ABSTRACT
BACKGROUND: Translational studies investigating the effects of deep brain stimulation (DBS) on brain function up to now mainly relied on BOLD responses measured with fMRI. However, fMRI studies in rodents face technical and practical limitations (e.g., immobilization, sedation or anesthesia, spatial and temporal resolution of data). Direct measurement of oxygen concentration in the brain using electrochemical sensors is a promising alternative to the use of fMRI. Here, we tested for the first time if such measurements can be combined with DBS. NEW METHOD: We combined bilateral DBS in the internal capsule (IC-DBS) with simultaneous amperometric measurements of oxygen in the medial prefrontal cortex (prelimbic area) and striatum of freely moving mice. Using a two-day within-animal experimental design, we tested the effects of DBS on baseline oxygen concentrations, and on novelty- and restraint-induced increases in oxygen concentration. RESULTS: Basal oxygen levels were stable across the daily sampling periods. Exposure to novelty and immobilization reproducibly increased oxygen concentrations in both areas. IC-DBS did not significantly alter basal oxygen, but reduced the novelty-induced increase in the striatum. COMPARISON WITH EXISTING METHOD(S): Amperometric detection of brain oxygen concentration with high temporal and spatial resolution can be performed in a number of key brain areas to study the effects of DBS in animal models of disease. The method is easily implemented and does not require expensive equipment or complicated data analysis processes. CONCLUSIONS: Direct and simultaneous measurement of brain oxygen concentration in multiple brain areas can be used to study the effects of bilateral DBS neuromodulation on brain activity in freely moving mice.
Subject(s)
Biosensing Techniques/methods , Corpus Striatum/metabolism , Deep Brain Stimulation , Oxygen/analysis , Prefrontal Cortex/metabolism , Animals , Behavior, Animal , Biosensing Techniques/instrumentation , Internal Capsule/physiology , Male , Mice, Inbred C57BL , Oxygen/metabolismABSTRACT
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC.
Subject(s)
Anxiety/therapy , Brain/physiopathology , Deep Brain Stimulation , Animals , Anxiety/physiopathology , Caudate Nucleus/physiopathology , Conditioning, Classical , Internal Capsule/physiopathology , Male , Maze Learning/physiology , Motor Activity/physiology , Nucleus Accumbens/physiopathology , Rats , Rats, WistarABSTRACT
The hypothesis was tested that dying tumor cells release spermidine and putrescine into the bloodstream. Therefore, a rhabdomyosarcoma was implanted in rats, irradiated and its growth and subsequent reduction compared with spermidine and putrescine plasma concentrations of the venous effluent from the tumor side and contralateral side. In the experimental set-up used the hypothesis could not be verified. It appeared that irradiation only, implantation and growth of a tumor only and an irradiated tumor, all caused elevated spermidine and putrescine concentrations in the effluent of both sides in approximately the same order of magnitude, compared to untreated controls.
