IntelliCage Automated Behavioral Phenotyping Reveals Behavior Deficits in the 3xTg-AD Mouse Model of Alzheimer’s Disease Associated With Brain Weight

Abstract

Transgenic rodent models of Alzheimer’s disease (AD) were designed to study mechanisms of pathogenesis and connect these mechanisms with cognitive decline. Measurements of cognition in rodents can be confounded, however, by human handling and interaction; the IntelliCage was created to circumvent these issues while measuring various facets of cognition in a social environment with water consumption as the primary motivator for task completion. Here, for the first time, we examined the behavioral performance of 3xTg-AD mice in the IntelliCage. Seven- to 9-month-old female 3xTg-AD and non-transgenic (NonTg) mice were tested for 29 days in the IntelliCage to measure prefrontal cortical and hippocampal function. We found that a higher percentage of NonTg mice (86.96%) were able to successfully complete the training (adaptation) phases compared to their 3xTg-AD (57.14%) counterparts. Furthermore, the 3xTg-AD mice showed impairments in attention and working memory. Interestingly, we found that differences in body and brain weight between NonTg and 3xTg-AD mice were associated with whether mice were able to complete the IntelliCage tasks. 3xTg-AD mice that completed IntelliCage tasks had lower cortical insoluble amyloid-β40 fractions than their 3xTg-AD counterparts who failed to complete the tasks. Collectively, these results demonstrate deficits in cognition in the 3xTg-AD mouse and inform scientists of important factors to consider when testing this transgenic model in the IntelliCage.

Temporal and brain region‐specific elevations of soluble Amyloid‐β40‐42 in the Ts65Dn mouse model of Down syndrome and Alzheimer’s disease

“…The homogenized tissues were centrifuged at 4 °C for 30 min, and the supernatant (soluble fraction) was stored at −80 °C. Soluble fractions of mouse Aβ 40 and Aβ 42 in the homogenates were detected using the commercially available ELISA kits (Invitrogen‐Thermo Fisher Scientific KMB3481 and KMB3441, respectively) as previously described (Winslow et al, 2021). All samples were run in duplicate wells.…”

“…All samples were run in duplicate wells. For immunoblotting, 30 μg of total protein from the regional homogenates was separated under reducing conditions and blotted as previously detailed (Winslow et al, 2021). The following Invitrogen antibodies were purchased and used: APP (Dilution 1:500, Catalog #14‐9749–82), β‐Actin (Dilution 1:5,000, Catalog #PA116889).…”

“…3N founder dams were purchased in 2019 from Jackson Laboratory. Subsequently, the the commercially available ELISA kits (Invitrogen-Thermo Fisher Scientific KMB3481 and KMB3441, respectively) as previously described (Winslow et al, 2021). All samples were run in duplicate wells.…”

Neutrophil modulation of behavior and cognition in health and disease: The unexplored role of an innate immune cell

“…Currently, this system is mostly used with rodent models of psychiatric disorders, including substance abuse. There have been a few studies that have used it to characterize behavioral changes in animal models of neurodegeneration 60,61 . Very few studies have however used this model to look at the effect of inflammation on behavior.…”

“…There have been a few studies that have used it to characterize behavioral changes in animal models of neurodegeneration. 60 , 61 Very few studies have however used this model to look at the effect of inflammation on behavior. Indeed, I found only one article that looked at the effect of neutrophil manipulation on the behavioral outcome using the IntelliCage.…”