Calbindin-1 Expression in the Hippocampus following Neonatal Hypoxia-Ischemia and Therapeutic Hypothermia and Deficits in Spatial Memory
PublisherS. Karger AG
MetadataShow full item record
AbstractHippocampal injury following neonatal hypoxia-ischemia (HI) leads to memory impairments despite therapeutic hypothermia (TH). In the hippocampus, the expression of calbindin-1 (Calb1), a Ca2+-buffering protein, increases during postnatal development and decreases with aging and neurodegenerative disorders. Since persistent Ca+ dysregulation after HI may lead to ongoing injury, persistent changes in hippocampal expression of Calb1 may contribute to memory impairments after neonatal HI. We hypothesized that, despite TH, neonatal HI persistently decreases Calb1 expression in the hippocampus, a change associated with memory deficits in the mouse. We induced cerebral HI in C57BL6 mice at postnatal day 10 (P10) with right carotid ligation and 45 min of hypoxia (FiO = 0.08), followed by normothermia (36°C, NT) or TH (31°C) for 4 h with anesthesia-shams as controls. Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) were used to grade brain injury and astrogliosis at P11, P18, and P40 prior to the assessment of Calb1 expression by IHC. The subset of mice followed to P40 also performed a memory behavior task (Y-maze) at P22-P26. Nonparametric statistics stratified by sex were applied. In both anterior and posterior coronal brain sections, hippocampal Calb1 expression doubled between P11 and P40 due to an increase in the cornus ammonis (CA) field (Kruskal-Wallis [KW] p < 0.001) and not the dentate gyrus (DG). Neonatal HI produced delayed (P18) and late (P40) deficits in the expression of Calb1 exclusively in the CA field (KW p = 0.02) in posterior brain sections. TH did not attenuate Calb1 deficits after HI. Thirty days after HI injury (at P40), GFAP scores in the hippocampus (p < 0.001, r =-0.47) and CA field (p < 0.001, r =-0.39) of posterior brain sections inversely correlated with their respective Calb1 expression. Both sexes demonstrated deficits in Y-maze testing, including approximately 40% lower spontaneous alterations performance and twice as much total impairment compared to sham mice (KW p < 0.001), but it was only in females that these deficits correlated with the Calb1 expression in the hippocampal CA field (p < 0.05) of the posterior sections. Hippocampal atrophy after neonatal HI also correlated with worse deficits in Y-maze testing, but it did not predict Calb1 deficits. Neonatal HI produces a long-lasting Calb1 deficit in the hippocampal CA field during development, which is not mitigated by TH. Late Calb1 deficit after HI may be the result of persistent astrogliosis and can lead to memory impairment, particularly in female mice. Copyright 2019 S. Karger AG, Basel. Copyright: All rights reserved.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85063530219&doi=10.1159%2f000497056&partnerID=40&md5=4b8913dfd458a3640d454dce1a4c90da; http://hdl.handle.net/10713/10564
- Delayed injury of hippocampal interneurons after neonatal hypoxia-ischemia and therapeutic hypothermia in a murine model.
- Authors: Chavez-Valdez R, Emerson P, Goffigan-Holmes J, Kirkwood A, Martin LJ, Northington FJ
- Issue date: 2018 Aug
- Therapeutic Hypothermia Provides Variable Protection against Behavioral Deficits after Neonatal Hypoxia-Ischemia: A Potential Role for Brain-Derived Neurotrophic Factor.
- Authors: Diaz J, Abiola S, Kim N, Avaritt O, Flock D, Yu J, Northington FJ, Chavez-Valdez R
- Issue date: 2017
- Hippocampal calbindin-1 immunoreactivity correlate of recognition memory performance in aged mice.
- Authors: Soontornniyomkij V, Risbrough VB, Young JW, Soontornniyomkij B, Jeste DV, Achim CL
- Issue date: 2012 May 10
- Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory.
- Authors: Takada SH, Dos Santos Haemmerle CA, Motta-Teixeira LC, Machado-Nils AV, Lee VY, Takase LF, Cruz-Rizzolo RJ, Kihara AH, Xavier GF, Watanabe IS, Nogueira MI
- Issue date: 2015 Jan 22
- Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia.
- Authors: Ness JM, Harvey CR, Washington JD, Roth KA, Carroll SL, Zhang J
- Issue date: 2008 Apr