Involvement of H₂S, NO and BDNF‐TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole‐induced kindling and cognitive impairments in mice

Abstract

Cognitive impairments are frequently observed in epileptic patients, particularly in memory function. 1 Pentylenetetrazole (PTZ) kindling is generally accepted as a chronic experimental animal model of epilepsy. PTZ kindling causes modifications in the molecular and cellular levels, which are responsible for the oxidative stress and neurodegenerative changes in hippocampus 2 and lead to memory dysfunction. 3 Reactive aldehydes, including malondialdehyde (MDA) and 4-hydroxynonena (4-HNE), are the product of lipid peroxidation. The accumulation of such reactive aldehydes not only led to oxidative stress and neuronal death 4 but also resulted in a deterioration of

Beneficial effects of atorvastatin on sex‐specific cognitive impairment induced by a cerebral microhaemorrhage in mice

“…In our model, atorvastatin did not modulate the expression of the synaptic proteins, PSD-95 and synaptophysin. Several hypotheses can be used to explain its pro-cognitive effects:-(i) the BDNF/trkB pathway might regulate the synaptic interactions affecting cognition and memory (Ahmed & Kamel, 2020); (ii) the increase in glucose uptake in the hippocampus might restore synaptic transmission (Lee et al, 2016) and (iii) the favourable cortical microenvironment and the preservation of the cortico-hippocampal network, as outlined above, might be neuroprotective (Cimino et al, 2007). The pro-cognitive effects of atorvastatin appeared to be unrelated to the expression of estrogen receptors, as the latter was not modulated by atorvastatin in males.…”

“…Furthermore, atorvastatin activated the BDNF-trkB pathway at the lesion site. BDNF exhibits neuroprotective effects by binding to its specific receptor trkB but can also regulate synaptic interactions that may affect cognition and memory (Ahmed & Kamel, 2020). According to Fracassi et al (2019), the increase of BDNF induced by statins might be mediated by their action on the mevalonate pathway and/or on independent mechanisms relying on the nuclear receptors peroxisome proliferator-activated receptors alpha (PPARα/NR1C1).…”

“…In our model, atorvastatin did not modulate the expression of the synaptic proteins, PSD-95 and synaptophysin. Several hypotheses can be used to explain its pro-cognitive effects:-(i) the BDNF/trkB pathway might regulate the synaptic interactions affecting cognition and memory (Ahmed & Kamel, 2020); (ii) the increase in glucose uptake in the hippocampus might restore synaptic transmission (Lee et al, 2016) and…”

The Expression and Function of Nitric Oxide Synthase Enzyme in Atorvastatin Effects on Morphine-Induced Dependence in Mice

“…Many studies demonstrated that a variety of cholesterol-independent pleiotropic effects of statins could be mediated through NO/cGMP pathway (27). Accordingly, Moezi et al (20) showed that NO signalling could mediate the anticonvulsant effect of atorvastatin probably through iNOS.…”

Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy

“…One of the major barriers to clearly defining the role of H2S in the brain has been the prior inability to precisely measure H2S concentrations in isolated tissues [34]. While prior reports have indirectly assessed the role of H2S on cognitive function in rodents with chemically-kindled seizures [35], no study has yet quantified the progressive changes in H2S levels in the brains during the kindling process itself. Further, little work has been conducted to establish how acute seizures influence H2S levels in the brain and periphery (i.e.…”