| dc.description.abstract | The progressive decline of dopaminergic neurons in Parkinson's disease (PD) has been linked to an imbalance in energy and the failure of mitochondrial function. AMP-activated protein kinase (AMPK), the major intracellular energy sensor, regulates energy balance, and damage to nigral dopaminergic neurons induced by 6-hydroxydopamine (6-OHDA) is exacerbated in the absence of AMPK activity. This study aimed to examine the potential therapeutic advantages of AdipoRon, an AMPK activator, on motor function and mitochondrial homeostasis in a 6-OHDA-induced PD model.
Materials and Methods: Seventy-two male Wistar rats were subjected to unilateral injection of 6-OHDA (10 μg) into the left medial forebrain bundle at two points, and after 7 days, they were treated with intranasal AdipoRon (0.1, 1, and 10 µg/rat) or Levodopa (10 mg/kg, p.o.) for 21 successive days. Following the last treatment day, motor function was evaluated through the Murprogo’s test, Bar test, Beam walking test, and apomorphine-induced rotation test. After euthanasia, in the half of the animals, the left substantia nigra (SN) was separated for evaluation of ATP, mitochondrial membrane potential (MMP), and protein expressions of AMPK, phospho-AMPK, and mitochondrial dynamics markers (Mfn-2 and Drp-1). Moreover, in other half of the animals, the number of tyrosine hydroxylase-positive (TH+) cells was quantified in the left SN by immunohistochemistry method.
Results: Intranasal AdipoRon effectively reversed muscle rigidity, akinesia, bradykinesia, and rotation caused by 6-OHDA. Moreover, AdipoRon activated the AMPK pathway, mitigated mitochondrial dysfunction, and improved mitochondrial dynamics in the SN. Furthermore, AdipoRon increased the number of TH+ cells in the substantia nigra of PD animals. | en_US |
