The impact of environmental factors during maternal separation on the behaviors of adolescent C57BL/6 mice

Abstract

Neonatal maternal separation is a widely used method to construct an early-life stress model in rodents. In this method, pups are separated from their mothers for several hours every day during the first 2 weeks of life, which results in adverse early-life events. It is a known fact that maternal separation can exert a significant impact on the behavior and psychological health, such as anxiety and depression, in adolescent offspring. However, environmental conditions during maternal separation can differ such as the presence of other animals or by placing pups in a different dam. To investigate the differential effects of various conditions of maternal separation on the behavior of adolescent mice, we created the following groups: (1) iMS group: pups were moved to an isolated room with no other adult mice in a nearby cage, (2) eDam group: the pups randomly exchanged their dams, (3) OF group: pups were shifted to another cage with the bedding material containing maternal odor (olfactory stimulation), and (4) MS group: pups were shifted to another vivarium. From postnatal day (PND) 2–20 (i.e., 19 consecutive days), pups were separated from the dam daily for 4 h and exposed to various environments (MS, iMS, eDam, and OF) or were left undisturbed [control (CON) group]. A series of behavioral assessments were conducted to evaluate locomotion, anxiety, recognition, learning, and memory in adolescent offspring. The results showed that neonatal maternal separation led to impaired recognition memory, motor coordination, and motor skill learning across all groups. However, the iMS group exhibited anxiety-like behavior in the elevated plus maze test and enhanced the extinction of fear memory in the auditory fear conditioning test. The OF and eDam groups displayed partially recovered short-term working memory in the Y-maze test but exhibited opposite exploratory behaviors. The OF group spent more time in the center, while the eDam group spent less time. These findings demonstrated that exposure to different environmental conditions during maternal separation causes behavioral alterations in adolescent offspring, providing a potential explanation for the variation in behavioral phenotypes observed in the early-life stress models.

Nature and nurture: Comparing mouse behavior in classic versus revised anxiety‐like and social behavioral assays in genetically or environmentally defined groups

“…Like numerous prior studies, we found anxiety‐like behavior assayed by the EPM to depend upon both genetic 24 , 25 , 26 and environmental 27 , 28 , 29 , 30 factors. Relative to B6 mice, BALB and 129S6 mice, two isogenic mouse strains widely used to model heightened anxiety‐like behavior, exhibited less time spent in the open arms as well as more time spent in the closed arms of the EPM.…”

“…Like numerous prior studies, we found anxiety-like behavior assayed by the EPM to depend upon both genetic [24][25][26] and environmental [27][28][29][30] factors. Relative to B6 mice, BALB and 129S6 mice, two isogenic females to a greater extent than males.…”

Nature and nurture: comparing mouse behavior in classic versus revised anxiety-like and social behavioral assays in genetically or environmentally defined groups

“…Finally, exposure to multiple assays augmented sociability, likely accounting for the lack of MSEW-induced social motivation deficits that we have previously reported. 13,17 Assessing anxiety-like behavior using classic assays: EPM and OFT Like numerous prior studies, we found anxiety-like behavior assayed by the EPM to depend upon both genetic [19][20][21] and environmental [22][23][24][25] factors. Relative to B6 mice, BALB and 129S6 mice, two isogenic mouse strains widely used to model heightened anxiety-like behavior, exhibited less time spent in the open arms as well as more time spent in the closed arms of the EPM.…”

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice

“…Early adverse life experience during neurodevelopmental periods is a well-recognized risk factor for several psychiatric disorders. , One consistent consequence of ELS is cognitive deficits. − Previous studies have found that mice subjected to ELS exhibit substantial cognitive impairment in hippocampus-dependent learning and memory tasks, such as the spatial object recognition test, compared to the controls. − Therefore, the ELS animal model has been valuable for investigating treatments targeting cognitive deficits in psychiatric disorders. In this study, we examined the cognitive impairment in MS mice through behavioral tests.…”