Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

Rong Yin; Lin Yuan; Lili Ping; Liyuan Hu

doi:10.1016/j.resp.2015.09.011

Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

Respir Physiol Neurobiol. 2016 Jan:220:81-7. doi: 10.1016/j.resp.2015.09.011. Epub 2015 Sep 30.

Authors

Rong Yin¹, Lin Yuan², Lili Ping², Liyuan Hu²

Affiliations

¹ Neonatal Department, Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China. Electronic address: [email protected].
² Neonatal Department, Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China.

PMID: 26431790
DOI: 10.1016/j.resp.2015.09.011

Abstract

Neonatal bronchopulmonary dysplasia (BPD) might lead to an increased risk for brain injury. The present study aims to investigate the effects of neonatal BPD on neuronal apoptosis in the hippocampus and cognitive function and to explore the underlying mechanisms. The results revealed that BPD model rat pups exhibited more apoptotic cells in the hippocampus and longer escape latencies in the Morris maze test. Both the caspase-dependent and caspase-nondependent signal pathways were activated. Further examinations showed an elevated p53 level by BPD via HIF-1α induction, while the caspase-3 in the hippocampus was suppressed by both HIF-1α and p53 inhibitor. These findings suggested that neonatal BPD caused impaired cognitive function and neuron apoptosis in hippocampus via p53 and HIF-1α. Although the precise mechanism requires further investigation, this study provided new evidence for and an explanation of the impaired CNS developmental outcomes of BPD.

Keywords: Apoptosis; Bronchopulmonary dysplasia; HIF-1α; Hippocampus; Neuron; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / physiology*
Bronchopulmonary Dysplasia / pathology
Bronchopulmonary Dysplasia / physiopathology*
Caspase 3 / metabolism
Caspase 8 / metabolism
Caspase 9 / metabolism
Collagen / metabolism
Cytochromes c / metabolism
Disease Models, Animal
Hippocampus / pathology
Hippocampus / physiopathology*
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Lung / pathology
Lung / physiopathology
Maze Learning / physiology
Mitochondria / metabolism
Mitochondria / pathology
Neurons / pathology
Neurons / physiology*
Rats, Sprague-Dawley
Tumor Suppressor Protein p53 / antagonists & inhibitors
Tumor Suppressor Protein p53 / metabolism*
bcl-2-Associated X Protein / metabolism
fas Receptor / metabolism

Substances

Bax protein, rat
Fas protein, rat
Hif1a protein, rat
Hypoxia-Inducible Factor 1, alpha Subunit
Tumor Suppressor Protein p53
bcl-2-Associated X Protein
fas Receptor
Collagen
Cytochromes c
Casp3 protein, rat
Casp8 protein, rat
Casp9 protein, rat
Caspase 3
Caspase 8
Caspase 9