Clues to how deep brain stimulation may alleviate depression

Posted by Biome on 3rd March 2014 - 0 Comments


Magnetic stimulation of the scalp is thought to influence neural activity of the brain and has been used in the successful treatment of depression, becoming approved for use in the US in 2008. More invasive deep brain magnetic stimulation (DMS) has also been used in patients with severe neuropsychiatric disorders, including Parkinson’s, however, the biological basis of electrostimulation as a therapeutic approach remains poorly understood. The adult neurogenesis hypothesis of depression suggests that recovery is marked by neural growth in the dentate gyrus of the hippocampus. A recent study in Molecular Brain now explores how DMS affects hippocampal neurons and other markers of depression in rodents.

Under microscopic examination of the hippocampus of wild type mice, Zilong Qiu from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China, and colleagues found that DMS treatment resulted in neural stem cell proliferation and promoted dendrite growth in both adult and senescent animals. These striking morphological findings are supplemented by data showing the upregulation of marker genes for neural activity, including the hippocampal Fgf1b gene that is known to be induced by electroconvulsive stimulation.

Additional behavioral studies found that DMS could rescue an experimentally induced depressed phenotype in mice – an effect that was shown to depend upon growth of new hippocampal neurons, by using gamma irradiation to experimentally knock out neural proliferation. Recovery under DMS treatment was accompanied by restoration of MKP-1, a gene that is dysregulated during depression. Furthermore, an electrophysiological study of rats undergoing restraint stress (a model for psychosocial stress) revealed a recovery of axonal long-term potentiation to non-depressed levels under DMS treatment. This latter finding, alongside the changes that were already demonstrated in neural gene activity, suggests that DMS plays a role in modulating synaptic plasticity. Lastly, DMS was shown to reverse the anxiety phenotype and, somewhat surprisingly, extend lifespan in a mouse model of the neurodevelopmental disorder, Rett syndrome.

The effect of DMS treatment on neuronal growth and activity, in the adult rodent hippocampus, provides a novel biological evidence base for electrostimulation that merits further investigation to help treat neuropsychiatric disorders. The observations that DMS reverses several molecular, physiological and behavioral correlates of depression in rodent models deepens our knowledge of the pathophysiology of depressive disease in particular, and strengthens support for the use of electrostimulation to treat depression in humans.