apelin-13-peptide and Parkinson-Disease--Secondary

The hippocampus is involved in learning and memory for novel information and implicated within the cognitive dysfunction in Parkinson's disease. Long-term potentiation (LTP), the most type of synaptic plasticity, is the base of learning and memory. We evaluated the consequences of apelin-13 on early long-term potentiation (E-LTP) in the Cornu Ammonis (CA1) area of the hippocampus and synaptic hippocampal protein expression of postsynaptic density protein 95 (PSD-95) and dopaminergic receptor (DR1) of the rat model of Parkinsonism. 6-hydroxydopamine (6-OHDA) was infused within the right substantia nigra. Intra-nigral transfusion of apelin-13 (1, 2, and 3 μg/rat) was performed one week after the 6-OHDA injection. Using hematoxylin and eosin staining, the pathological changes in the substantia nigra neurons were examined. In Vivo field excitatory postsynaptic potentials were recorded in the CA1 region one month after the apelin injection. The PSD-95 and DR1 protein levels were assessed by western blotting. The mRNA expression level of DR1 was also measured by real-time PCR. 6-OHDA meaningfully disrupted short-term memory and LTP, and altered the expression levels of the above-mentioned proteins in the hippocampus. The results suggest that apelin-13 (especially at 3 μg/rat) significantly ameliorates the E-LTP impairment and attenuates the changes in hippocampal synaptic proteins in 6-OHDA-treated rats.

Topics: Animals; Disks Large Homolog 4 Protein; Hippocampus; Intercellular Signaling Peptides and Proteins; Male; Neuronal Plasticity; Neurons; Oxidopamine; Parkinson Disease, Secondary; Rats; Rats, Wistar; Receptors, Dopamine D1; Substantia Nigra

The striatum plays a critical role in motor control and also learning and memory of motor skills. It has been reported that striatal synaptic components are significantly decreased in dopaminergic-denervated striatum. In this study the effects of apelin-13 were investigated on motor disorders and striatal synaptosomal expression of PSD-95, neurexin1, neuroligin, metabotropic glutamate receptor (mGlu R1) and dopaminergic receptors (DR1 and DR2) in rat parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was injected into the substantia nigra. Apelin-13 (1, 2 and 3 μg/rat) was administered into the substantia nigra one week after the 6-OHDA injection. Accelerating rotarod, beam-balance, beam-walking and bar tests were performed one month after the apelin injection. Immunohistochemistry staining of dopaminergic neurons was performed. The levels of synaptic proteins were determined by immunoblotting. 6-OHDA-treated animals showed a significant impairment in motor-skill tasks and a dramatically change in the expression levels of mentioned proteins. Apelin-13 (3 μg/rat) significantly attenuates the motor impairments and prevents the changes in striatal synaptic elements in 6-OHDA-treated animals. In addition, it could rescue the dopaminergic neurons of the substantia nigra. The data will potentially extend the possible benefic aspect of apelin in neurodegenerative disorders.

Topics: Animals; Corpus Striatum; Intercellular Signaling Peptides and Proteins; Male; Motor Disorders; Neuronal Plasticity; Oxidopamine; Parkinson Disease, Secondary; Rats; Rats, Wistar