Nutritional stress timing differentially programs cognitive abilities in young adult male mice

ABSTRACT

Objectives: The impact of chronic exposure to environmental adversities on brain regions involved in cognition and mental health depends on whether it occurs during the perinatal period, childhood, adolescence or adulthood. The effects of these adversities on the brain and behavior arise as a function of the timing of the exposure and their co-occurrence with the development of specific regions. Here we aimed to explore the behavioral phenotypes derived from two nutritional stress paradigms which differed in the timing of exposure: a low-protein perinatal diet during gestation and lactation and a low-protein diet during adolescence.

Methods: Locomotor and exploratory activity, recognition memory and aversive memory were measured in CF-1 8-week-old male mice subjected to perinatal malnutrition (LP-P) or adolescent malnutrition (LP-A), and their respective controls with normal protein diet (NP-P and NP-A).

Results: By using the open field test, we found that LP-P and LP-A mice showed reduced exploratory activity compared to controls, but no alterations in their locomotor activity. Recognition memory was impaired only in LP-P mice. Interestingly, aversive memory was not altered in LP-P mice but was enhanced in LP-A mice. Considering the stress-inoculation theory, we hypothesized that protein malnutrition during adolescence represents a challenging but still moderate stressful environment, which promotes active coping in face of later adversity.

Conclusion: Our results indicate that while perinatal malnutrition impairs recognition memory, adolescent malnutrition enhances aversive memory, showing dissimilar adaptive responses.

KEYWORDS:

• Early-life stress
• adolescent stress‌
• low-protein malnutrition
• malnourishment‌
• exploratory activity‌
• recognition memory
• aversive memory
• hippocampus
• prefrontal cortex

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Agencia Nacional de Promoción Científica y Tecnológica under grant numbers PICT-2013-0653 (to ETC) and PICT 2015–0975 (to LMI); Fondo para la Investigación Científica y Tecnológica, Secretaría de Ciencia y Técnica, Universidad de Buenos Aires (UBA) under grant numbers 20020130100011BA (to ETC) and 20020170100656BA (to LMI); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) under grant numbers PIP-476 (to ETC) and PIP-0186 (to LMI).

Notes on contributors

Bruno G. Berardino

Bruno G. Berardino, I am a postdoc researcher (CONICET fellow) studying the effects of early-life adversities in the development of mental health disorders and the mediation of epigenetic mechanisms in the incorporation of those experiences into the brain. This project arises from previous studies at Dr. Eduardo T. Cánepa’s lab in which we proposed to study the causes of the persistence throughout life of cognitive deficiencies originated in adverse events occurred at early stages of the development in a perinatal malnutrition mouse model. I obtained a Biological Sciences degree with an orientation in molecular biology from the University of Buenos Aires. During my PhD (CONICET fellow), also from the University of Buenos Aires, I studied the role of microRNAs in the establishment of behavioral effects derived from a perinatal malnutrition mice model. During this period, I obtained a Fulbright scholarship to analyze oligodendrocyte morphology in Gabriel Corfas’ lab at Boston Children’s Hospital (Harvard University). Actually, I successfully administer a research project (staffing and budget), collaborate with other researchers, and produce peer-reviewed publications. In addition, I am a Teaching Assistant in Molecular Biology (University of Buenos Aires) and participate in community-based activities related to scientific communication.

Fabricio Ballarini

Fabricio Ballarini, I am a career investigator at the National Council for Scientific and Technological Research (CONICET) of Argentina since 2015 at Laboratory of Memory, directed by Haydee Viola at the University of Buenos Aires (UBA) School of Sciences. I graduated as BsC in Biological Science in the University of Buenos Aires (UBA). The main research focus of my laboratory is learning and memory in human.

Mariela Chertoff

Mariela Chertoff, I am a Research assistant at the National Council for Scientific and Technological Research (CONICET) of Argentina since 2015 at Laboratory of Neuroepigenetics, directed by Eduardo Cánepa located at the University of Buenos Aires (UBA) School of Sciences. My project is focused on the effect of perinatal adversities on brain development and the epigenetic mechanisms, mainly DNA methylation. I graduated as Licenciada (equivalent to a BsC) in Biological Sciences in 2003 (UBA). I obtained my PhD in Neuroscience from UBA (2009) and I was a Marie Curie International incoming fellow at the Institute of Neuroscience, Autonomous University of Barcelona Spain (2011-2013). I administer several grants, codirect a PhD thesis, collaborate with the Neuroepigenetics Laboratory of Dr Reid Alisch at University of Wisconsin, USA. Additionally, I am Teacher at Molecular Biology and participate in community-based activities related to scientific communication.

Lionel M. Igaz

Lionel M. Igaz, I am a career Investigator (PI) at the National Council for Scientific and Technological Research (CONICET) of Argentina, and since 2010, Director of the Neuronal Physiopathology Laboratory, Institute Houssay for Physiology and Biophysics (IFIBIO-Houssay) – CONICET, located at the University of Buenos Aires (UBA) School of Medicine (Buenos Aires, Argentina). I graduated as Licenciado (equivalent to a BsC) in Biological Sciences in 2000 (UBA). I obtained my PhD in Neuroscience from UBA (2005) and was a postdoctoral fellow at the Center for Neurodegenerative Research (CNDR) at the University of Pennsylvania, USA (2006-2010). The main research focus of my laboratory is the pathobiology of neurodegenerative diseases.

Eduardo T. Cánepa

Eduardo T. Cánepa, I am an Associate Professor and Principal Researcher at and Head of the School of Exact and Natural Sciences of the University of Buenos Aires, and head of the Neuroepigenetics group. My research project is aimed to investigate the molecular causes of the persistence throughout life of cognitive deficiencies derived from protein malnutrition during critical periods of development and maturation of the brain. This issue is of huge importance because it involves the problem of malnutrition, which is present in large parts of the population of our country and affects mainly the poorer sectors of the population. I have extensive training in Molecular Biology and Neurobiology as well as in key research areas.