Rabbit Anti-Human PVALB (N-terminal) Polyclonal antibody

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by two core symptoms: impaired social interaction and communication, and restricted, repetitive behaviors and interests. The pathophysiology of ASD is not yet fully understood, due to a plethora of genetic and environmental risk factors that might be associated with or causal for ASD. Recent findings suggest that one putative convergent pathway for some forms of ASD might be the downregulation of the calcium-binding protein parvalbumin (PV). PV-deficient mice (PV-/-, PV+/-), as well as Shank1-/-, Shank3-/-, and VPA mice, which show behavioral deficits relevant to all human ASD core symptoms, are all characterized by lower PV expression levels. Methods: Based on the hypothesis that PV expression might be increased by 17-beta estradiol (E2), PV+/- mice were treated with E2 from postnatal days 5-15 and ASD-related behavior was tested between postnatal days 25 and 31. Results: PV expression levels were significantly increased after E2 treatment and, concomitantly, sociability deficits in PV+/- mice in the direct reciprocal social interaction and the 3-chamber social approach assay, as well as repetitive behaviors, were attenuated. E2 treatment of PV+/+ mice did not increase PV levels and had detrimental effects on sociability and repetitive behavior. In PV-/- mice, E2 obviously did not affect PV levels; tested behaviors were not different from the ones in vehicle-treated PV-/- mice. Conclusion: Our results suggest that the E2-linked amelioration of ASD-like behaviors is specifically occurring in PV+/- mice, indicating that PV upregulation is required for the E2-mediated rescue of ASD-relevant behavioral impairments.

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp-Pkd1(-/-)) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp-Pkd1(-/-) mice display reduced serum levels of magnesium (Mg2+), calcium (Ca2+), sodium (Na+), and phosphate (P-i) compared with control (Pkd1(+/+)) mice and renal Mg2+, Ca2+, and P-i wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of Ksp-Pkd1(-/-) mice compared with controls. Similarly, decreased renal gene expression of markers for TAL (Umod) and DCT (Pvalb) was observed in iKsp-Pkd1(-/-) mice. Conversely, mRNA expression levels in kidney of genes encoding solute and water transporters in the proximal tubule (Abcg2 and Slc34a1) and collecting duct (Aqp2, Scnn1a, and Scnn1b) remained comparable between control and iKsp-Pkd1(-/-) mice, although a water reabsorption defect was observed in iKsp-Pkd1(-/-) mice. In conclusion, our data indicate that PC1 is involved in renal Mg2+, Ca2+, and water handling and its dysfunction, resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations.