of total DARPP-32 þ cells, which suggests an imbalance of NO activity in the DA-depleted striatum, which is also reflected in behavioral studies. Importantly, these effects are reverted in the group treated with 7-NI. These results show a clear link between the state of phosphorylation of DARPP-32 and parkinsonism, which is regulated by nNOS. This new evidence suggests a prominent role for nitric oxide in the neurotransmitter balance within the basal ganglia in the pathophysiology of experimental parkinsonism.

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Untitled

Cited by 5 publications

References 19 publications

The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia

The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia

Neuroprotection by 7-Nitroindazole Against Iron-Induced Hippocampal Neurotoxicity

7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's disease

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