Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice DOI Creative Commons

Letizia Dacomo,

Pietro La Vitola, Laura Brunelli

и другие.

Aging Cell, Год журнала: 2024, Номер 23(10)

Опубликована: Июль 3, 2024

Abstract Frailty is a geriatric, multi‐dimensional syndrome that reflects multisystem physiological change and transversal measure of reduced resilience to negative events. It characterized by weakness, frequent falls, cognitive decline, increased hospitalization dead represents risk factor for the development Alzheimer's disease (AD). The fact frailty recognized as reversible condition encourages identification earlier biomarkers timely predict prevent its occurrence. SAMP8 (Senescence‐Accelerated Mouse Prone‐8) mice represent most appropriate preclinical model this aim were used in study carry transcriptional metabolic analyses brain plasma, respectively, upon characterization at cognitive, motor, structural, neuropathological level 2.5, 6, 9 months age. At 2.5 months, started displaying memory deficits, muscle motor impairment. Functional alterations associated with neurodevelopmental deficiency neuronal density glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing 6 whereas plasma metabolomics allowed segregate from SAMR1 already age detecting constitutively lower levels acylcarnitines lipids all ages investigated correlating functional deficits signs. Our findings suggest central level, metabolomic changes might allow early assess frail leading dementia development, which paves foundation future investigation clinical setting.

Язык: Английский

Senescence Accelerated Mouse-Prone 8: a Model of Neuroinflammation and Aging with Features of Sporadic Alzheimer’s disease DOI Creative Commons
Jun Yi Ong, Kazunori Sasaki, Farhana Ferdousi

и другие.

Stem Cells, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract The large majority of Alzheimer’s disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage AD familial, known Paradoxically, there few validated mouse models but many familial AD. Senescence Accelerated Mouse-Prone 8 (SAMP8) mice model accelerated aging features They exhibit more complete suite human AD-relevant pathologies than most models. SAMP8 brains characterized by inflammation, glial activation, β-amyloid deposits, and hyperphosphorylated Tau. excess amyloid deposits congregate around blood vessels leading to vascular impairment leaky BBBs in these mice. also neuronal cell death, feature not typically seen Additionally, adult hippocampal neurogenesis is decreased correspondingly, they have reduced cognitive ability. line this, LTP significantly compromised No perfect limited the lack clarity about their genomic differences from control SAMR1 (Senescence Mouse-Resistant 1) although transcriptomics changes being revealed. To further complicate matters, multiple substrains emerged over years, sometimes making comparisons studies difficult. Despite challenges, we argue that can be useful for studying symptoms propose important experiments strengthen this already model.

Язык: Английский

Процитировано

0
Investigating gut alterations in Alzheimer’s disease: In-depth analysis with micro- and nano-3D X-ray phase contrast tomography DOI Creative Commons
Francesca Palermo,

N. Marrocco,

Letizia Dacomo

и другие.

Science Advances, Год журнала: 2025, Номер 11(5)

Опубликована: Янв. 31, 2025

Alzheimer’s disease (AD), a debilitating neurodegenerative disorder, remains one of the foremost public health challenges affecting more than 30 million people worldwide with etiology still largely enigmatic. The intricate gut-brain axis, serving as vital communication network between gut and brain, appears to wield influence in progression AD. Our study showcases remarkable precision x-ray phase-contrast tomography (XPCT) conducting an advanced three-dimensional examination cellular composition structure. exploitation micro- nano-XPCT on various AD mouse models unveiled relevant alterations villi crypts, transformations Paneth goblet cells, along detection telocytes, neurons, erythrocytes, mucus secretion by cells within cavity. observed structural variations may elucidate transition from dysbiosis neurodegeneration cognitive decline. Leveraging XPCT could prove pivotal early prognosis disease.

Язык: Английский

Процитировано

0
Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice DOI Creative Commons

Letizia Dacomo,

Pietro La Vitola, Laura Brunelli

и другие.

Aging Cell, Год журнала: 2024, Номер 23(10)

Опубликована: Июль 3, 2024

Abstract Frailty is a geriatric, multi‐dimensional syndrome that reflects multisystem physiological change and transversal measure of reduced resilience to negative events. It characterized by weakness, frequent falls, cognitive decline, increased hospitalization dead represents risk factor for the development Alzheimer's disease (AD). The fact frailty recognized as reversible condition encourages identification earlier biomarkers timely predict prevent its occurrence. SAMP8 (Senescence‐Accelerated Mouse Prone‐8) mice represent most appropriate preclinical model this aim were used in study carry transcriptional metabolic analyses brain plasma, respectively, upon characterization at cognitive, motor, structural, neuropathological level 2.5, 6, 9 months age. At 2.5 months, started displaying memory deficits, muscle motor impairment. Functional alterations associated with neurodevelopmental deficiency neuronal density glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing 6 whereas plasma metabolomics allowed segregate from SAMR1 already age detecting constitutively lower levels acylcarnitines lipids all ages investigated correlating functional deficits signs. Our findings suggest central level, metabolomic changes might allow early assess frail leading dementia development, which paves foundation future investigation clinical setting.

Язык: Английский

Процитировано

3