Effects of maternal social isolation on adult rodent offspring cognition

Abstract

Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus–response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress.

The transgenerational consequences of paternal social isolation and predation exposure in threespined sticklebacks

“…The effect size of paternal isolation on offspring survival was moderate and biologically meaningful, with offspring captured, on average, over three times faster when their father was isolated compared to when he had a neighbor. These maladaptive effects are consistent with a previous study in rats, where offspring of socially-isolated mothers showed cognitive impairments and increased anxiety-like behaviors (McDonald et al . 2023).…”

“…Here, we demonstrate that social isolation in adult males does not just affect individuals within a lifetime, but also has detrimental consequences for offspring, leading to lower survival against a predator. This may arise because ancestral stress can make offspring more vulnerable to stress by reprograming the HPA axis, hampering offspring ability to respond appropriately to stress encountered within their own lifetime (Yehuda et al 2008;Rodgers et al 2013;Faraji et al 2017;McDonald et al 2023). Although no studies (to our knowledge) have looked at the transgenerational consequences of paternal isolation prior to fertilization, our results are consistent with previous studies demonstrating that other forms of paternal social stress, including maternal separation early in life (Gapp et al 2014), social defeat (Dietz et al 2011), and social instability (Kong et al 2021), alter offspring anxiety and corticosterone levels.…”

“…The mechanism by which paternal social isolation affects offspring is unknown, but is clearly different than mechanisms of maternal social isolation, largely because those maternal social effects seem to be passed down via glucocorticoids in eggs or during gestation (Walsh et al 2019;MacLeod et al 2023;McDonald et al 2023). Dietz et al (2011) found that paternal social defeat in mice increased offspring susceptibility to depression and anxiety-like behaviors, but that this effect was largely not present when offspring were generated via IVF, suggesting that these transgenerational effects were mediated by changes in maternal investment in her offspring in response to perceived paternal quality (acquired during behavioral interactions between the mother and father).…”

“…2013; Faraji et al . 2017; McDonald et al . 2023), thus potentially leading to maladaptive behaviors in stressful situations (e.g., predation events (Hellmann et al .…”

“…2019). Similarly, in rats, offspring of socially-isolated mothers showed cognitive impairments and increased anxiety-like behaviors (McDonald et al . 2023).…”