Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

Abstract

BACKGROUND: Alzheimer’s Dementia (AD) cases are increasing with the global elderly population. To study the part of the brain affected by AD, animal models for hippocampal degeneration are still necessary to better understand AD pathogenesis and develop treatment and prevention measures. AIM: This study was a systematic review of toxic substance-induced animal models of AD using the Morris Water Maze method in determining hippocampal-related memory impairment. Our aim was reviewing the methods of AD induction using toxic substances in laboratory rodents and evaluating the report of the AD biomarkers reported in the models. METHODS: Data were obtained from articles in the PubMed database, then compiled, categorized, and analyzed. Eighty studies published in the past 5 years were included for analysis. RESULTS AND DISCUSSION: The most widely used method was intracerebroventricular injection of amyloid-β _substances. However, some less technically challenging techniques using oral or intraperitoneal administration of other toxic substances also produce successful models. Instead of hippocampal neurodegeneration, many studies detected biomarkers of the AD pathological process while some reported inflammation, oxidative stress, neurotrophic factors, and changes of cholinergic activity. Female animals were underrepresented despite a high incidence of AD in women. CONCLUSION: Toxic substances may be used to develop AD animal models characterized with appropriate AD pathological markers. Characterization of methods with the most easy-handling techniques and more studies in female animal models should be encouraged.

Subchronic Administration of High-dose Monosodium Glutamate Causes Spatial Memory Dysfunction and Structural Deficits of Rat Hippocampus

“…A systematic review showed that MSG, aluminum chloride, high salt-cholesterol diet caused toxic-substance-induced hippocampal degeneration. Most of those reviewed-studies (52 studies) evaluated neurodegenerative markers including synaptic damage, cytoplasmic swelling, pyknotic nuclei, vacuolization, and hippocampal neuronal shrinkage (27). It also confirmed the presences of apoptosis molecular markers such as Caspase-3, B-cell associated X-protein, B-cell lymphoma protein-2, fluoro jade, and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and neuroglial responses (microtubule associated protein-2, glial fibrillary acidic protein, neuronal nuclei, ionized calcium-binding adaptor molecule-1) (27).…”

Colonic Myenteric Plexus Neurodegeneration and Minor Colon Inflammation in Trimethyltin-induced Rat Model of Neurodegeneration

“…All rats were sacrificed on day 28 after TMT injection. 15,19 Under ketamine anesthesia (100 mg/kg body weight, intramuscular), transcardial perfusion with phosphate-buffered saline (PBS) was performed. The whole colon was excised, and its length was measured (Fig.…”

“…Rats in the TMT group were given a single intraperitoneal injection of TMT (8 mg/kg body weight). 15,19 The animals were excluded if they died prematurely. All animal experiments followed a protocol approved by the Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada (reference number: KE/FK/0897/ EC/2019).…”

“…10,18 This model of hippocampal neurodegeneration has been utilized because of its short duration and simple technique. 19 Thus, TMT-induced rat is considered a valuable tool for studying the molecular mechanisms of neurodegenerative diseases. However, no findings have been reported on the effect of TMT on ENS and its possible involvement in the CNS degeneration observed in the TMT-induced rat model of neurodegeneration.…”