Irisin reduces neurodegeneration and neuroinflammation in the 6-hydroxydopamine rat model of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide. With the number of cases expected to continue rising, there is an urgent need for new treatments. Irisin, a peptide released by skeletal muscle during exercise, has been proposed as a key mediator of the beneficial effects of physical activity on the brain. However, its potential neuroprotective role in PD remains unclear. Here, we established a PD model by injecting 6-hydroxydopamine into the right striatum of rats, followed by irisin administration into both cerebral lateral ventricles. Motor behavior was assessed, and brain tissue was collected for analysis of nigral dopaminergic neuron numbers in the substantia nigra pars compacta (SNc), axonal terminal density in the striatum (CPu), and glial cell reactivity. Our findings showed that irisin-treated PD animals exhibited a higher number of dopaminergic neurons (n=6/group; +11,8 ± 3,6%; p=0.013), increased terminal density in the striatum (n=6/group; +18,8 ± 5,1%; p<0.001), and reduced the number of asymmetrical rotations when compared to untreated rats (n=6/group; -73,6 ± 32,4%; p<0.001). Additionally, irisin reduced microglia (n=6/group; SNc: -27.8 ± 4.5%; p=0.030; CPu: -25.1±2.8%; p=0.019) and astrocytes (n=6/group; SNc: -30.9 ± 5.3%; p=0.013; CPu: -55.0±7.5%; p<0.001) density and alleviated morphological alterations (n=30 cells/group; increased number of branches and endpoints of glia cells; p<0.01 in all cases) indicating an anti-inflammatory effect. These results suggest that irisin exerts neuroprotective and anti-inflammatory effects in the 6-hydroxydopamine rat model of PD, highlighting its potential as a promising tool in the management of PD. • Irisin, an exercise-induced myokine, is neuroprotective in a parkinsonian rat model • Irisin alleviated motor impairment in the 6-hydroxy-dopamine Parkinson rat model • Microglial/astrocytic morphological changes are attenuated by intracerebral irisin