Characteristics of Scopolamine- and Trimethyltin-Induced Models of Alzheimer’s Disease

Abstract

Alzheimer's disease is the most common form of dementia and a global problem that is becoming increasingly serious. Worldwide, about 50 million people live with dementia, and, according to forecasts, by 2050 this number will increase to 135-152 million. Description of different schemes of administration of trimethyltin and scopolamine for induction of morphological signs of Alzheimer 's-like dementia and characterization of molecular changes in these types of experimental dementias. More than 55 literature sources on the topic of this scientific work were analyzed. Review and experimental scientific articles from the Google Academy and PubMed databases were used for the analysis. Scopolamine is a muscarinic receptor antagonist that inhibits/blocks cholinergic transmission of acetylcholine by competitively antagonizing muscarinic receptors. In this type of experimental dementia, dysregulation of the cholinergic system has been reported with decreased levels of acetylcholine and decreased levels of other neurotransmitters that, in addition to acetylcholine, are involved in memory and learning (glutamate, dopamine, norepinephrine). Scopolamine promotes synaptic dysfunction and leads to oxidative damage to hippocampal tissue with decreased levels of endogenous antioxidant mediators. In rats with scopolamine-induced dementia, higher levels of proinflammatory cytokines in the hippocampus and glial cell activation are observed. Trimethyltin (trimethyltin chloride) belongs to the family of organotin compounds with a neurotoxic effect, causing degeneration of neurons of the CNS in humans and rodents. The pathogenic effects of trimethyltin are common to most neurodegenerative disorders: impaired synaptic plasticity, oxidative stress, mitochondrial damage, intracellular calcium overload and glutamate excitotoxicity, which generally leads to both necrotic and apoptotic death of brain cells. The administration of scopolamine and trimethyltin to experimental animals initiates the appearance of Alzheimer-like morphological features in the brain. The molecular mechanisms of both models are similar and include dysregulation of the cholinergic system of the brain, synaptic and mitochondrial dysfunction, oxidative damage and inflammatory changes in the brain, impaired neurogenesis and activation of apoptosis, etc. Modeling Alzheimer's disease using scopolamine or trimethyltin is effective, technically simple and can be recommended for assessing the effectiveness of new treatments for Alzheimer's disease at the preclinical stage.