Brain Serotonin System Controls Maternal Behavior

Main Category: Neurology / Neuroscience
Article Date: 19 Aug 2008 - 2:00 PDT

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New research from Case Western Reserve University School of Medicine demonstrates the importance of brain serotonin for offspring survival.

The study, "Serotonergic Transcriptional Programming Determines Maternal Behavior and Offspring Survival," appears in the September 2008 issue of Nature Neuroscience. It uses Pet-1 mutant mice, genetically altered mice carrying a mutation in a gene that directs the development of the brain serotonin neurotransmitter system, to investigate the system's role in maternal behavior and its impact on offspring survival.

"Alterations in brain serotonin levels have been linked to several mental health disorders such as depression and anxiety," said Evan Deneris, Ph.D., senior author on the study and Professor of Neurosciences at Case Western Reserve University School of Medicine who, together with Jessica Lerch-Haner, Ph.D.-student in the School of Medicine, lead this study. "However, despite the prevalence of postpartum depression and the frequent use of serotonergic drugs such as Prozac and Zoloft to treat this disorder, a requirement for maternal serotonin function in the mother's behavior toward her offspring had not been convincingly demonstrated, until now."

Although Pet-1 deficient mice mothers showed normal rates of pregnancy and gave birth to normal numbers of offspring, none of their offspring survived to five days of age, therefore directly demonstrating a critical role for the brain serotonin neurotransmitter system in reproductive success of mice.

Further studies indicated that a specific deficiency of maternal care was the cause of pup mortality. Rodent neonates are not able to maintain proper body temperature on their own; essential maternal care includes construction of proper nests and huddling of offspring in the nests for warmth. Although Pet-1 deficient mothers nursed their offspring they often failed to build suitable nests and never organized offspring in a huddle. Thus, offspring neglect led to death from cold exposure.

The study also showed that a partial restoration of Pet-1 function in the developing brain of females partially restored their serotonin levels and maternal behavior in adulthood. This finding indicated that subtle changes in the embryonic formation of the brain serotonin system in females can impact the quality of the maternal care they later provide for their offspring.

Future studies with Pet-1 deficient mothers may help to further elucidate the link between serotonin and maternal behavior and lead to the development of new therapeutic approaches for treatment of post-partum depression and child neglect.

Lead author on the study is Jessica K. Lerch-Haner, who is a graduate student in Deneris's lab. Other authors are Dargan Frierson, University of North Carolina, Wilmington Dept. of Mathematics and Statistics; LaTasha Crawford and Sheryl Beck, Dept. of Anesthesiology, Children's Hospital of Philadelphia and Department of Neuroscience, University of Pennsylvania.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and 15th largest among the nation's medical schools for research funding from the National Institutes of Health. Eleven Nobel Laureates have been affiliated with the school.

The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching and in 2002, became the third medical school in history to receive a pre-eminent review from the national body responsible for accrediting the nation's academic medical institutions. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century.

Annually, the School of Medicine trains more than 600 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report Guide to Graduate Education. The School of Medicine's primary clinical affiliate is University Hospitals and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic Foundation, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.

Case Western Reserve University
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