title: Overexpression of Heme Oxygenase 1 Impairs Cognitive Ability and Changes the Plasticity of the Synapse.
abstract: The expression of heme oxygenase 1 (HO-1) in the cortex and hippocampus is higher in Alzheimer's disease (AD) and mild cognitive impairment patients than healthy individuals, and epidemiological studies suggest that HO-1 is an important factor for AD. However, its influence on nerve function is poorly understood. Here, we studied the effect of the overexpression of HO-1 on the cognitive and synaptic plasticity in 3-month-old mice. We found that the overexpression of HO-1 induced spatial learning and memory deficits with an apparent decrease of AMPKR, NMDAR, postsynaptic density protein 95, synapsin I, synaptophysin, and microtubule-associated protein 2, all of which are memory-related synaptic proteins. Concurrently, HO-1 could co-express and induce the aggregation of Aβ42 and Aβ oligomer in the hippocampus area. Additionally, our research is the first to demonstrate that HO-1 changes the morphology of the synapse to impair the neural circuit. These results indicate that the overexpression of HO-1 can damage synaptic plasticity in early stages to induce AD-like pathology and cognitive abnormality in mice.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: People's Hospital of Yuxi City, Yuki, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Si
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Yanze
authors.initials: Y
authors.lastname: Li
authors.affiliation: GE Healthcare Life Sciences, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D045744:Cell Line, Tumor; D003071:Cognition / Q000502:physiology*; D003712:Dendrites / Q000201:enzymology / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D007859:Learning Disabilities / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000201:enzymology* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D017470:Receptors, Glutamate; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Alzheimer’s disease; amyloid-β oligomer; dendritic spine; heme oxygenase 1; synaptic plasticity