No abstract

Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain longterm axonal integrity [1][2][3] . However, the underlying support mechanisms are not understood 4 . Here we identify ametabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors 5 , postmyelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations inmutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Becausemyelinated axons can use lactate when energy-deprived 6 , our findings suggest a model in which axon-glia metabolic coupling serves a physiological function. † Present

The reconstruction of artifact-free images from radially encoded MRI acquisitions poses a difficult task for undersampled data sets, that is for a much lower number of spokes in k-space than data samples per spoke. Here, we developed an iterative reconstruction method for undersampled radial MRI which (i) is based on a nonlinear optimization, (ii) allows for the incorporation of prior knowledge with use of penalty functions, and (iii) deals with data from multiple coils. The procedure arises as a twostep mechanism which first estimates the coil profiles and then renders a final image that complies with the actual observations. Prior knowledge is introduced by penalizing edges in coil profiles and by a total variation constraint for the final image

Stress-induced structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis, provides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of structural remodeling may be a desirable goal for antidepressant therapy. The present study investigated the effect of tianeptine, a modified tricyclic antidepressant, in the chronic psychosocial stress model of adult male tree shrews (Tupaia belangeri), a model with high validity for research on the pathophysiology of major depression. Animals were subjected to a 7-day period of psychosocial stress to elicit stress-induced endocrine and central nervous alterations before the onset of daily oral administration of tianeptine (50 mg͞kg). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy, cell proliferation in the dentate gyrus was quantified by using BrdUrd immunohistochemistry, and hippocampal volume was measured post mortem. Chronic psychosocial stress significantly decreased in vivo concentrations of N-acetyl-aspartate (؊13%), creatine and phosphocreatine (؊15%), and choline-containing compounds (؊13%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (؊33%). These stress effects were prevented by the simultaneous administration of tianeptine yielding normal values. In stressed animals treated with tianeptine, hippocampal volume increased above the small decrease produced by stress alone. These findings provide a cellular and neurochemical basis for evaluating antidepressant treatments with regard to possible reversal of structural changes in brain that have been reported in depressive disorders.neurogenesis ͉ proton magnetic resonance spectroscopy ͉ depression ͉ hippocampus ͉ tree shrew D epressive disorders are among the most common and lifethreatening illnesses and represent a significant public health problem (1). Despite extensive preclinical and clinical investigations, the exact neurobiological processes leading to depression and the mechanisms responsible for the therapeutic effects of antidepressant drugs are not completely understood (2).The hippocampus is one of the brain structures that has been extensively studied with regard to the actions of stress, depression and antidepressant actions (3, 4). Recent imaging studies in humans revealed that the hippocampus undergoes selective volume reduction in stress-related neuropsychiatric disorders such as recurrent depressive illness (5-7). Within the hippocampal formation, the dentate gyrus is one of the few brain structures where production of new neurons occurs even in the adult mammalian brain (8-10). Several experiential, neuroendocrine, and genetic factors that regulate neurogenesis in the adult dentate gyrus have been identified (11). One factor that potently suppresses adult granule cell prolife...