Cuprizone toxicity and Garcinia kola biflavonoid complex activity on hippocampal morphology and neurobehaviour

Abstract

Cuprizone-induced neurotoxicity has been employed to study the biology of remyelination in experimental models of multiple sclerosis. This study was aimed at determining the role of kolaviron, a biflavonoid from Garcinia kola, in mitigating the damaging effects of cuprizone on behaviour and the hippocampus. Twenty-four male albino mice aged 6-8 weeks were categorised into 4 equal groups: Group A (Control) received regular diet; Group B received 200 mg/kg/d of kolaviron in addition to their regular diet; Group C received 0.2% cuprizone diet only, while Group D received both kolaviron and cuprizone diet. The treatment lasted for 35 days after which behavioural tests (Morris water maze, Y maze and open field tests) were conducted and brain tissues were processed for histology, histochemistry (Nissl staining), immunohistochemistry (glial fibrillary acidic protein) and biochemistry (malondialdehyde, superoxide dismutase and glutathione peroxidase). Results showed that cuprizone toxicity led to weight loss, impairment in memory and exploratory drive, oxidative stress, chromatolysis and reactive astrocytosis; meanwhile administration of kolaviron prevented cuprizone-induced weight loss, memory decline, oxidative stress and neuromorphological alterations. In conclusion, administration of kolaviron might be useful in limiting the effects of cuprizone toxicity on the morphology and functions of the hippocampus.

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet

“…A former study demonstrated that CPZ intoxication increases oxidative stress, which in turn triggers apoptosis in mature OLs . This perturbation of the biochemical redox state could lead to neuronal changes and cognitive impairment in CPZ-treated mice and inhibit remyelination . In the present study, the GSH content and GSH-Px activity were nearly twofolds lower in the CPZ + ND group when compared to those in the ND group (Figure A,B; P < 0.001).…”

“…Several antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase are responsible for scavenging cellular ROS. Recent studies have reported that mice exposed to CPZ exhibit enhanced oxidative stress, which is characterized by the decreased activity of GSH-Px and the increased concentration of malondialdehyde (MDA) . Interestingly, KD treatment ameliorated the experimental autoimmune encephalomyelitis (EAE, a murine model for MS)-induced cognitive deficits in mice by attenuating the robust immune response and oxidative stress .…”

“…Recent studies have reported that mice exposed to CPZ exhibit enhanced oxidative stress, which is characterized by the decreased activity of GSH-Px and the increased concentration of malondialdehyde (MDA). 16 Interestingly, KD treatment ameliorated the experimental autoimmune encephalomyelitis (EAE, a murine model for MS)induced cognitive deficits in mice by attenuating the robust immune response and oxidative stress. 17 However, it remains poorly understood whether KD can improve the clinical symptoms and cognitive impairment in CPZ-induced demyelination partly by suppressing oxidative stress.…”

WITHDRAWN: Repurposing of Dapsone as Neuroprotective Agent on Cuprizone-induced Demyelination via Targeting Nrf2 and NF-kB in C57BL/6 Mice

“…In addition, CPZ diet showed neurotoxic effects evidenced by chromatolysis, abnormal Nissl granules, hyperchromatic nuclei and vacuolated neurons in the prefrontal cortex that is also ameliorated by DAP treatment. Previous studies have demonstrated that CPZ administration resulted in prefrontal cortex and hippocampus damage inducing pyknosis, central chromatolysis and cellular fragmentations [43,44]. The changes in the cellular morphology may be linked to the elevation of oxidative stress mediators such as superoxide anion and nitrite ad that can damage neurons and apoptosis [45,46].…”

Ameliorative Effects of Kolaviron on Behavioural Deficits and Oxidative Damage in Prefrontal Cortex and Hippocampus of Cuprizone-Induced Demyelinated Mice

“…Cuprizone-induced neurotoxicity is of immense usefulness in studying the demyelinationremyelination phenomenon associated with multiple sclerosis (MS), due to its characteristic reversibility following withdrawal of the drug (Zendedel et al 2013). Cuprizone is a copper chelating agent often formulated into diet (0.1% -0.5% cuprizone diet) for oral consumption in experimental model and causes oligodendroglial cell death with subsequent demyelination (Silvestroff et al 2012).…”