Mild cognitive impairment: animal models

Abstract

Mild cognitive impairment (MCI) is an aspect of cognitive aging that is considered to be a transitional state between normal aging and the dementia into which it may convert. Appropriate animal models are necessary in order to understand the pathogenic mechanisms of MCI and develop drugs for its treatment. In this review, we identify the features that should characterize an animal model of MCI, namely old age, subtle memory impairment, mild neuropathological changes, and changes in the cholinergic system, and the age at which these features can be detected in laboratory animals. These features should occur in aging animals with normal motor activity and feeding behavior. The animal models may be middle-aged rats and mice, rats with brain ischemia, transgenic mice overexpressing amyloid precursor protein and presenilin 1 (tested at an early stage), or aging monkeys. Memory deficits can be detected by selecting appropriately difficult behavioral tasks, and the deficits can be associated with neuropathological alterations. The reviewed literature demonstrates that, under certain conditions, these animal species can be considered to be MCI models, and that cognitive impairment in these models responds to drug treatment.

Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory

“…We first explored the effects of vitamin A supplementation and RA treatment on CSD task that allows the detection of early signs of age-related hippocampal-dependent memory deficits ( Chauveau et al, 2010 ; Tronche et al, 2010 ). Studies in middle-aged mice have important implications for the treatment of the non-pathological age-associated cognitive decline, as well as mild cognitive impairment ( Pepeu, 2004 ). The effects of stimulation of retinoid pathway on memory performance have not yet been tested in middle-aged rodents.…”

Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice

“…The main clinical criterion for diagnosing MCI is the observable cognitive loss without being demented [ 4 ]. However, the identification and distinction of MCI from the preclinical phase of AD remain challenging [ 5 ] and impedes the investigation of early pathology. Transgenic animal models that overexpress amyloid-β (Aβ) and presenilin 1 (PS1) are used to study the pathogenesis of AD.…”

“…Transgenic animal models that overexpress amyloid-β (Aβ) and presenilin 1 (PS1) are used to study the pathogenesis of AD. In this model, the severity of damage induced by Aβ, the age of onset, and the severity of memory impairment are key criteria to discriminate MCI from AD [ 5 ]. However, we have a limited understanding of MCI in AD mouse models.…”

Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders

“…All mentioned animal models cause memory deficits that differ in severity and memory type affected (for more information on animal models of memory deficits please see Gallagher, 1997 ; Götz and Götz, 2009 ; More et al, 2016 ; van der Staay et al, 2011 ). They may be a result of impaired cholinergic (scopolamine), glutamatergic (dizocilpine, phencyclidine) or serotonergic neurotransmission (para-chlorophenylalanine), neurons death ( β -amyloid(25–35)-peptide, 192 IgG-saporin, trimethyltin, ibotenic acid, carbon monoxide (CO), brain ischemia, olfactory bulbectomy), oxidative stress (cocaine) or oxidative phosphorylation (prenatal stress) (for more information on animal models of cognitive impairments please see Beraki et al, 2009 ; Cheng et al, 2012 ; Deryabina et al, 2020 ; Li et al, 2020 ; Muriach et al, 2010 ; Nakajima et al, 2007 ; Pepeu, 2004 ; van der Staay et al, 2011 ).…”