title: Patterns of cell death in the perinatal mouse forebrain.
abstract: The importance of cell death in brain development has long been appreciated, but many basic questions remain, such as what initiates or terminates the cell death period. One obstacle has been the lack of quantitative data defining exactly when cell death occurs. We recently created a "cell death atlas," using the detection of activated caspase-3 (AC3) to quantify apoptosis in the postnatal mouse ventral forebrain and hypothalamus, and found that the highest rates of cell death were seen at the earliest postnatal ages in most regions. Here we have extended these analyses to prenatal ages and additional brain regions. We quantified cell death in 16 forebrain regions across nine perinatal ages from embryonic day (E) 17 to postnatal day (P) 11 and found that cell death peaks just after birth in most regions. We found greater cell death in several regions in offspring delivered vaginally on the day of parturition compared with those of the same postconception age but still in utero at the time of collection. We also found massive cell death in the oriens layer of the hippocampus on P1 and in regions surrounding the anterior crossing of the corpus callosum on E18 as well as the persistence of large numbers of cells in those regions in adult mice lacking the pro-death Bax gene. Together these findings suggest that birth may be an important trigger of neuronal cell death and identify transient cell groups that may undergo wholesale elimination perinatally. J. Comp. Neurol. 525:47-64, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302.
authors.forename: Morgan
authors.initials: M
authors.lastname: Mosley
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302.
authors.forename: Charisma
authors.initials: C
authors.lastname: Shah
authors.affiliation: Department of Psychology, Center for Behavioral Neuroscience, Quinnipiac University, Hamden, Connecticut, 06518.
authors.forename: Kiriana A
authors.initials: KA
authors.lastname: Morse
authors.affiliation: Department of Psychology, Center for Behavioral Neuroscience, Quinnipiac University, Hamden, Connecticut, 06518.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Miloro
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, L5L 1C6, Canada.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Holmes
authors.affiliation: Department of Psychology, Center for Behavioral Neuroscience, Quinnipiac University, Hamden, Connecticut, 06518.
authors.forename: Todd H
authors.initials: TH
authors.lastname: Ahern
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Forger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010784:Photomicrography; D016548:Prosencephalon / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D051028:bcl-2-Associated X Protein
keywords: RRID:AB_2109645; RRID:AB_2298772; RRID:AB_231409; RRID:AB_2314667; activated caspase-3; bed nucleus of the stria terminalis; brain development; cell death; cingulate; hippocampus; hypothalamus; nucleus accumbens; oriens