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. 2020 Dec;127(6):461-476.
doi: 10.1111/bcpt.13457. Epub 2020 Jul 28.

Involvement of H2 S, NO and BDNF-TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole-induced kindling and cognitive impairments in mice

Marwa A Ahmed  1 , Esam O Kamel  2
Affiliations

Involvement of H2 S, NO and BDNF-TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole-induced kindling and cognitive impairments in mice

Marwa A Ahmed et al. Basic Clin Pharmacol Toxicol. 2020 Dec.

Erratum in

Abstract

Cognitive dysfunction was observed in pentylenetetrazole (PTZ)-kindled mice. The potential effectiveness of simvastatin (SIM) on PTZ-induced kindling and cognitive impairments in mice was evaluated. The influence of SIM on hydrogen sulphide (H2 S), nitric oxide (NO), reactive aldehydes and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF-TrkB) signalling was also investigated. Kindling and cognitive impairments in mice were induced by 12 ip injections of PTZ (35 mg/kg) once every alternate day. The levels of reactive aldehydes and nitrite were increased while H2 S was decreased in PTZ-treated mice. These results were accompanied by a reduction in the gene expression of aldehyde dehydrogenase 2, cystathionine β-synthase, BDNF and TrkB. In PTZ-kindled mice, a rise in brain inducible nitric oxide synthase protein expression associated with histopathological changes was observed. SIM administration (1, 5 and 10 mg/kg, daily orally) along with alternate day of PTZ (35 mg/kg) resulted in a decrease in PTZ-induced kindling with a dose-dependent improvement in cognitive function. SIM (10 mg/kg) prevented, to variable extent, the disturbances associated with PTZ-kindled mice with cortical, cerebellar and hippocampal structural improvement. These results suggested that SIM triggers multiple mechanisms that improve cognitive function in PTZ-kindled mice through modulation of oxidative stress, H2 S, NO and BDNF-TrkB signalling pathway.

Keywords: BDNF-TrkB; PTZ-induced kindling; cognitive impairments; gaseous neurotransmitters; simvastatin.

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References

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