Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice.
Giulia Costa, Marcello Serra, Riccardo Maccioni, Maria Antonietta Casu, Sanjay B Kasture, Elio Acquas, Micaela Morelli
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2023 Peer reviewed DOI: 10.1016/j.biopha.2023.114475 via PubMed
Summary
A standardized extract of Withania somnifera (WSE) administered acutely with MDMA counteracted neurotoxic effects in mice, including the loss of dopaminergic neurons and gliosis, as well as improved memory performance. Mice treated with MDMA alone showed decreased TH-positive neurons, increased gliosis, elevated body temperature, and impaired memory, while those given WSE plus MDMA did not exhibit these negative changes compared to MDMA alone. However, WSE pretreatment did not provide protective effects.
Study at a glance
| Design | experimental study |
|---|---|
| Population | mice |
| Key finding | Acute administration of WSE with MDMA protects against neurotoxic effects and cognitive impairment caused by MDMA. |
Abstract
Withania somnifera (WS) is utilized in Ayurvedic medicine owing to its central and peripheral beneficial properties. Several studies have accrued indicating that the recreational amphetamine-related drug (+/-)- 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) targets the nigrostriatal dopaminergic system in mice, inducing neurodegeneration and gliosis, causing acute hyperthermia and cognitive impairment. This study aimed to investigate the effect of a standardized extract of W. somnifera (WSE) on MDMA-induced neurotoxicity, neuroinflammation, memory impairment and hyperthermia. Mice received a 3-day pretreatment with vehicle or WSE. Thereafter, vehicle- and WSE-pretreated mice were randomly divided into four groups: saline, WSE, MDMA alone, WSE plus MDMA. Body temperature was recorded throughout treatment, and memory performance was assessed by a novel object recognition (NOR) task at the end of treatment. Thereafter, immunohistochemistry was performed to evaluate in the substantia nigra pars compacta (SNc) and striatum the levels of tyrosine hydroxylase (TH), as marker of dopaminergic degeneration, and of glial fibrillary acidic protein (GFAP) and TMEM119, as markers of astrogliosis or microgliosis, respectively. MDMA-treated mice showed a decrease in TH-positive neurons and fibers in the SNc and striatum respectively, an increase in gliosis and body temperature, and a decrease in NOR performance, irrespective of vehicle or WSE pretreatment. Acute WSE plus MDMA counteracted the modifications in TH-positive cells in SNc, GFAP-positive cells in striatum, TMEM in both areas and NOR performance, as compared to MDMA alone, while no differences were observed as compared to saline. Results indicate that WSE acutely administered in combination with MDMA, but not as pretreatment, protects mice against the noxious central effects of MDMA.