Effects of Ultrasound on Behavior and Dopamine Content in Striatum of Parkinson's Disease Model Mouse

Abstract

Abstract. In this research, we established a MPTP mouse model of PD, then ultrasound was used to stimulate the model to explore the effects of ultrasound on behavior and dopamine content in striatum. With the prolongation of ultrasonic stimulation time, the delay of observation time, the amount of DA in the striatum of the ultrasonic treatment group was increasing. Using ultrasound with a frequency of 1 MHz at an intensity of 0.3W/cm 2 over 15min for 1d, 5d or 10d respectively, in each group, there was a significant difference in the content of DA in the striatum compare to PD observation group at the same observation time(P<0.05). Especially, the DA content in the striatum of the mice treated with the ultrasound for 10 d was not statistically significant compared with the control group(P>0.05). Combined with the results of climbing test and open field test and general behavioral changes, the difference between ultrasound group and PD group reached a significant level (P<0.05). In summary, ultrasound can increase the DA content in the brain and improve the motor capacity of PD model. It suggests that ultrasound may be a safe and effective new method of PD treatment. IntroductionParkinson's disease (PD) is a common neurodegenerative disorder characterized by the reduce of the striatal DA level, which is related to the degeneration, death and deletion of dopaminergic neurons in the substantia nigra pars compacta (SNc), as well as the decrease of dopamine biosynthesis ability of the surviving neurons [1][2][3]. A series of clinical symptoms including resting tremor, rigidity, bradykinesia and postural instability will appear when DA content is lower than 70%. The gold standard for the treatment of PD is Levodopa therapy, which is aimed at increasing the availability of striatal dopamine and typically result in a brisk symptomatic improvement in most PD patients. Unfortunately, this response becomes less reliable and less predictable over time, medication related complications such as dyskinesia and "on-off" fluctuations develop in a majority of patients [4]. Because of the side effect of Levodopa therapy, researchers started to explore new therapies for PD.Ultrasound, as a new physical therapy, has been shown to be an effective neuronal activity regulator. William et al [5] experiments found that ultrasound on the cat's lateral geniculate body can inhibit the visual cortex evoked potential. Bauer et al [6] in the study results confirmed that after the end of ultrasound intervention in patients with tremor ease, six months after treatment and the Webster score was significantly improved. Wang et al found that GDNF levels were increased in the striatum of PD rats after lipid-coated GDNF microspheres administration following low frequency ultrasound stimulation (20kHz, 5min per day, daily for 4weeks). Moreover, GDNF microspheres reduced apomorphine-induced rotations, and increased striatal dopamine and nigral tyrosine hydroxylase (TH) levels in PD rats. In this research, we established a MPTP mouse model of PD, then u...

The effect and mechanism of low intensity focused ultrasound in the treatment of Parkinson's disease

“…Wang (Wang et al, 2017) et al demonstrated that ultrasound irradiation of MPTP model mice with the frequency of 1MHz and power of 0.3W/cm 2 over 15min for 10 days can improve the motor capacity and increase the DA content in the striatum. Zhou (Zhou, Niu, & Meng et al, 2019) et al used the MPTP mouse model of PD to demonstrate that noninvasive ultrasound deep brain stimulation (UDBS) of the STN or the globus pallidus (GP) improves motor behavior improved motor functioning and protected DA neurons through antiapoptotic effects.…”

“…These genus-based models (MPTP and 6-OHDA) are typically used to study the causes of dopamine loss in the neurons of the SN pars compacta and the striatum. To modulate α-synuclein aggregation in the brain, A53T α-syn mice and wild-type α-syn mice can be used (Wang et al, 2017;Xhima et al, 2018). Different types of animal models respond differently to the injection of varying molecular weight compounds, such as anti-syn antibody (Xhima et al, 2018), neurturin and Nrf2 (Long et al, 2017) into the brain parenchym (Table 2; Fig 1).…”

Improved alpha-beta power reduction via combined electrical and ultrasonic stimulation in a parkinsonian cortex-basal ganglia-thalamus computational model

“…Here, the potential application of transcranial LILFU for non-invasive DBS has been considered before [4,11,13,18]. Furthermore, recent in vivo studies in MPTP (1-methyl-4-fenyl-1,2,3,6tetrahydropyridine) lesioned parkinsonian mice have demonstrated ultrasound-induced striatal dopamine normalization [19,20], restored locomotion activity (open field test, pole test) [19][20][21][22], and an increase in striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) (neuroprotective antioxidant enzymes) [21]. Moreover, ultrasound focused at the STN or globus pallidus (GP) downregulates the Bax to Bcl-2 ratio (Bax and Bcl-2 are proapoptotic and antiapoptotic, respectively), resulting in a reduction of cleaved-caspase 3 activity in the substantia nigra [22].…”

Improved alpha-beta power reduction via combined Electrical and Ultrasonic stimulation in a Parkinsonian Cortex-Basal Ganglia-Thalamus Computational Model

“…Here, the potential application of transcranial LILFU for non-invasive deep brain stimulation has been considered before [4], [11]- [13], [18]. Furthermore, recent in vivo studies in MPTP (1-methyl-4-fenyl-1,2,3,6tetrahydropyridine) lesioned Parkinsonian mice have demonstrated ultrasound-induced striatal dopamine normalization [19], [20], restored locomotion activity (open field test, pole test) [19]- [22], and an increase in striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) (neuroprotective antioxidant enzymes) [21]. Moreover, ultrasound focused at the STN or globus pallidus (GP) downregulates the Bax to Bcl-2 ratio (Bax and Bcl-2 are proapoptotic and antiapoptotic, respectively), resulting in a reduction of cleaved-caspase 3 activity in the substantia nigra [22].…”