title: Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation.
abstract: Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca(2+)-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca(2+)-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca(2+)-stimulated cAMP can affect the molecular outcome of physical exercise.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, 650500, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Genetics Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Ferzin
authors.initials: F
authors.lastname: Sethna
authors.affiliation: Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA Department of Psychology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA wangho@msu.edu.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D012420:Running
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1