Coenzyme Q10, an antioxidant supplement that, when taken orally, has shown limited effectiveness, can alleviate Parkinson’s disease symptoms when injected directly into the brain, a study in rats suggests.
The study, “Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson’s disease rat model,” was published in Scientific Reports.
Parkinson’s disease is characterized by the death of dopamine-producing (dopaminergic) neurons in the brain, specifically affecting a brain region called the striatum. It is believed that this neuronal death is driven by oxidative stress, which is an imbalance between the production and clearance of toxic reactive species that are harmful to cells.
Antioxidants — substances that clear out these toxic molecules — may have therapeutic value in Parkinson’s. Coenzyme Q10 (CoQ10), an antioxidant that is found naturally in the body, has garnered some interest for this purpose. However, when taken by mouth, very little of the antioxidant reaches the striatum, limiting its effects.
In the new study, researchers in Korea tested whether injecting CoQ10 directly into the striatum would achieve better therapeutic effects than oral administration in a rat model of Parkinson’s.
Parkinson’s rats were established by treating them with 6-hydroxydopamine, a chemical that kills dopamine-producing neurons similarly to what happens in Parkinson’s. They were divided into five groups. One group received no treatment, one was given oral CoQ10 (at a dose of greater than 45 mg per day), one was outfitted with striatum-injecting pumps without CoQ10, and two groups were outfitted with striatum-injecting pumps that injected CoQ10 at one of two doses (about 1.8 and 2.6 micrograms per day).
The rats’ behavior was assessed with a rotation test; in this test, rats with more dopaminergic neuron damage will rotate more times. In untreated rats, the number of rotations gradually increased from four to seven weeks. In rats given oral CoQ10, the number of rotations plateaued such that, by weeks six and seven, they rats had significantly fewer rotations than untreated rats.
“This delayed efficacy could be attributed to the delayed increase in CoQ10 concentration in the brain that is often observed with oral administration of CoQ10,” the researchers wrote.
Rats injected with the lower dose of intrastriatal CoQ10 generally had fewer rotations than the untreated group, but the difference was statistically significant only on weeks five and six. Rats injected with the higher dose of CoQ10 had significantly fewer rotations than untreated rats at all time points measured.
Notably, the overall dose administered for the highest injection dose is about 17,000 times lower than the overall oral dose, “implying very high bioavailability of intrastriatally delivered CoQ10,” the researchers wrote.
The researchers assessed dopaminergic neurons in biopsied brains from the rats. In untreated rats, almost all dopaminergic neurons were dead by week seven. Rats given oral CoQ10 had some protection of these neurons, but rats given the higher dosage intrastriatal injection of CoQ10 had markedly greater neuronal protection.
“These results indicated that intrastriatally delivered CoQ10 had a significant neuroprotective effect, which was more prominent than that of orally administered CoQ10 at a very high dose,” the researchers wrote.
Furthermore, rats that received CoQ10 into the brain had significantly higher levels of molecules associated with neural and blood vessel growth, whereas they had lower levels of the inflammatory molecule tumor necrosis factor alpha, than untreated rats. Oral CoQ10 generally did not significantly affect levels of the molecules assessed; when there was a significant effect, it was of a markedly lesser magnitude than injected CoQ10.
“Although invasive, the strategy of intrastriatal CoQ10 delivery may still enable high bioavailability in the target site, which could eventually achieve therapeutic efficacy in the prevention of Parkinson’s disease progression,” the researchers concluded.
“CoQ10 is known to elicit effects in models of other neurodegenerative diseases, such as Huntington’s disease, progressive supranuclear palsy, and Alzheimer’s disease. Therefore, the intrastriatal delivery of CoQ10 described herein is a promising strategy to prevent the progression of various neurodegenerative diseases, including Parkinson’s disease,” they added.
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