Date of Award
Bachelor of Science
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with marked loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). In PD, there are motor and non-motor symptoms. Depression, a non-motor symptom, is seen in 40% of the patients with PD which decreases their quality of life. For treatment-resistant depression, vagus nerve stimulation (VNS) has been shown to improve depression. Here, non-invasive focused ultrasound (FUS) is investigated as a therapeutic to improve depression-like behavior by targeting the celiac plexus since it is innervated by the vagus nerve. FUS was chosen due to its parallel mechanism to VNS. Male Sprague Dawley rats were used and made hemi-Parkinsonian (“PD”) with craniotomy surgery which delivered unilateral six-hydroxydopamine (6-OHDA) in the brain to lesion dopaminergic neurons in the right medial forebrain bundle (MFB). Sham (n=23) and Hemi-Parkinsonian (n=40) were evaluated using LATs to determine their forepaw movement. They underwent a sucrose preference test (SPT) to assess the rats’ level of anhedonia, or their inability to experience pleasure, which is one behavioral test that evaluates depression-like behavior in rats. FUS was delivered to the rats 21 days post-lesion for five consecutive days. Post-mortem analysis was performed using TH analysis. It was shown that hemi-Parkinsonian rats displayed akinesia in their left forepaw and a >90% reduction in dopaminergic neurons on the lesion side. It was found that hemi-Parkinsonian rats exhibited anhedonia which was improved with FUS treatment. The TH analysis displayed no statistical difference between the different treatment groups. In all, FUS improved anhedonia in hemi-Parkinsonian and sham rats which may be a credible therapeutic for future patients. While further research must be done, FUS may be viable therapeutics for patients with PD experiencing depression.
Berger, Hudy, "Improvement of Depressive-like Behaviors in Hemi-parkinsonian Rats with Non-invasive Peripheral Focused Ultrasound Modulation" (2023). Biological Sciences. 91.