The enduring effect of prenatal protein malnutrition on brain anatomy, physiology and behavior

ABSTRACT

There is increasing evidence that the maternal environment exerts enduring influences on the fetal brain. In response to certain environmental stimuli such as reduced protein content, the fetus changes the course of its brain development, which leads to specific and programed changes in brain anatomy and physiology. These alterations produce a brain with a fundamentally altered organization, which then translates to alterations in adult cognitive function. The effects on brain and behavior may be linked, such that a prenatal stimulus relays a signal to alter brain development and encourage the selection and development of brain circuits and behaviors that would be beneficial for the environment in which the animal was anticipated to emerge. At the same time, the signal would deselect behaviors unlikely to be adaptive. We draw on evidence from rodent models to suggest that the brain that develops after a reduction in protein during the prenatal phase is not uniformly dysfunctional, but simply different. This perspective has implications for the role of prenatal factors in the production and expression of behavior, and may account for the elevation of risk factors for neurological and psychiatric illnesses.

KEYWORDS:

• Prenatal protein malnutrition
• brain
• hippocampus
• prefrontal cortex
• developmental reprograming
• executive function
• attention deficits
• maternal insults
• inhibitory neurons
• neuroplasticity

Acknowledgments

The authors wish to acknowledge Dr. Thomas Kemper, whose discussions about these topics were instrumental in thinking about the impact of prenatal stimuli on brain development in the context of behavioral adaptation. This work was partially funded by R21 MH08792101 to JAM.

Disclosure statement

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

Author contributions

All authors contributed to the writing and edits of the manuscript.

Data availability

No novel data is presented in this manuscript.

Additional information

Funding

This work was supported by National Institutes of Health (US): [Grant Number MH08792101].

Notes on contributors

R. J. Rushmore

R. Jarrett Rushmore, Ph.D. is an Assistant Professor of Anatomy and Neurobiology at Boston University School of Medicine, and a research scientist at the Psychiatry Neuroimaging Laboratory at Brigham and Women's Hospital and the Center for Morphometric Analysis at Massachusetts General Hospital. He received his B.S. in neuroscience from Trinity College, and his Ph.D. in Anatomy and Neurobiology from Boston University. His research has focused on alterations of brain structure and function after pre- and perinatal insults, functional recovery and paradoxical effects after brain damage, non-invasive brain stimulation, and morphometric brain analysis.

J. A. McGaughy

Jill A. McGaughy, PhD is a Professor of Psychology at the University of New Hampshire. She received her BA in psychology from Bradley University and M.A./PhD in psychology from Ohio State University. Her research has focused on the neuromodulatory systems that underlie executive function, the development of these systems from adolescence to adulthood and the impact of early life insults on both the brain and cognition.

D. J. Mokler

David J. Mokler, PhD is Professor Emeritus of Biomedical Sciences at the University of New England College of Osteopathic Medicine. He received his BS in psychology and PhD in pharmacology/toxicology and neuroscience from Michigan State University. His research has focused on the organization of the serotonergic, dopaminergic and noradrenergic systems of the limbic system of the brain. He has worked on the functional neuroanatomy of the serotonergic system of the forebrain, the effects of drugs of abuse on the limbic system and the effects of exposure to prenatal protein malnutrition on the function of these systems in the adult rat brain.

D. L. Rosene

Douglas L. Rosene, PhD is Professor of Anatomy & Neurobiology at Boston University School of Medicine. He received his AB in Psychology from Stanford University and his PhD in Psychology and Neurobiology from the University of Rochester. His research investigates the neurobiological bases of learning, memory and executive system function in the brain. A major focus is on how these functions are affected by frank brain damage and by myelin changes that occur in normal aging. A related focus is on recovery of function after circumscribed damage in the monkey cortex and another is how prenatal protein malnutrition affects the brain and cognitive functions in the laboratory rat.