We used functional magnetic resonance imaging (fMRI) to investigate how performing formalized and improvised forms of praying changed the evoked BOLD response in a group of Danish Christians. Distinct from formalized praying and secular controls, improvised praying activated a strong response in the temporopolar region, the medial prefrontal cortex, the temporo-parietal junction and precuneus. This finding supports our hypothesis that religious subjects, who consider their God to be 'real' and capable of reciprocating requests, recruit areas of social cognition when they pray. We argue that praying to God is an intersubjective experience comparable to 'normal' interpersonal interaction.

Cerebral water accumulation was studied during induction of brain edema in dystrophin-null transgenic mice (mdx-␤geo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 (aquaporin-4) in astroglial end-feet surrounding capillaries (blood-brain barrier) and at the glia limitans (cerebrospinal fluidbrain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58% ؎ 2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55% ؎ 3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the blood-brain barrier and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema. Brain edema is associated with many intracranial neuropathological states, such as head trauma, ischemic brain injury, neoplasms, and metabolic diseases including systemic hyponatremia. Although much investigation has addressed the underlying molecular mechanisms and pathophysiology of brain edema, little is known about the regulation of water transport across the blood-brain barrier, the cerebrospinal fluid (CSF)-brain interface, and between extracellular and intracellular compartments in brain parenchyma.It is well recognized that the aquaporin family of water channel proteins is the major pathway by which water rapidly crosses cell membranes (1). Manley et al. recently reported that AQP4 (aquaporin-4; ref. 18) negatively influences the outcome from brain edema (2), and other recent studies also have suggested that AQP4 contributes to the development of brain edema (3, 4). These observations are consistent with the distribution of AQP4 in brain, because the protein is expressed abundantly in a highly polarized distribution in ependymal cells and astroglial membranes facing capillaries and forming the glia limitans (5).Decreased expression of AQP4 protein without changes in the AQP4 mRNA levels was reported recently in brains of Dmd mdx mice (C57BL10 ScSn mdx), a strain carrying a spontaneous mutation that prevents expression of the longest isoform of dystrophin (6)....

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Key points This is the first long‐term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology. NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle. NR supplementation does not affect NAD metabolite concentrations in skeletal muscle. Respiration, distribution and quantity of muscle mitochondria are unaffected by NR. NAMPT in skeletal muscle correlates positively with oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase. Abstract Preclinical evidence suggests that the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) boosts NAD+ levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle‐aged, obese, insulin‐resistant men affects mitochondrial respiration, content and morphology in skeletal muscle. In a randomized, placebo‐controlled clinical trial, 40 participants received 1000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high‐resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and quantitative PCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD+ biosynthetic enzyme in skeletal muscle, decreased by 14% with NR. However, steady‐state NAD+ levels as well as gene expression and protein abundance of other NAD+ biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin‐resistant men. Future studies on the effects of NR on human skeletal muscle may include both sexes and potentially provide comparisons between young and older people.