Subthalamic Nucleus Deep Brain Stimulation Employs trkB Signaling for Neuroprotection and Functional Restoration

Fischer, D. Luke; Kemp, Christopher J.; Cole-Strauss, Allyson; Polinski, Nicole K.; Paumier, Katrina L.; Lipton, Jack W.; Steece‐Collier, Kathy; Collier, Timothy J.; Buhlinger, Daniel J.; Sortwell, Caryl E.

doi:10.1523/jneurosci.2060-16.2017

Cited by 44 publications

(42 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DBS also seems to change the neurochemical milieu of neurons and neuronal tissue (Gondard et al , ; Udupa & Chen, ; Fischer et al , ; Torres‐Sanchez et al , ). Although the immediate effects of DBS are an altered firing pattern of neural circuits, these are often followed by changes in neurotransmitter dynamics and protein expression, which inevitably affect the behavior of the network in the longer term (McIntyre & Hahn, ; Fig ).…”

Section: Neurochemical Effectsmentioning

confidence: 99%

“…Recently, neurotrophic mechanisms of STN-DBS neuroprotection have also been demonstrated in preclinical models of PD (Spieles-Engemann et al, 2010;Fischer et al, 2017;Fischer & Sortwell, 2018). Specifically, in vivo studies showed that STN-DBS promotes expression of BDNF in the basal ganglia, which in turn binds to the tropomyosin-related kinase type 2 (trkB) receptor.…”

Section: Neurogenesis Synaptogenesis and Neuroprotectionmentioning

confidence: 99%

“…As the chief BDNF and neurotropin-3 receptor in the basal ganglia, trkB has intermediate and long-term downstream effects including promoting dopaminergic neuron survival (Baydyuk et al, 2011), regulating synaptic plasticity (Leal et al, 2014), and maintenance of the nigrostriatal pathway as a whole (Baydyuk et al, 2011;Fischer et al, 2017). Increased BDNF was seen with high-frequency electrical stimulation of cultured dopaminergic neurons (Hartmann et al, 2001), as well as STN-DBS of PD rodent models (Fischer et al, 2017), with long-lasting neuroprotective benefits in the latter even after discontinuation of stimulation. Similarly, studies of STN-DBS in non-human primate models of PD have shown potential neuroprotective effects via inhibition of excitotoxic cell death (Tsukahara et al, 1995).…”

Section: Neurogenesis Synaptogenesis and Neuroprotectionmentioning

confidence: 99%

See 2 more Smart Citations

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

et al. 2019

View full text Add to dashboard Cite

Deep brain stimulation ( DBS ) has been successfully used to treat movement disorders, such as Parkinson's disease, for more than 25 years and heralded the advent of electrical neuromodulation to treat diseases with dysregulated neuronal circuits. DBS is now superseding ablative techniques, such as stereotactic radiofrequency lesions. While serendipity has played a role in developing DBS as a therapy, research during the past two decades has shown that electrical neuromodulation is far more than a functional lesion that can be switched on and off. This understanding broadens the field to enable new types of stimulation, clinical indications, and research. This review highlights the complex effects of DBS from the single cell to the neuronal network. Specifically, we examine the electrical, cellular, molecular, and neurochemical mechanisms of DBS as applied to Parkinson's disease and other emerging applications.

show abstract

Section: Neurochemical Effectsmentioning

confidence: 99%

Section: Neurogenesis Synaptogenesis and Neuroprotectionmentioning

confidence: 99%

Section: Neurogenesis Synaptogenesis and Neuroprotectionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In this case, upregulation of TrkB mRNA by genistein may be viewed as a turning on switch for the interaction of BDNF with its neuroreceptor [34], thereby supplying a compensatory ability of limbic cells to cope with reduced levels of BDNF-TrkB complex deriving from stressful conditions [35] in a comparable manner to its antidepressant effects [36] exhibited especially during the functional restoration of pathologies such as Parkinson’s disease [37]. …”

Section: Discussionmentioning

confidence: 99%

Genistein Modifies Hamster Behavior and Expression of Inflammatory Factors following Subchronic Unpredictable Mild Stress

et al. 2018

View full text Add to dashboard Cite

Background: Previous studies have pointed to the protective role of genistein against stress adaptations although neuromolecular mechanisms are not yet fully known. With this work, we evaluated the influence of such a phytoestrogen on hamster behavioral and molecular activities following exposure to subchronic unpredictable mild stress. Methods: The motor behaviors of hamsters (n = 28) were analyzed using elevated plus maze (EPM) test, hole board (HB) test, and forced swim test (FST). In addition, neurodegeneration events were assessed with amino cupric silver stain, while expression variations of tropomyosin receptor kinase B (TrkB), nuclear factor kappa-B1 (NF-κB1), and heat shock protein 70 (Hsp70) mRNAs were highlighted in limbic neuronal fields via in situ hybridization. Results: Genistein accounted for increased motor performances in EPM and HB tests but reduced immobility during FST, which were correlated with diminished argyrophilic signals in some limbic neuronal fields. Contextually, upregulated Hsp70 and TrkB mRNAs occurred in hippocampal (HIP) and hypothalamic neuronal fields. Conversely, diminished NF-κB1 levels were mainly obtained in HIP. Conclusion: Hormonal neuroprotective properties of genistein corroborating anxiolytic and antidepressant role(s) through elevated expression levels of stress proteins and trophic factors may constitute novel therapeutic measures against emotional and stress-related motor performances.

show abstract

“…55,56 More recent evidence supports a neurotrophic mechanism of neuroprotection by STN DBS, specifically via increased levels of BDNF. 8,10 Specifically, BDNF release can be driven through electrical stimulation. In neuronal cultures, high-frequency stimulation leads to increased BDNF release.…”

Section: The Role Of Bdnf In Stn Dbs-mediated Disease Modificationmentioning

confidence: 99%

BDNF provides many routes toward STN DBS‐mediated disease modification

Fischer

Sortwell

2018

Movement Disorders

Self Cite

View full text Add to dashboard Cite

A BS TRACT: The concept that subthalamic nucleus deep brain stimulation (STN DBS) may be disease modifying in Parkinson's disease (PD) is controversial. Several clinical trials that enrolled subjects with late-stage PD have come to disparate conclusions on this matter. In contrast, some clinical studies in early-to midstage subjects have suggested a disease-modifying effect. Dopaminergic innervation of the putamen is essentially absent in PD subjects within 4 years after diagnosis, indicating that any neuroprotective therapy, including STN DBS, will require intervention within the immediate postdiagnosis interval. Preclinical prevention and early intervention paradigms support a neuroprotective effect of STN DBS on the nigrostriatal system via increased brain-derived neurotrophic factor (BDNF). STN DBSinduced increases in BDNF provide a multitude of mechanisms capable of ameliorating dysfunction and degeneration in the parkinsonian brain. A biomarker for measuring brain-derived neurotrophic factor-trkB signaling, though, is not available for clinical research. If a prospective clinical trial were to examine whether STN DBS is disease modifying, we contend the strongest rationale is not dependent on a preclinical neuroprotective effect per se, but on the myriad potential mechanisms whereby STN DBS-elicited brain-derived neurotrophic factor-trkB signaling could provide disease modification.

show abstract

Subthalamic Nucleus Deep Brain Stimulation Employs trkB Signaling for Neuroprotection and Functional Restoration

Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common neurosurgical treatment for

Cited by 44 publications

References 58 publications

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

Genistein Modifies Hamster Behavior and Expression of Inflammatory Factors following Subchronic Unpredictable Mild Stress

BDNF provides many routes toward STN DBS‐mediated disease modification

Contact Info

Product

Resources

About