Parkinson’s attacks the mind, body, and the spirit. Hope treats all three.
- Gordon Adai
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. One out of every 100 people over the age of 60 develops PD, a number which will only rise as the average life span increases. [1]
Symptoms of Parkinson’s
Many signs of Parkinson’s disease are commonly recognized and visible to other people. These include tremors, slowed movement, muscle rigidity, problems with posture and balance. Other symptoms are less evident. Constipation and anxiety that are related to PD can begin occurring years before other symptoms appear.
Limited treatments exist, which target
symptoms of the disease, but there is currently
no cure available.
PD is related to inhibited dopamine production. PS128 has been shown to modulate dopamine levels in preclinical models. Therefore, scientists tested whether or not PS128 could benefit mice with reduced dopamine production and resulting movement disability. Positive results, as described below, have led to clinical study of Parkinson’s patients given PS128.
Study on Mice with PD-like Symptoms
Summary
One group of mice were injected with MPTP, a molecule that destroys dopamine-producing neurons. This mimicked the necrosis of these cells as seen in the etiology of Parkinson’s disease, consequently inducing PD symptoms. One portion of these MPTP mice was fed PS128 daily and a second was given a saline placebo. Another cohort was not given MPTP but received only PS128, while a final control group was given only saline. The experiment lasted 28 days.
Results
Research confirmed that treatment with PS128 resulted in dopaminergic neuron protection, effectively preventing the pathophysiological damage like that seen in Parkinson’s. The psychobiotic enhanced the mice’s physical activity and coordination and ameliorated their movement and balance disorders.
01
PS128 offers neuroprotection (rescues dopaminergic neurons).
Neurons in the substantia nigra (SN) and the striatum were stained with immuno-fluorescence and the tyrosine hydroxylase-positive cells were visualized. Tyrosine kinase is an enzyme that is involved in the synthesis of dopamine. MPTP mice fed with PS128 are shown to have higher levels of tyrosine hydroxylase activity compared to MPTP mice fed with saline, suggesting neuroprotection activity of PS128 in the Parkinson’s disease mice model.
02
Movement speed and control increased.
In experimental mice, MPTP induces PD-like symptoms such as slow movement and balance impairment. During the pole-climbing experiment, test mice climbed from the top down to the bottom of a pole. Their activity level and speed were recorded, with normal mice taking less than 10 seconds to complete the task. The MPTP mice with only saline treatment climbed down sluggishly, their limbs uncoordinated, taking around 40 seconds to reach the bottom, while their PS128-treated counterparts took on average only 15 seconds. The test showed that PS128 can improve mobility and grip strength, reversing MPTP-induced sluggishness.
03
Balance was improved.
Normal mice can cross a narrow beam 100 cm long in under 10 seconds. During the experiment, the MPTP-saline cohort walked unsteadily, their limbs weak and tails unable to assist in maintaining balance. As a result, they spent more than 30 seconds crossing the beam. On the other hand, the MPTP mice that received PS128 moved with ease, tails lifted high, crossing steadily in less than 20 seconds. PS128 has the potential to improve movement and balance disorders.
[1] Tysnes, O. B., & Storstein, A. (2017). Epidemiology of Parkinson's disease. Journal of neural transmission (Vienna, Austria : 1996), 124(8), 901–905.
04
PS128 elevates antioxidant enzymes (to prevent mitochondrial damage).
Oxidative agents such as free radicals may cause mitochondrial damage in neurons, resulting in oxidative stress within the cell. In this study, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and Glutathione are tested as the antioxidant enzymes. MPTP mice administered with PS128 showed significantly higher levels of SOD, CAT, Glutathione peroxidase, and Glutathione enzyme activity compared to mice administered with saline only.
05
PS128 suppresses inflammatory cytokines in striatum
Tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 are cytokines that would attract immune cells to the intruded region, triggering an immune response such as inflammation. Thus, cytokines may act as biomarkers for inflammation. In this study, MPTP mice fed with PS128 showed significantly lower levels of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in the striatum compared to MPTP mice treated with saline only.
06
PS128 suppresses MPTP-induced neuroinflammation in striatum
MPTP is a neurotoxin prodrug, which means that when MPTP is injected into the brain, it is converted into the neurotoxin MPP+ and destroys dopaminergic neurons. Glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) are protein glial markers which may indicate neuroinflammation. MPTP rodents administered with PS128 showed significantly reduced GFAP and Iba1 in striatum compared to MPTP mice fed with saline, something that MPTP mice treated with L-DOPA (Levodopa) also failed to achieve.
07
PS128 suppresses Enterobacteriaceae (associated with inflammation and less antioxidant)
Enterobacteriaceae is a family of gut bacteria associated with inflammation and less antioxidant activity. This can be seen in graphs (B) and (C), where Enterobacteriaceae density is positively associated with TNF-α in midbrain, and Enterobacteriaceae density is negatively associated with SOD in midbrain, respectively. When MPTP mice were administered with PS128, significantly reduced levels of Enterobacteriaceae in fecal samples was observed compared to MPTP mice administered with saline as control, suggesting PS128’s role in the suppression of Enterobacteriaceae.
