Abstract Age‐related changes in large‐vessel biomechanics may contribute to neurovascular dysfunction and region‐specific biochemical remodeling in the brain, with important implications for female health. This study investigated the impact of aging on neck vasculature and brain lipid biochemistry in female C57BL/6NHsd mice by comparing young (12 weeks; n = 10) and middle‐aged (52 weeks; n = 10) cohorts using ultrasound imaging, histology, and mass spectrometry. In vivo ultrasound quantified carotid and jugular hemodynamics, including wall shear stress (WSS), circumferential cyclic strain (CCS), pulsatility index, and volumetric flow. Ex vivo assessments included spatial lipid mapping in vessels and brain, and histology staining to quantify elastin‐to‐collagen ratios. Middle‐aged females exhibited reduced carotid systolic velocity, systolic WSS, and body weight–normalized carotid volumetric flow compared to young controls, while pulsatility index and CCS showed non‐significant decreases. Histology revealed a reduction in the carotid elastin‐to‐collagen ratio, consistent with vascular remodeling. Lipidomic profiling identified age‐dependent shifts in lipid headgroups, including decreases across multiple brain lipid classes, increased N‐acylethanolamides, alongside increases in carotid cardiolipin and lysophosphatidylethanolamine. Hippocampal spectra showed clearer age‐related separation than whole‐brain analyses. Correlation analyses identified moderate to strong associations between vascular biomechanics and lipid features across tissues, supporting coordinated neurovascular and biochemical aging in female mice.
Allison R. Jones, A. Jarrahi, Kylee Karpowich et al.· Physiological Reports· 0 citations
Perineuronal nets (PNNs) are widely reported to close developmental critical periods and restrict experience-dependent plasticity. Here we tested this model by selectively eliminating gene expression for aggrecan (Acan), an essential component of PNNs. In visual cortex, PNNs predominantly ensheath parvalbumin-positive (PV+) interneurons. Deletion of Acan in inhibitory neurons eliminated PNNs but did not prevent closure of the critical period. By comparison, deletion of Acan in all neurons, or only in excitatory forebrain neurons, sustained critical-period plasticity in adult mice. Visual plasticity in adults was associated with reduced cortical excitatory synaptic inputs onto layer 2/3 PV+ interneurons and increased expression of some immediate early genes in visual cortex but normal response strength and tuning properties of layer 2/3 excitatory neurons. These findings rectify long-standing models that misattribute closure of the critical period to PNNs and identify that aggrecan expressed by excitatory neurons resident in the surrounding neuropil limits visual plasticity.
Emily C. Crouse, Thomas C. Brown, Xiaokuang Ma et al.· bioRxiv· 0 citations