Delivering a compound called nicotinamide adenine dinucleotide to the striatum, a key brain region involved in motor control, can ease Parkinson’s symptoms and reduce dopamine-producing neuronal loss in a mouse model of the disease, a study finds.
The study, “Protective effects of β-nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson’s disease,” was published in Progress in Neuropsychopharmacology & Biological Psychiatry.
Found in all living cells, nicotinamide adenine dinucleotide (NAD) is a coenzyme — or a substance that enhances the action of an enzyme — used for a series of body functions, including cellular respiration.
Although its Parkinson’s trigger remains to be identified, research indicates the causative mechanisms involve genetics, nonworking mitochondria (cells’ “powerhouses”) and oxidative stress — an imbalance between the production of free radicals and the ability of cells to detoxify them. Taken together, these molecular and cellular changes eventually cause the death of dopamine-producing neurons — the type of nerve cell that is gradually lost in Parkinson’s disease.
“In particular, it has been found that a reduced level of nicotinamide adenine dinucleotide (NAD) may cause mitochondrial dysfunction, DNA repair defects and neuronal death, resulting in many age-associated neurodegenerative pathologies,” the researchers said. That means that, in theory, restoring NAD levels could prevent the loss of dopamine-releasing neurons.
A Chinese team of researchers investigated whether an NAD injection into the striatum could alleviate Parkinson’s motor deficits and reduce dopaminergic neural loss in a rodent model of the disease.
Animals were given a NAD injection into the right striatum four hours before being injected with a neurotoxin called 6-hydroxydopamine (6-OHDA) into the same brain structure. This neurotoxin causes cellular dysfunction and the death of dopaminergic neurons. To a degree, it replicates Parkinson’s in a laboratory setting.
The rodents’ motor behavior was assessed four weeks after this procedure.
Compared to controls, NAD treatment eased Parkinson’s motor symptoms in animals injected with the 6-OHDA neurotoxin. In addition, brain tissue analysis revealed 6-OHDA-induced dopaminergic neuronal loss was significantly reversed by NAD injection. This was found both in the striatum and in the substantia nigra, another key brain region involved in motor function that is also affected in Parkinson’s.
Scientists then used cell culture technology to test if administering NAD to cells before they were damaged by 6-OHDA could protect them from cellular structural and molecular damage — including oxidative stress and mitochondrial problems.
Results revealed that the almost 50% reduction in cell viability caused by 6-OHDA was markedly reduced if cells were treated beforehand with NAD. The neurotoxin also caused changes in cell morphology (the size, shape and structure of cells), increased oxidative stress levels, and impaired mitochondrial function. Importantly, these alterations were all reversed following NAD pre-treatment.
“These results add credence to the beneficial role of NAD against parkinsonian neurodegeneration in mouse models of PD [Parkinson’s disease], provide evidence for the potential of NAD for the prevention of PD [Parkinson’s disease], and suggest that NAD prevents pathological changes in PD via decreasing mitochondrial dysfunctions,” the team concluded.