Transcriptional Signatures of Cognitive Impairment in Rat Exposed to Prenatal Stress
Exposure to adverse events during gestation has detrimental effects on the maturation of specific brain networks, triggering changes in the expression of several stress-related mechanisms that may lead to long-lasting functional consequences, including cognitive deterioration. On these bases, the aim of the present study was to investigate the effects of early-life stress exposure on cognition and to explore potential molecular mechanisms contributing to the long-term functional impairment. We found that exposure to prenatal stress, a well-established animal model of early-life adversity, produces a significant disruption in the novel object recognition test both in male and female adult rats, although such impairment was more pronounced in females. Furthermore, the cognitive dysfunction observed during the behavioral test appears to be sustained by a disrupted activation of key networks of genes that may be required for proper cognitive performance. In particular, within the dorsal hippocampus, a brain region critical for cognition, the glucocorticoid, the inflammatory, and the protein kinase A signaling pathways are regulated by the novel object recognition test in an opposite manner in animals previously exposed to prenatal stress, when compared with control animals. These data further support the evidence that early-life stress exposure prompts cognitive impairment and suggest that this is the consequence of inability to activate the proper transcriptional machinery required for the cognitive performance.
KeywordsPrenatal stress Cognitive impairment Dorsal hippocampus Transcriptional signature
We thank Francesca Calabrese for her contribution in the initial part of the work.
This work has been supported by the Italian Ministry of Instruction, University and Research (PRIN grant number 2015SKN9YT), Fondazione CARIPLO (grant number 2012-0503), and European Union/NEURON-ERANET to M.A.R. Moreover, A.C. received support from Ricerca Corrente (Ministry of Health) and from a NEURON-ERANET grant.
Compliance with Ethical Standards
All animal experiments were conducted according to the authorization from the Health Ministry n. 295/2012-A (20/12/2012), in full accordance with the Italian legislation on animal experimentation (Decreto Legislativo 116/92) and adherent to EU recommendation (EEC Council Directive 86/609), in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals.
All efforts were made to minimize animal suffering and reduce the total number of animals used, while maintaining statistically valid group numbers.
Conflict of Interest
The author M.A.R. has received compensation as speaker/consultant from Lundbeck, Otzuka, Dainippon Sumitomo Pharma, and Sunovion, and he has received research grants from Lundbeck, Dainippon Sumitomo Pharma, and Sunovion. All the other authors declare that they have no financial interest or potential conflicts of interest.
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