7 research outputs found
Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy
Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy
Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy
The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice
Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Clâ in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Clâ/HCO3â exchanger (NDCBE/SLC4A8) and the Na+-independent Clâ/HCO3â exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice
Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
Firstâdegree relatives of patients diagnosed with schizophrenia (SZâFDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. Firstâdegree relatives of patients diagnosed with bipolar disorder (BDâFDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BDâFDRs are inconsistent. Here, we performed a metaâanalysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZâFDRs, 867 BDâFDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZâFDRs showed a pattern of widespread thinner cortex, while BDâFDRs had widespread larger cortical surface area. IQ was lower in SZâFDRs (d = â0.42, p = 3âĂâ10â5), with weak evidence of IQ reductions among BDâFDRs (d = â0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the groupâeffects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZâFDRs and more pronounced effects in BDâFDRs. To conclude, SZâFDRs and BDâFDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZâFDRs and BDâFDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment