Specificity and efficiency of tamoxifen-mediated Cre induction is equivalent regardless of age

iScience, Год журнала: 2023, Номер 26(12), С. 108413 - 108413

Опубликована: Ноя. 9, 2023

Temporally controlling Cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report early post-natal/juvenile (<2 m.o.) Tam induction, but age-related neurodegeneration and aging can require in older mice (>12 m.o.). While anecdotally reported as problematic, there are no published comparisons of Tam-mediated at late ages. Here, microglial-specific Cx3cr1creERT2 were crossed to a floxed NuTRAP reporter compare (3-6 (20 Specificity efficiency microglial labeling 21-22 m.o. identical induced with Age-related translatomic changes also similar regardless age. Each flox mouse line should be independently validated, however, these findings demonstrate that performed even into ages generalizable other inducible models.

Язык: Английский

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Autoimmune hypothesis of Alzheimer's disease: Unanswered question

Journal of Neurophysiology, Год журнала: 2024, Номер 132(3), С. 929 - 942

Опубликована: Авг. 20, 2024

Alzheimer’s disease (AD) was described more than a century ago. However, there are still no effective approaches to its treatment, which may suggest that the search for cure is not being conducted in most productive direction. AD begins as selective impairments of declarative memory with deficits other cognitive functions. Therefore, understanding pathogenesis has include this selectivity. Currently, main efforts aimed at prevention and treatment based on dominating hypothesis pathogenesis: amyloid hypothesis. But does explain since β-amyloid accumulates extracellularly should be toxic all types cerebral neurons, only “memory engram neurons.” To impairment, I propose autoimmune AD, analysis risk factors molecular mechanisms formation. Memory formation associated epigenetic modifications chromatin neurons and, therefore, might accompanied by expression memory-specific proteins recognized adaptive immune system “non-self” antigens. Normally, brain protected blood-brain barrier (BBB). All provoke BBB disruptions, possibly leading an reaction against neurons. This would make them selectively sensitive tauopathy. If confirmed, strategies radically changed.

Язык: Английский

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Myeloid antigen-presenting cells in neurodegenerative diseases: a focus on classical and non-classical MHC molecules

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Дек. 9, 2024

In recent years, increasing evidence has highlighted the critical role of myeloid cells, specifically those that present antigen (APCs) in health and disease. These shape progression development neurodegenerative disorders, where considerable interplay between immune system neurons influences course disease pathogenesis. Antigen-presenting cells display different classes major histocompatibility complex (MHC) MHC-like proteins on their surface for presenting various types antigens to a wide variety T cells. While most studies focus MHC class I II molecules disease, there is still much remains unknown about non-polymorphic such as CD1d MR1. Thus, this review, we will summarize findings regarding contributions both classical non-classical molecules, particularly microglial APCs, diseases. This offer better understanding altered mechanisms may pave way novel therapeutic strategies targeting cell-MHC interactions, mitigate neurodegeneration its associated pathology.

Язык: Английский

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Consistent specificity and efficiency of tamoxifen-mediated cre induction across ages

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 22, 2023

Summary Temporally controlling cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report Tam at early post-natal/juvenile (<2 m.o.) mouse ages, but age-related neurodegeneration and aging can require in older mice (>12 m.o.). While anecdotally reported as problematic, there are no published comparisons of mediated late ages. Here, microglial-specific Cx3cr1 creERT 2 were crossed to a floxed NuTRAP reporter compare (3-6 (20 Specificity efficiency microglial labeling 21-22 m.o. identical induced with 3-6 or 20 age. Age-related translatomic changes also similar regardless Each flox line should be validated independently, however, these findings demonstrate that Tam-mediated performed even into

Язык: Английский

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