title: Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure.
abstract: Cognitive impairment is a common finding in patients with chronic obstructive pulmonary disease (COPD), but little attention has been focused on therapeutic intervention for this complication. Chronic intermittent hypoxia hypercapnia (CIHH) exposure is considered to be responsible for the pathogenesis of COPD. Dl-3n-Butylphthalide (NBP), extracted from Apium graveolens Linn, has displayed a broad spectrum of neuroprotective properties. Our study aimed to investigate the potential of NBP on CIHH-induced cognitive deficits. The cognitive function of rats after CIHH exposure was evaluated by the Morris water maze, which showed that the NBP treated group performed better in the navigation test. NBP activated BDNF and phosphorylated CREB, the both are responsible for neuroprotection. Additionally, NBP decreased CIHH induced apoptosis. Moreover, NBP further induced the expression of HIF-1α, accompanied by the up-regulation of the autophagy proteins Bnip3, Beclin-1 and LC3-II. Finally, NBP also reversed the decreased expression of SIRT1 and PGC-1α, but the expression of Tfam, Cox II and mtDNA remained unchanged. These results suggested that the neuroprotective effects of NBP under CIHH condition possibly occurred through the inhibition of apoptosis, promotion of hypoxia-induced autophagy, and activation of the SIRT1/PGC-1α signalling pathway, while stimulation of mitochondrial biogenesis may not be a characteristic response.
authors.affiliation: 1] The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China [2] The First People's Hospital of Huzhou, Huzhou 313000, China [3].
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Min
authors.affiliation: 1] The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China [2].
authors.forename: Xin-long
authors.initials: XL
authors.lastname: Huo
authors.affiliation: The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Xiang
authors.affiliation: The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Qin
authors.affiliation: The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Ke-qin
authors.initials: KQ
authors.lastname: Chai
authors.affiliation: Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: The Center of Neurology and Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xiao-tong
authors.initials: XT
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006935:Hypercapnia / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D063269:Mitochondrial Turnover; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001572:Benzofurans; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; C027125:3-n-butylphthalide; C488368:Sirt1 protein, rat; D056564:Sirtuin 1