Antiparkinsonian-like effects of CPL500036, a novel selective inhibitor of phosphodiesterase 10A, in the unilateral rat model of Parkinson's disease.

Phosphodiesterase 10A (PDE10A), the enzyme which catalyzes hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), is located almost exclusively in striatal γ-amino-butyric acid (GABA)ergic medium spiny neurons (MSNs). Since dopaminergic deficiency in Parkinson's disease (PD) leads to functional imbalance of striatal direct and indirect output pathways formed by MSNs, PDE10A seems to be of special interest as a potential therapeutic target in PD. The aim of the present study was to examine the influence of 7-{5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl}-2-phenylimidazo[1,2-a]pyrimidine (CPL500036), a novel selective inhibitor of PDE10A, on sensorimotor deficits and therapeutic effects of L-3,4-dihydroxyphenylalanine (L-DOPA) in hemiparkinsonian rats.

Inhibition of Excessive Glutamatergic Transmission in the Ventral Thalamic Nuclei by a Selective Adenosine A1 Receptor Agonist, 5'-Chloro-5'-Deoxy-(±)-ENBA Underlies its Tremorolytic Effect in the Harmaline-Induced Model of Essential Tremor.

The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-N6-(±)-(endo-norborn-2-yl)adenosine (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor (A1) agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures.

Adaptation within mitochondrial oxidative phosphorylation supercomplexes and membrane viscosity during degeneration of dopaminergic neurons in an animal model of early Parkinson's disease.

In Parkinson's disease (PD) motor symptoms are not observed until loss of 70% of dopaminergic neurons in substantia nigra (SN), preventing early diagnosis. Mitochondrial dysfunction was indicated in neuropathological process already at early PD stages. Aging and oxidative stress, the main factors in PD pathogenesis, cause membrane stiffening, which could influence functioning of membrane-bound oxidative phosphorylation (OxPhos) complexes (Cxs) in mitochondria.

Adaptive down-regulation of the serotonin transporter in the 6-hydroxydopamine-induced rat model of preclinical stages of Parkinson's disease and after chronic pramipexole treatment.

Our recent study has indicated that a moderate lesion induced by bilateral 6-hydroxydopamine (6-OHDA) injections into the ventrolateral region of the caudate-putamen (CP) in rats, modeling preclinical stages of Parkinson's disease, induces a "depressive-like" behavior which is reversed by chronic treatment with pramipexole (PRA). The aim of the present study was to examine the influence of the above lesion and chronic PRA treatment on binding to the serotonin transporter (SERT) in different brain regions. As before, 6-OHDA (15 μg/2.

Alterations of BDNF and trkB mRNA expression in the 6-hydroxydopamine-induced model of preclinical stages of Parkinson's disease: an influence of chronic pramipexole in rats.

Our recent study has indicated that a moderate lesion of the mesostriatal and mesolimbic pathways in rats, modelling preclinical stages of Parkinson's disease, induces a depressive-like behaviour which is reversed by chronic treatment with pramipexole. The purpose of the present study was to examine the role of brain derived neurotrophic factor (BDNF) signalling in the aforementioned model of depression. Therefore, we investigated the influence of 6-hydoxydopamine (6-OHDA) administration into the ventral region of the caudate-putamen on mRNA levels of BDNF and tropomyosin-related kinase B (trkB) receptor.