Behavioral and cognitive impact of early life stress: Insights from an animal model

Abstract

Background Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. Objective The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. Methods We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. Results Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, “suscep tible”: with depression-like behavior and “resilient”: without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression-like phenotype was evident only later on at PND90. Conclusions Our findings suggest that early life stress caused co-occurrence of anxiety and depression-like behavior at PND32 (mimics human early-adolescent period). This co-occurrence was lost at PND60 with demonstration of anxiety- but not depression-like behavior. Later, depression but not anxiety-like behavior was observed at PND90. It seems that behavioral adaptations occur at the critical PND60 stage (mimics human late-adolescent period), where behavioral and cognitive switching occurs, thereby, expressing susceptible and resilient phenotypes.

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

“…Our findings revealed that, as expected, MS led to impaired working memory and reference memory in 8-RAM considering the number of total errors committed along all testing days. This result is consistent with prior studies showing that different ELS models can disrupt working memory and memory processes (i.e., consolidation and retrieval processes), through functional alterations of specific brain regions (Cattaneo et al, 2019;Chocyk et al, 2013;de Azeredo et al, 2017;Grassi-Oliveira et al, 2016;Jin et al, 2013;van der Kooij, Grosse, Zanoletti, Papilloud, & Sandi, 2015;Liu, Atrooz, Salvi, & Salim, 2017;Mehta & Schmauss, 2011). However, not all MS animals presented the same pattern of cognitive performance.…”

Behavioral effects of early life maternal trauma witness in rats

“…Body weight, food and water intake were recorded from the beginning of social defeat procedure to the end of behavioral assessments. Trauma witnessing paradigm lasted 7 days, depression- and anxiety-like behavior tests were conducted 24 h later, maintaining a gao of 24 rest in between tests, as published (4,6) . Cognitive functions including short-term and long-term memory tests using radial arm water maze (RAWM) paradigm were performed as published (4,6) .…”

“…Recently, we reported that rats witnessing traumatic events (social defeat of a cage-mate) exhibited severe behavioral deficits resembling post-traumatic stress disorder (PTSD)-like behaviors (4,5) . More recently, we published that early life stress in pups caused later life behavioral deficits in rats (6) . In the present study, by combining the two approaches, we examined later life effect of early life maternal witness stress in rats.…”

Rodent models of post-traumatic stress disorder: behavioral assessment

“…Although age effects on SPS susceptibility have not been evaluated to date, maternal separation was found to strengthen adult SPS-induced increases in anxiety and contextual fear 53 . Early life exposure to SPS caused anxiety-like and depression-like behavior at postnatal day 32 (human early-adolescence), anxiety-like behavior at postnatal day 60 (human late-adolescence), followed by depression-like behavior (stress-susceptible) or no behavioral deficits (stress-resilient) at postnatal day 90 (human adulthood), suggesting that adaptations such as behavioral and cognitive switching occur at postnatal day 60 54 . The two studies of sex differences in fear extinction retention following SPS report conflicting results, with one observing no effect 55 and the other noting deficits 56 .…”

“…Cued reminder 286 Conditioned taste aversion, OF, EPM, elevated T-maze, LDB, cliff avoidance 53,54,[287][288][289][290] NOR, FCFE, RAWM, MWM 51,52,54,291,292 Three-chamber sociability and social novelty test, flinch-jump, hot-plate, SP, FST, von Frey 53,287,[292][293][294] ASR, MB 295,296 Set-shifting 273 EEG, EMG 297 >Month 54,289,293 Social defeat stress Resident-intruder social defeat Contextual reminder 20 EPM, LDB, EZM 72,73,298 Response bias probabilistic reward task, MWM, Barnes maze, step-through inhibitory avoidance, FCFE, RAWM, NOR, Y-maze recognition memory test, Tmaze continuous alteration task [299][300][301][302][303][304][305][306] SPAT, three-chamber sociability test, intracranial self-stimulation, SAAT, SP, FST, OF, tail suspension, olfactory habituationdishabituation 76,264,266,307- Predator scent stress Contextual reminder 111,119,319 EPM, territory discrimination, LDB, OF, hole board 112,116,129,320,…”