title: ZiBuPiYin recipe protects db/db mice from diabetes-associated cognitive decline through improving multiple pathological changes.
abstract: Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Liang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China; College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhan
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Zheng
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Anatomy department of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gong
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Rujiao
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Public Health department of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C531140:zibu piyin; D038362:Glycogen Synthase Kinase 3; D051528:Guanylate Kinases; D005947:Glucose