Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study

Clinical and preclinical evidence suggests a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for novel therapeutic approaches to depression. The goal of this study was to compare mGluR5 binding (in a positron emission tomography [PET] study) and mGluR5 protein expression (in a postmortem study) between individuals with major depressive disorder and psychiatrically healthy comparison subjects

Reduced Metabotropic Glutamate Receptor 5 Density in Major Depression Determined by [11C]ABP688 Positron Emission Tomography and Postmortem Study

Objective: Clinical and preclinical evidence suggest a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for discovery of novel therapeutic approaches against depression. The goal of this study was to compare mGluR5 binding (PET study) and mGluR5 protein expression (postmortem study) between subjects with major depressive disorder and healthy controls. Method: Images of mGluR5 receptor binding were acquired using PET and [11C]ABP688 that binds to an allosteric site with high specificity in 11 unmedicated subjects with major depression and 11 matched healthy controls; the amount of mGluR5 protein was investigated using Western blot method in brain samples of 15 depressed subjects and 15 matched controls (postmortem study). Results: The PET study revealed decreased regional mGluR5 binding in the prefrontal cortex, the cingulate cortex, the insula, the thalamus and the hippocampus of the depressed individuals (uncorrected p<0.001). Severity of depression correlated negatively with mGluR5 binding in the hippocampus (cluster-level corrected p=0.029). The postmortem study showed reduced mGluR5 protein expression in the prefrontal cortex (Brodmann's area 10) in depression (p<0.014), while prefrontal mGluR1 protein expression was unchanged. Conclusions: The reductions in mGluR5 binding found in the depressed sample are compatible with reduced protein expression in postmortem tissue. Thus, both studies suggest that basal or compensatory changes in excitatory neurotransmission play roles in the pathophysiology of major depression

Complex network of channels beneath an Antarctic ice shelf

Ice shelves play an important role in stabilizing the interior grounded ice of the large ice sheets. The thinning of major ice shelves observed in recent years, possibly in connection to warmer ocean waters coming into contact with the ice-shelf base, has focused attention on the ice-ocean interface. Here we reveal a complex network of sub ice-shelf channels under the Fimbul Ice Shelf, Antarctica, mapped using ground-penetrating radar over a 100 km2 grid. The channels are 300–500 m wide and 50 m high, among the narrowest of any reported. Observing narrow channels beneath an ice shelf that is mainly surrounded by cold ocean waters, with temperatures close to the surface freezing point, shows that channelized basal melting is not restricted to rapidly melting ice shelves, indicating that spatial melt patterns around Antarctica are likely to vary on scales that are not yet incorporated in ice-ocean models