title: Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice.
abstract: Previous studies have suggested that minocycline can attenuate cognitive deficits in animal models of conditions such as Alzheimer's disease and cerebral ischemia through inhibiting microglia associated anti-inflammatory actions. However the pathway that minocycline targets to enhance cognitive performance is not fully defined. Here we examined the effects of minocycline on learning and memory in aged (22-month-old) C57 BL/6 mice. We treated one group of mice with minocycline (30 mg/kg/day), and another group of mice with donepezil (2 mg/kg/day) as a positive control. The Morris water maze and passive avoidance tests were used to evaluate the effects of minocycline on learning and memory deficits. We also used high-frequency stimulation-induced long-term potentiation and Golgi-Cox staining to assess the effect of minocycline on synaptic plasticity and synaptogenesis. The effects of minocycline on synapse-associated signaling proteins were determined by western blot. We found that minocycline ameliorates cognitive deficits, enhances neuroplasticity, activates brain-derived neurotrophic factor- extracellular signal-regulated kinases signaling and increases expression of Arc, EGR1 and PSD-95 in the CA1 and dentate gyrus regions of the hippocampus in aged mice. The effects of minocycline in aged mice were similar to those of donepezil. Our results suggest that minocycline could improve learning and memory through enhancing synaptic plasticity and synaptogenesis, modulating the expression of synapse-associated signaling proteins, which provide a rationale for exploring the viability of using minocycline treatment in cognitive deficits.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Cansheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Qiling
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China. Electronic address: xiaohongchenzssy@aliyun.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects; D000077265:Donepezil; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007189:Indans / Q000008:administration & dosage; D017774:Long-Term Potentiation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018697:Nootropic Agents / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage; D013569:Synapses / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D007189:Indans; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D010880:Piperidines; C092069:activity regulated cytoskeletal-associated protein; D000077265:Donepezil; D008911:Minocycline
keywords: Aging; Brain-derived neurotrophic factor; Cognitive deficit; Minocycline; Synaptic plasticity