title: Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats.
abstract: Memory loss and cognition decline are the main clinical manifestations of Alzheimer's disease (AD). Amyloid β protein (Aβ) aggregated in the brain is one of the key pathological characteristics of AD and responsible for the deficits in learning and memory. It is reported that davunetide, an octapeptide derived from activity-dependent neuroprotective protein (ADNP), inhibited Aβ aggregation and Aβ-induced neurotoxicity. To further characterize the neuroprotective roles of davunetide and its possible mechanism, the present study investigated the effects of davunetide on Aβ1-42-induced impairments in spatial memory, synaptic plasticity and hippocampal AKT level. In Morris water maze (MWM) test, bilateral intrahippocampal injection of Aβ1-42 significantly increased escape latency and decreased target quadrant swimming time of rats, while three weeks of intranasal application of davunetide reversed the Aβ1-42-induced learning deficits and memory loss in a dose-dependent manner. In vivo field potentiation recording showed that Aβ1-42 suppressed long-term potentiation (LTP) of excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 region of rats, while davunetide effectively blocked the suppression of LTP, without affecting paired-pulse facilitation (PPF). Western blotting experiments showed a significant decrease in the level of hippocampal p-AKT (Ser473), not total AKT, in Aβ1-42 only group, which was mostly antagonized by davunetide treatment. These findings demonstrate that davunetide, probably by enhancing PI3K/AKT pathway, plays an important positive role in attenuating Aβ1-42-induced impairments in spatial memory and synaptic plasticity, suggesting that davunetide could be an effective therapeutic candidate for the prevention and treatment of neurodegenerative disease such as AD.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Severe Liver Disease, The 3ird People's Hospital of Taiyuan, Taiyuan 030012, PR China.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wei
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Kong
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Sheng-Xiao
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: jinshunqi@sxmu.edu.cn.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D009842:Oligopeptides / Q000627:therapeutic use*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D009842:Oligopeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D051058:Oncogene Protein v-akt; C425904:davunetide
keywords: Amyloid β protein; Davunetide; Long term potentiation; Phosphorylated AKT; Spatial memory; Synaptic plasticity