Cerebral hemorrhage, a devastating subtype of stroke, is often caused by hypertension and cerebral amyloid angiopathy (CAA). Pathological evidence of CAA is detected in approximately half of all individuals over the age of 70 and is associated with cortical microinfarcts and cognitive impairment. The underlying pathophysiology of CAA is characterized by accumulation of pathogenic amyloid β (Aβ) fragments of amyloid precursor protein in the cerebral vasculature. Vascular deposition of Aβ damages the vessel wall, results in blood-brain barrier (BBB) leakiness, vessel occlusion or rupture, and leads to hemorrhages and decreased cerebral blood flow that negatively affects vessel integrity and cognitive function. Currently, the main hypothesis surrounding the mechanism of CAA pathogenesis is that there is an impaired clearance of Aβ peptides, which includes compromised perivascular drainage as well as dysfunction of BBB transport. Also, the immune response in CAA pathogenesis plays an important role. Therefore, the mechanism by which Aβ vascular deposition occurs is crucial for our understanding of CAA pathogenesis and for the development of potential therapeutic options.

Cerebral amyloid angiopathy (CAA) is one of the common causes of lobar intracerebral hemorrhage and vascular cognitive impairment (VCI) in the aging population. Increased amyloid plaque deposition within cerebral blood vessels, specifically the smooth muscle layer, is linked to increased cerebral microbleeds (CMBs) and impaired cognition in CAA. Studies in Alzheimer’s disease (AD) have shown that amyloid plaque pathology is more prevalent in the brains of elderly women (2/3rd of the dementia population) compared with men, however, there is a paucity of studies on sex differences in CAA . The objective of this study was to discern the sexual dichotomies in CAA . We utilized male and female Tg-SwDI mice (mouse model of CAA) at 12–14 months of age for this study. We evaluated sex differences in CMBs, cognitive function and inflammation. Cognition was assessed using Y-maze (spatial working memory) and Fear Conditioning (contextual memory). CMBs were quantified by ex vivo brain MRI scans. Inflammatory cytokines in brain were quantified using ELISA. Our results demonstrated that aging Tg-SwDI female mice had a significantly higher burden of CMBs on MRI as compared to males. Interestingly, these aging Tg-SwDI female mice also had significantly impaired spatial and contextual memory on Y maze and Fear Conditioning respectively. Furthermore, female mice had significantly lower circulating inflammatory cytokines, IL-1α, IL-2, IL-9, and IFN-γ, as compared to males. Our results demonstrate that aging female Tg-SwDI mice are more cognitively impaired and have higher number of CMBs, as compared to males at 12–14 months of age. This may be secondary to reduced levels of neural repair cytokines (IL-1α, IL-2, IL-9 and IFN-γ) involved in sex specific inflammatory signaling in CAA.

Potassium (K+) is the most abundant cation that plays a crucial role in various cellular processes in plants. Plants have developed an efficient mechanism for the acquisition of K+ when grown in K+ deficient or saline soils. A total of 47 K+ transport gene homologs (27 HAKs, 4 HKTs, 2 KEAs, 9 AKTs, 2 KATs, 2 TPCs, and 1 VDPC) have been identified in Sorghum bicolor. Of 47 homologs, 33 were identified as K+ transporters and the remaining 14 as K+ channels. Chromosome 2 has been found as the hotspot of K+ transporters with 9 genes. Phylogenetic analysis revealed the conservation of sorghum K+ transport genes akin to Oryza sativa. Analysis of regulatory elements indicates the key roles that K+ transport genes play under different biotic and abiotic stress conditions. Digital expression data of different developmental stages disclosed that expressions were higher in milk, flowering, and tillering stages. Expression levels of the genes SbHAK27 and SbKEA2 were higher during milk, SbHAK17, SbHAK11, SbHAK18, and SbHAK7 during flowering, SbHAK18, SbHAK10, and 23 other gene expressions were elevated during tillering inferring the important role that K+ transport genes play during plant growth and development. Differential transcript expression was observed in different tissues like root, stem, and leaf under abiotic stresses such as salt, drought, heat, and cold stresses. Collectively, the in-depth genome-wide analysis and differential transcript profiling of K+ transport genes elucidate their role in ion homeostasis and stress tolerance mechanisms.