title: Effects of birth asphyxia on neonatal hippocampal structure and function in the spiny mouse.
abstract: Studies of human neonates, and in animal experiments, suggest that birth asphyxia results in functional compromise of the hippocampus, even when structural damage is not observable or resolves in early postnatal life. The aim of this study was to determine if changes in hippocampal function occur in a model of birth asphyxia in the precocial spiny mouse where it is reported there is no major lesion or infarct. Further, to assess if, as in human infants, this functional deficit has a sex-dependent component. At 37 days gestation (term=39 days) spiny mice fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5min of in utero asphyxia causing systemic acidosis and hypoxia. At 5 days of age hippocampal function was assessed ex vivo in brain slices, or brains were collected for examination of structure or protein expression. This model of birth asphyxia did not cause infarct or cystic lesion in the postnatal day 5 (P5) hippocampus, and the number of proliferating or pyknotic cells in the hippocampus was unchanged, although neuronal density in the CA1 and CA3 was increased. Protein expression of synaptophysin, brain-derived neurotrophic factor (BDNF), and the inositol trisphosphate receptor 1 (IP(3)R1) were all significantly increased after birth asphyxia, while long-term potentiation (LTP), paired pulse facilitation (PPF), and post-tetanic potentiation (PTP) were all reduced at P5 by birth asphyxia. In control P5 pups, PPF and synaptic fatigue were greater in female compared to male pups, and after birth asphyxia PPF and synaptic fatigue were reduced to a greater extent in female vs. male pups. In contrast, the asphyxia-induced increase in synaptophysin expression and neuronal density were greater in male pups. Thus, birth asphyxia in this precocial species causes functional deficits without major structural damage, and there is a sex-dependent effect on the hippocampus. This may be a clinically relevant model for assessing treatments delivered either before or after birth to protect this vulnerable region of the developing brain.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia. bobbi.fleiss@neuro.gu.se
authors.forename: B
authors.initials: B
authors.lastname: Fleiss
authors.forename: H A
authors.initials: HA
authors.lastname: Coleman
authors.forename: M
authors.initials: M
authors.lastname: Castillo-Melendez
authors.forename: Z
authors.initials: Z
authors.lastname: Ireland
authors.forename: D W
authors.initials: DW
authors.lastname: Walker
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001237:Asphyxia / Q000473:pathology* / Q000503:physiopathology*; D001238:Asphyxia Neonatorum / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology* / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051189:Murinae; D011247:Pregnancy; D012727:Sex Characteristics; D055366:Synaptic Potentials; D013572:Synaptic Vesicles / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016708:Synaptophysin; D002118:Calcium