TY - JOUR
T1 - Shati/Nat8l Overexpression Improves Cognitive Decline by Upregulating Neuronal Trophic Factor in Alzheimer’s Disease Model Mice
AU - Chino, Kakeru
AU - Izuo, Naotaka
AU - Noike, Hiroshi
AU - Uno, Kyosuke
AU - Kuboyama, Tomoharu
AU - Tohda, Chihiro
AU - Muramatsu, Shin Ichi
AU - Nitta, Atsumi
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/9
Y1 - 2022/9
N2 - Alzheimer’s disease (AD) is a type of dementia characterized by the deposition of amyloid β, a causative protein of AD, in the brain. Shati/Nat8l, identified as a psychiatric disease related molecule, is a responsive enzyme of N-acetylaspartate (NAA) synthesis. In the hippocampi of AD patients and model mice, the NAA content and Shati/Nat8l expression were reported to be reduced. Having recently clarified the involvement of Shati/Nat8l in cognitive function, we examined the recovery effect of the hippocampal overexpression of Shati/Nat8l in AD model mice (5XFAD). Shati/Nat8l overexpression suppressed cognitive dysfunction without affecting the Aβ burden or number of NeuN-positive neurons. In addition, brain-derived neurotrophic factor mRNA was upregulated by Shati/Nat8l overexpression in 5XFAD mice. These results suggest that Shati/Nat8l overexpression prevents cognitive dysfunction in 5XFAD mice, indicating that Shati/Nat8l could be a therapeutic target for AD.
AB - Alzheimer’s disease (AD) is a type of dementia characterized by the deposition of amyloid β, a causative protein of AD, in the brain. Shati/Nat8l, identified as a psychiatric disease related molecule, is a responsive enzyme of N-acetylaspartate (NAA) synthesis. In the hippocampi of AD patients and model mice, the NAA content and Shati/Nat8l expression were reported to be reduced. Having recently clarified the involvement of Shati/Nat8l in cognitive function, we examined the recovery effect of the hippocampal overexpression of Shati/Nat8l in AD model mice (5XFAD). Shati/Nat8l overexpression suppressed cognitive dysfunction without affecting the Aβ burden or number of NeuN-positive neurons. In addition, brain-derived neurotrophic factor mRNA was upregulated by Shati/Nat8l overexpression in 5XFAD mice. These results suggest that Shati/Nat8l overexpression prevents cognitive dysfunction in 5XFAD mice, indicating that Shati/Nat8l could be a therapeutic target for AD.
KW - AAV vector
KW - Alzheimer’s disease
KW - Amyloid β
KW - BDNF
KW - Cognitive dysfunction
KW - Shati/Nat8l
UR - http://www.scopus.com/inward/record.url?scp=85132816269&partnerID=8YFLogxK
U2 - 10.1007/s11064-022-03649-2
DO - 10.1007/s11064-022-03649-2
M3 - 学術論文
C2 - 35759136
AN - SCOPUS:85132816269
SN - 0364-3190
VL - 47
SP - 2805
EP - 2814
JO - Neurochemical Research
JF - Neurochemical Research
IS - 9
ER -