Abstract
Trimethyltin (TMT) is an organotin compound with potent neurotoxic action characterized by neuronal degeneration in the hippocampus. This study evaluated the protective effects of a Scolopendra water extract (SWE) against TMT intoxication in hippocampal neurons, using both in vitro and in vivo model systems. Specifically, we examined the actions of SWE on TMT- (5 mM) induced cytotoxicity in primary cultures of mouse hippocampal neurons (7 days in vitro) and the effects of SWE on hippocampal degeneration in adult TMT- (2.6 mg/kg, intraperitoneal) treated C57BL/6 mice. We found that SWE pretreatment (0–100 μg/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, as determined by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that perioral administration of SWE (5 mg/kg), from −6 to 0 days before TMT injection, significantly attenuated hippocampal cell degeneration and seizures in adult mice. Furthermore, quantitative analysis of Iba-1 (Allograft inflammatory factor 1)- and GFAP (Glial fibrillary acidic protein)-immunostained cells revealed a significant reduction in the levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus (DG) of mice treated with SWE prior to TMT injection. These data indicated that SWE pretreatment significantly protected the hippocampus against the massive activation of microglia and astrocytes elicited by TMT. In addition, our data showed that the SWE-induced reduction of immune cell activation was linked to a significant reduction in cell death and a significant improvement in TMT-induced seizure behavior. Thus, we conclude that SWE ameliorated the detrimental effects of TMT toxicity on hippocampal neurons, both in vivo and in vitro. Altogether, our findings hint at a promising pharmacotherapeutic use of SWE in hippocampal degeneration and dysfunction.
Highlights
Centipedes, especially Scolopendra subspinipes (Leach, William, 1815) and Scolopendra subspinipes mutilans (syntype NHMW (Naturhistorisches Museum Wien) of S. mulitans Koch, 1878), have been used in oriental medicine to treat neuroinflammatory conditions including spastic diseases such as spasms, Brain Sci. 2019, 9, 369; doi:10.3390/brainsci9120369 www.mdpi.com/journal/brainsciBrain Sci. 2019, 9, 369 childhood convulsions, and seizures [1,2,3]
TMT administration induces severe hippocampal damage and consequent behavioral alterations such as ataxia, aggression, tail mutilation, vocalization, and seizures [11,12]. These behavioral features mimic those of individuals occupationally or accidentally exposed to TMT, and the similar temporal correlation between the time of cell death and the onset of the seizure behavior may suggest a causal relationship between
Epilepsy has been linked to increased levels of inflammatory mediators in the brain, and brain inflammation might contribute to the onset and perpetuation of mediators in the brain, and brain inflammation might contribute to the onset and perpetuation of seizures in a variety of epilepsies
Summary
Centipedes, especially Scolopendra subspinipes (Leach, William, 1815) and Scolopendra subspinipes mutilans (syntype NHMW (Naturhistorisches Museum Wien) of S. mulitans Koch, 1878), have been used in oriental medicine to treat neuroinflammatory conditions including spastic diseases such as spasms, Brain Sci. 2019, 9, 369; doi:10.3390/brainsci9120369 www.mdpi.com/journal/brainsciBrain Sci. 2019, 9, 369 childhood convulsions, and seizures [1,2,3]. Scolopendra pharmacopuncture is typically used to treat entrapment neuropathies and convulsive diseases [6]; no study to date has examined the therapeutic effects of SWE using a seizure model. TMT administration induces severe hippocampal damage and consequent behavioral alterations such as ataxia, aggression, tail mutilation, vocalization, and seizures [11,12]. These behavioral features mimic those of individuals occupationally or accidentally exposed to TMT, and the similar temporal correlation between the time of cell death and the onset of the seizure behavior may suggest a causal relationship between
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