title: Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex.
abstract: Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.
authors.affiliation: Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address: acamaral@bu.edu.
authors.forename: A C
authors.initials: AC
authors.lastname: Amaral
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jakovcevski
authors.affiliation: Department of Psychology, University of New Hampshire, Durham, NH 03824, United States.
authors.forename: J A
authors.initials: JA
authors.lastname: McGaughy
authors.affiliation: Department of Radiation Oncology, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: S K
authors.initials: SK
authors.lastname: Calderwood
authors.affiliation: Department of Biomedical Sciences, University of New England, Biddeford, ME 02120, United States.
authors.forename: D J
authors.initials: DJ
authors.lastname: Mokler
authors.affiliation: Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: R J
authors.initials: RJ
authors.lastname: Rushmore
authors.affiliation: Judge Baker Children's Center and Department of Psychiatry, Harvard Medical School, Boston, MA 02120, United States.
authors.forename: J R
authors.initials: JR
authors.lastname: Galler
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: S A
authors.initials: SA
authors.lastname: Akbarian
authors.affiliation: Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: D L
authors.initials: DL
authors.lastname: Rosene
mesh_terms: D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D044342:Malnutrition / Q000235:genetics* / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497068:Kcnj3 protein, rat; D003847:Deoxyglucose
keywords: 2-deoxyglucose; GIRK1; KCNJ3; brain activity; prefrontal cortex; prenatal protein malnutrition