Characterization of age- and stage-dependent impaired adult subventricular neurogenesis in 5XFAD mouse model of Alzheimer’s disease
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Alzheimer’s disease (AD) is a progressive neurodegenerative diseasecharacterized by cognitive decline. Several recent studiesdemonstrated that impaired adult neurogenesis could contributeto AD-related cognitive impairment. Adult subventricularzone (SVZ) neurogenesis, which occurs in the lateral ventricles,plays a crucial role in structural plasticity and neural circuitmaintenance. Alterations in adult SVZ neurogenesis are earlyevents in AD, and impaired adult neurogenesis is influencedby the accumulation of intracellular Aβ. Although Aβ-overexpressingtransgenic 5XFAD mice are an AD animal model wellrepresentative of Aβ-related pathologies in the brain, the characterizationof altered adult SVZ neurogenesis following ADprogression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesischanges with AD progression in 2-, 4-, 8-, and 11-montholdmale 5XFAD mice. We first investigated the Aβ accumulationin the SVZ using the 4G8 antibody. We observed intracellularAβ accumulation in the SVZ of 2-month-old 5XFADmice. In addition, 5XFAD mice exhibited significantly increasedAβ deposition in the SVZ with age. Next, we performed a histologicalanalysis to investigate changes in various phases of adultneurogenesis, such as quiescence, proliferation, and differentiation,in SVZ. Compared to age-matched wild-type (WT) mice,quiescent neural stem cells were reduced in 5XFAD mice from2-11 months of age. Moreover, proliferative neural stem cellswere decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in5XFAD mice from 2-11 months of age. Intriguingly, we foundthat adult SVZ neurogenesis was reduced with aging in healthymice. Taken together, our results revealed that impairment ofadult SVZ neurogenesis appears with aging or AD progression.
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative diseasecharacterized by cognitive decline. Several recent studiesdemonstrated that impaired adult neurogenesis could contributeto AD-related cognitive impairment. Adult subventricularzone (SVZ) neurogenesis, which occurs in the lateral ventricles,plays a crucial role in structural plasticity and neural circuitmaintenance. Alterations in adult SVZ neurogenesis are earlyevents in AD, and impaired adult neurogenesis is influencedby the accumulation of intracellular Aβ. Although Aβ-overexpressingtransgenic 5XFAD mice are an AD animal model wellrepresentative of Aβ-related pathologies in the brain, the characterizationof altered adult SVZ neurogenesis following ADprogression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesischanges with AD progression in 2-, 4-, 8-, and 11-montholdmale 5XFAD mice. We first investigated the Aβ accumulationin the SVZ using the 4G8 antibody. We observed intracellularAβ accumulation in the SVZ of 2-month-old 5XFADmice. In addition, 5XFAD mice exhibited significantly increasedAβ deposition in the SVZ with age. Next, we performed a histologicalanalysis to investigate changes in various phases of adultneurogenesis, such as quiescence, proliferation, and differentiation,in SVZ. Compared to age-matched wild-type (WT) mice,quiescent neural stem cells were reduced in 5XFAD mice from2-11 months of age. Moreover, proliferative neural stem cellswere decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in5XFAD mice from 2-11 months of age. Intriguingly, we foundthat adult SVZ neurogenesis was reduced with aging in healthymice. Taken together, our results revealed that impairment ofadult SVZ neurogenesis appears with aging or AD progression.
참고문헌 (37)
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