Comparison of two bedding types on the breeding fecundity of C57BL/6J mice.

One of the favored options for generating complex transgenic laboratory mice is through in-house breeding and management strategies. One consideration in the management of these colonies is how the animals' environment may affect reproductive success. Several aspects of the microenvironment can be controlled or manipulated, including cage type, bedding, enrichment, diet, and temperature and humidity. This study sought to evaluate reproductive outcomes for C57BL/6J mice that were randomly assigned to one of two different bedding types: paper based or corncob bedding. Our hypothesis was there would be no significant difference in reproductive outcomes between the two bedding types. A total of 10 males and 10 females were paired at 45 days of age. Animals were allowed to breed for 15 consecutive weeks. Cages were checked daily for the presence of pups and a pup count was performed at 7 days of age. Weaning occurred at 20 or 21 days of age, at which time a final pup count, pup weight, and sex were recorded. All litters born and pups weaned in the 15-week timeframe were used for data analysis. Statistical analysis compared cannibalization between the two groups and the results showed no statistical difference between groups (p > 0.05). Other parameters analyzed included average litter size, average weaning weight, and number of litters per group. All pups counted at Day 7 survived to weaning age in both groups. We concluded that both bedding types produced similar success regarding breeding fecundity in C57BL/6J mice.

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice.

Introduction: Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1. Methods: We used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor (Igf1r) deficiency and evaluated the development of cerebrovascular pathologies and cognitive dysfunction. Results: VSMC-specific Igf1r deficiency led to impaired cerebral myogenic autoregulation, independent of blood pressure changes, which was also associated with impaired spatial learning and memory function as measured by radial arm water maze and impaired motor learning measured by rotarod. In contrast, VSMC-specific IGF-1 receptor knockdown did not lead to cerebral microvascular rarefaction. Discussion: These studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.

Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM).

Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 µm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research.