The three sisters of fate: Genetics, pathophysiology and outcomes of animal models of neurodegenerative diseases. (April 2022)

• Record Type: Journal Article
• Authors: Klonarakis, Michael; De Vos, Maya; Woo, Emma K.; Ralph, Liam T.; Thacker, Jonathan S.; Gil-Mohapel, Joana
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 135(2022)
• Publication Date: 2022-04
• Subjects: Alzheimer's disease -- Behavioural changes -- Cognitive impairment -- Huntington's disease -- Lesion models -- Motor impairment -- Neuropathology -- Parkinson's disease -- Rodent models -- Transgenic models -- Toxin-induced models; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2022.104541
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Animal models are used to study how neuronal dysfunction causes abnormal behaviours. Animal models are also used to test the efficacy of therapeutic approaches. Genetic animal models differ in the genetic construct used and its expression level. Toxin-induced lesion models differ in the toxin used and the brain region lesioned. The degree to which animal models mimic pathological and behavioral deficits varies. Abstract: Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are neurodegenerative disorders characterized by progressive structural and functional loss of specific neuronal populations, protein aggregation, an insidious adult onset, and chronic progression. Modeling AD, PD, and HD in animal models is useful for studying the relationship between neuronal dysfunction and abnormal behaviours. Animal models are also excellent tools to test therapeutic approaches. Numerous genetic and toxin-induced models have been generated to replicate these neurodegenerative disorders. These differ in the genetic manipulation employed or the toxin used and the brain region lesioned, and in the extent to which they mimic the neuropathological and behavioral deficits seen in the corresponding human condition. Each model exhibits unique advantages and drawbacks. Here we present a comprehensive overview of the numerous AD, PD, and HD animal models currently available, with a focus on their utilities and limitations. Differences among models might underlie some of the discrepancies encountered in the literature and should be taken into consideration when designing new studies and testing putative therapies.