Neuritin can normalize neural deficits of Alzheimer's disease.
Reductions in hippocampal neurite complexity and synaptic plasticity are believed to contribute to the progressive impairment in episodic memory and the mild cognitive decline that occur particularly in the early stages of Alzheimer's disease (AD). Despite the functional and therapeutic importance for patients with AD, intervention to rescue or normalize dendritic elaboration and synaptic plasticity is scarcely provided. Here we show that overexpression of neuritin, an activity-dependent protein, promoted neurite outgrowth and maturation of synapses in parallel with enhanced basal synaptic transmission in cultured hippocampal neurons. Importantly, exogenous application of recombinant neuritin fully restored dendritic complexity as well as spine density in hippocampal neurons prepared from Tg2576 mice, whereas it did not affect neurite branching of neurons from their wild-type littermates. We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
K
K
An
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
J H
JH
Jung
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
A Y
AY
Jeong
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
H G
HG
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
S Y
SY
Jung
Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Korea.
K
K
Lee
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
H J
000000019108151X
HJ
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
S-J
SJ
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
T-Y
TY
Jeong
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
Y
Y
Son
Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Korea.
H-S
HS
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea.
J-H
JH
Kim
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008867:Microtomy; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D046509:Tissue Culture Techniques
D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C484377:Nrn1 protein, mouse; D011994:Recombinant Proteins