Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice

Abstract

Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.

Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits

“…Scopolamine is an anticholinergic drug that antagonises cholinergic receptors and impairs hippocampal and prefrontal cortex transmission that deficits learning acquisition [ 10 ]. Intraperitoneal injection of scopolamine also stimulates systemic and consequent neuroinflammation in C57BL/6 mice [ 12 ]. Dioscin (60 mg/kg) treatment for 7 days ameliorated scopolamine-induced deficits in spatial learning memory in mice ( Figure 5 A–C).…”

“…Scopolamine inhibits cholinergic transmission in the hippocampus and prefrontal cortex region, affecting spatial and related learning memory. In this process of neurocognitive impairments, scopolamine increases inflammatory cytokines TNF-α, IL-6 and IL-1β [ 12 ], and enzymes iNOS and COX-2 [ 34 ]. In the animal model of scopolamine, dioscin treatment for 7 days reduced pro-inflammatory mediators, which follows the inhibition of NF-κB phosphorylation.…”

“…Scopolamine is an anticholinergic drug that impairs cognitive functions and learning memory, which resembles molecular and behavioural features of Alzheimer’s disease by impairing cholinergic neurotransmission in the hippocampus and prefrontal cortex [ 10 , 11 ]. In addition, these neuropsychiatric changes also involve the upregulation of pro-inflammatory cytokines and inflammasome components in different brain regions [ 12 ].…”

The Neuroprotective Effect of NEUROMIDE, a Compound Bioidentical to Commensal Bacteria Metabolites

“…After daily oral administration of NEUROMIDE for 4 weeks, a passive avoidance test was performed, and levels of acetylcholine, AchE activity, IL-1β, and TNF-α in the brain were compared with those in the scopolamine-treated group. Scopolamine-treated mice have already been shown to have elevated levels of inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-18) and cognitive impairment [ 35 ].…”

Magnoflorine-Loaded Chitosan Collagen Nanocapsules Ameliorate Cognitive Deficit in Scopolamine-Induced Alzheimer’s Disease-like Conditions in a Rat Model by Downregulating IL-1β, IL-6, TNF-α, and Oxidative Stress and Upregulating Brain-Derived Neurotrophic Factor and DCX Expressions

“…Measurement of Pro-Inflammatory Cytokine Levels. To estimate the pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) in the hippocampus, 54 TNF-α, IL-1β, and IL-6 kits procured from Abbkine Scientific Co., Ltd. were used. The instructions in the manufacturer's protocol were followed, which uses the principle of the sandwich ELISA technique for the evaluation of results.…”