Noninvasive Ultrasound Deep Brain Stimulation for the Treatment of Parkinson’s Disease Model Mouse

Abstract

<jats:p>Modulating basal ganglia circuitry is of great significance in the improvement of motor function in Parkinson’s disease (PD). Here, for the first time, we demonstrate that noninvasive ultrasound deep brain stimulation (UDBS) of the subthalamic nucleus (STN) or the globus pallidus (GP) improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunohistochemical c-Fos protein expression confirms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group (both p &lt; 0.05). Furthermore, STN-UDBS or GP-UDBS significantly increases the latency to fall in the rotarod test on day 9 (p &lt; 0.05) and decreases the time spent climbing down a vertical rod in the pole test on day 12 (p &lt; 0.05). Moreover, our results reveal that STN-UDBS or GP-UDBS protects the dopamine (DA) neurons from MPTP neurotoxicity by downregulating Bax (p &lt; 0.001), upregulating Bcl-2 (p &lt; 0.01), blocking cytochrome c (Cyt C) release from mitochondria (p &lt; 0.05), and reducing cleaved-caspase 3 activity (p &lt; 0.01) in the ipsilateral substantia nigra (SN). Additionally, the safety of ultrasound stimulation is characterized by hematoxylin and eosin (HE) and Nissl staining; no hemorrhage or tissue damage is detected. These data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice, potentially serving as a noninvasive strategy for the clinical treatment of PD.</jats:p>

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…However, apomorphine is a remarkable drug that is extensively used for stimulating motor functions in PD. Non-pharmacological treatments like deep brain stimulation and acupuncture have been used to improve motor function in PD patients [ 133 , 156 ]. In accordance with the above-cited literature, the midforebrain lesion type is more effective in causing neurodegeneration and the symptoms compared to other administrative methods in animal models of PD.…”

“…Subthalamic nucleus/globus pallidus-ultrasound deep brain stimulation increased the latency to fall in the rotarod test on the 9th day and reduced the pole test time on the 12th day. Their data also showed that the ultrasound deep brain stimulation protected the dopaminergic neurons by reducing antiapoptotic expression [ 156 ]. The drug dose, lesion type, and behavioral evaluating methods in each MPTP-induced PD animal model are summarized in Table 3 .…”

Nonhuman Primate Model of Oculocutaneous Albinism with TYR and OCA2 Mutations

“…Because of their high genomic homology and similar anatomical eye structure and ontogenetic development of the fovea to humans, rhesus macaques present great potential as models for studying OCA and other neurological disorders [32,33,[37][38][39][40]. In this study, we identified rhesus macaque models that were characterized by classical ocular characteristics comparable to those of OCA patients, including nystagmus, retinal hypopigmentation, and foveal hypoplasia.…”

Biomarkers and neuromodulation techniques in substance use disorders

“…Implanted probes delivering focal cooling or heating have been demonstrated to decrease or respectively increase the excitability of surrounding cortical structures (Chen et al 2015;Fujioka et al 2010). Focused ultrasound can be delivered non-invasively via wearable probes and has been shown to modulate neural activity in basal ganglia in mice (Zhou et al 2019). Optogenetic stimulation without penetrating optical probes has also been recently made possible using nanoparticle mediated upconversion of infrared light (Chen et al 2018).…”