title: Desipramine improves depression-like behavior and working memory by up-regulating p-CREB in Alzheimer's disease associated mice.
abstract: Aggregation of amyloid [Formula: see text] protein (A[Formula: see text] and progressive loss of memory are the main characteristics of Alzheimer's disease (AD). It is noteworthy that approximately 40% of AD patients have depressive symptom. The close correlation between cognitive deficits and mental depression suggests a possibility that antidepression treatment might be beneficial to cognitive improvement in AD. The present study, by using tail-suspension test (TST), forced swimming, alternative electro-stimulus Y maze test and immunohistochemistry, examined the neuroprotective effects of desipramine, a newer generation tricyclic antidepressants (TCA), and investigated its possible molecular mechanism. The results showed that: (1) intra-hippocampal injection of A[Formula: see text] induced depression-like behavior and associative learning deficits in mice, with an increased mean immobility time in tail-suspension and forced swimming test and an increased mean error times in Y maze test; (2) after treatment with desipramine (10[Formula: see text]mg/kg, i.p.), the average immobility time significantly decreased, from [Formula: see text][Formula: see text]s in A[Formula: see text] group to [Formula: see text][Formula: see text]s in A[Formula: see text] plus desipramine group ([Formula: see text]) in TST and from [Formula: see text][Formula: see text]s to [Formula: see text][Formula: see text]s ([Formula: see text] or 9, [Formula: see text]) in forced swimming test, respectively;the mean error times of mice in Y maze test also significantly decreased, from [Formula: see text] in A[Formula: see text] group to [Formula: see text] in A[Formula: see text] plus desipramine group ([Formula: see text], [Formula: see text]); (3) desipramine administration significantly prevented against A[Formula: see text]-induced down-regulation of phosphorylated cAMP response element binding protein (p-CREB) in the hippocampus. These results indicate that A[Formula: see text] could concurrently mimic the depression-like behavior and working memory disorder in mice, while desipramine could effectively reverse both the deficits induced by A[Formula: see text]. The neuroprotection of desipramine may be involved in the up-regulation of p-CREB level in the hippocampus of mice.
authors.affiliation: * The First Affiliated Hospital, Shanxi Medical University, Taiyuan, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: * The First Affiliated Hospital, Shanxi Medical University, Taiyuan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: * The First Affiliated Hospital, Shanxi Medical University, Taiyuan, China.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Yu
authors.affiliation: † Department of Physiology, Shanxi Medical University, Taiyuan, China.
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.affiliation: † Department of Physiology, Shanxi Medical University, Taiyuan, China.|‡ School of PE, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Sun
authors.affiliation: † Department of Physiology, Shanxi Medical University, Taiyuan, China.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003891:Desipramine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000929:Antidepressive Agents, Tricyclic; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003891:Desipramine
keywords: Amyloid protein; Desipramine; depression; p-CREB; working memory