Abstract
Deep brain stimulation (DBS) is a powerful neurostimulation therapy proposed for the treatment of several neuropsychiatric disorders. However, DBS mechanism of action remains unclear, being its effects on brain dynamics of particular interest. Specifically, DBS reversibility is a major point of debate. Preclinical studies in obesity showed that the stimulation of the lateral hypothalamus (LH) and nucleus accumbens (NAcc), brain centers involved in satiety and reward circuits, are able to modulate the activity of brain structures impaired in this pathology. Nevertheless, the long-term persistence of this modulation after DBS withdrawal was unexplored. Here we examine the in vivo presence of such changes 1 month after LH- and NAcc-DBS, along with differences in synaptic plasticity, following an exploratory approach. Thus, both stimulated and non-stimulated animals with electrodes in the NAcc showed a common pattern of brain metabolism modulation, presumably derived from the electrodes’ presence. In contrast, animals stimulated in the LH showed a relative metabolic invariance, and a reduction of neuroplasticity molecules, evidencing long-lasting neural changes. Our findings suggest that the reversibility or persistence of DBS modulation in the long-term depends on the selected DBS target. Therefore, the DBS footprint would be influenced by the stability achieved in the neural network involved during the stimulation.
Highlights
Deep brain stimulation (DBS) is a powerful neurostimulation therapy proposed for the treatment of several neuropsychiatric disorders
We showed that lateral hypothalamus (LH)-DBS in a rat model of genetic obesity (Zucker rat) induced weight gain reductions and metabolic changes in brain regions related to the control of food intake[30]
The density of puncta expressing PSA-NCAM in the entorhinal cortex was significantly decreased in the layer III (p < 0.001) of LH-DBS animals when compared with sham animals (Fig. 5), while no significant changes were observed between nucleus accumbens (NAcc) groups
Summary
Deep brain stimulation (DBS) is a powerful neurostimulation therapy proposed for the treatment of several neuropsychiatric disorders. Preclinical studies in obesity showed that the stimulation of the lateral hypothalamus (LH) and nucleus accumbens (NAcc), brain centers involved in satiety and reward circuits, are able to modulate the activity of brain structures impaired in this pathology. From the early 50s to the late 70s, pioneer researchers such as Delgado, Bekthereva, Sem-Jacobsen and Cooper, first recognized the therapeutic potential of D BS1–3 It was not until 1987 that Benabid and Pollack d iscoveries[4] established DBS as an effective treatment for movement disorders. There is still no obvious evidence of the underlying phenomena, while the study of the neural consequences during and after DBS treatment seems crucial to spread its application to other pathologies In this sense, treatment-resistant obesity appears as a candidate disease to benefit from this t herapy[18]. Four clinical trials testing the efficacy of high frequency NAcc-DBS reported significant weight reductions in those patients who finished the follow-up p eriod[26,27,28,29]
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