Progressive brain metabolic changes under deep brain stimulation of subthalamic nucleus in parkinsonian rats

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient neurosurgical treatment for advancedParkinson's disease. Non-invasive metabolic neuroimaging during the course of DBS in animal models may contribute to our understanding of its action mechanisms. Here, DBS was adapted to in vivo proton magnetic resonance spectroscopy at 11.7 T in the rat to follow metabolic changes in main basal ganglia structures, the striatum, and the substantia nigra pars reticulata (SNr). Measurements were repeated OFF and ON acute and subchronic (7 days) STN-DBS in control and parkinsonian (6-hydroxydopamine lesion) conditions. Acute DBS reversed the increases in glutamate, glutamine, and GABA levels induced by the dopamine lesion in the striatum but not in the SNr. Subchronic DBS normalized GABA in both the striatum and SNr, and glutamate in the striatum. Taurine levels were markedly decreased under subchronic DBS in the striatum and SNr in both lesioned and unlesioned rats. Microdialysis in the striatum further showed that extracellular taurine was increased. These data reveal that STN-DBS has duration-dependent metabolic effects in the basal ganglia, consistent with development of adaptive mechanisms. In addition to counteracting defects induced by the dopamine lesion, prolonged DBS has proper effects independent of the pathological condition.

Deep brain stimulation mechanisms: the control of network activity via neurochemistry modulation

“…Melon et al . ). In addition, computational models are beginning to integrate these types of experimental results into unifying hypotheses (e.g.…”

“…Recent studies of rodent neurochemistry modulation with DBS have turned to in vivo proton magnetic resonance spectroscopy and begun to address key questions on the effects of chronic stimulation (Melon et al . ; Chassain et al . ).…”

“…Recent studies of rodent neurochemistry modulation with DBS have turned to in vivo proton magnetic resonance spectroscopy and begun to address key questions on the effects of chronic stimulation (Melon et al 2015;Chassain et al 2016). Results from these studies show that chronic (5 week) continuous subthalamic DBS efficiently counteracts the metabolic and synaptic defects that arise from dopaminergic lesion, which include significant increases in both glutamate and GABA in the striatum and SN.…”

Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals

“…Although this model is known to reflect the major behavioral impairments that are characteristic of PD patients, animal studies are hampered by restrictions on free movement and/or invasive surgery and by short observation periods lasting from a few minutes [35, 49, 51–54] to a number of days [12, 24, 55–57]. To our knowledge, removable and reusable devices have been previously used by only Forni et al [28].…”

“…According to this view, a lesion-induced reduction in glutamate release to the cortex and the striatum resulting from alterations in activity along the striatum-D1 receptor-EP/SNr-thalamus pathway will result in an upregulation in glutamate receptors in the cortex and striatum. However, DBS after lesioning was found to reverse the increased striatal glutamate receptor numbers [57] and to increase the number of D1 receptors, which probably improves motor symptoms in PD patients [74]. At the same time, DBS decreases the number of D2/D3 receptors in the nucleus accumbens of rats, which may contribute to adverse DBS-induced neuropsychiatric side effects, such as apathy [74].…”