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In this study, we aimed to investigate the effects of carvacrol (CA), a widely used phytochemical having anti-oxidant and neuroprotective effects, on transient receptor potential (TRP) channels in an animal model of Parkinson's disease (PD). A total of 64 adult male Spraque-Dawley rats were divided into four groups: sham-operated, PD animal model (unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA), 6 µg/µl), PD + vehicle (dimethyl sulfoxide (DMSO)) treatment, and PD + CA treatment (10 mg/kg, every other day, for 14 days). Half of the brain samples of substantia nigra pars compacta (SNpc) and striatum (CPu) were collected for immunohistochemistry and the remaining half were used for molecular analyses. CA treatment significantly increased the density of dopaminergic neurons immunolabeled with tyrosine hydroxylase and transient receptor potential canonical 1 (TRPC1) channel in the SNpc of PD animals. In contrast, the density of astrocytes immunolabeled with glial fibrillary acetic acid and transient receptor potential ankyrin 1 (TRPA1) channel significantly decreased following CA treatment in the CPu of PD animals. RT-PCR and western blot analyses showed that 6-OHDA administration significantly reduced TRPA1 and TPRPC1 mRNA expression and protein levels in both SNpc and CPu. CA treatment significantly upregulated TRPA1 expression in PD group, while TRPC1 levels did not display an alteration. Based on this data it was concluded that CA treatment might protect the number of dopaminergic neurons by reducing the reactive astrogliosis and modulating the expression of TRP channels in both neurons and astrocytes in an animal model of PD. [ABSTRACT FROM AUTHOR]

AIM: Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Carvacrol (CA) modulates Transient Receptor Potential (TRP) cation channels. In our study, the effects of CA on TRPC1 in dopaminergic neurons and TRPA1 in astrocytes and the role of these channels in PD were investigated in the model of Parkinson's induced by 6-hydroxydopamine (6-OHDA). METHODS: Experiments were performed in 4 groups of male Sprague-Dawley rats. Groups; 1) Sham (Placebo Surgery), 2) 6-OHDA, 3) 6-OHDA+Vehicle (DMSO=Dimethyl sulfoxide), 4) 6-OHDA + CA (10 mg/kg). TRPC1 and TRPA1 immunoreactivity in brain tissue sections of 8 animals of each group was determined by immunohistochemical staining method. The SNpc and striatal areas of the brains of the other 8 animals in the groups were used for molecular studies. RESULTS: the immunohistochemical analysis; there was a decrease in the number of TRPC1(+) dopaminergic neurons due to the Parkinson. This decrease in cell number was also observed in the DMSO and CA groups. However, dopaminergic neurons in the preparations of the CA group had a healthier appearance due to the neuroprotective effect of CA, and their cell integrity was preserved compared to the cells in the DMSO group. CA had no significant effect on gene expression and protein levels of dopaminergic neuron TRPC1 channels. While the number of TRPA1(+) cells in astrocytes decreased in the CA treatment group compared to the control group, gene expression levels increased significantly. As in TRPC1(+) dopaminergic cells, it was observed that cellular integrity was preserved by CA in treatment group astrocytes. CONCLUSION: CA showed neuroprotective effect in the presented Parkinson animal model, TRPC1 is inhibited by CA in dopaminergic cells İn addition, CA activates TRPA1 channels, because of increased channel expression in astrocytes may be useful in neuron survival by triggering the neuromodulatory effects. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a late-onset neurodegenerative disorder with both familial and sporadic presentation. The main pathological characteristic of PD is the death of dopaminergic neurons in the substantia nigra (SN) pars compacta. PD is the second most common neurodegenerative disease worldwide, after Alzheimer’s disease. Recent studies have suggested increased levels of iron and iron-binding proteins in the brains of patients with PD. Divalent metal transporter 1 (DMT1) is one protein responsible for iron transport. Postmortem studies have shown an important increase in DMT1 levels in the SN of patients with PD. Our aim is to determine whether there is an association between DMT1 polymorphisms and PD. We analyzed two single nucleotide polymorphisms (1254T > C and IVS4 + 44C > A) in the DMT1 gene in patients with 97 Parkinson’s disease and in 100 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). No association was found between the IVS4 + 44C > A polymorphism and PD, but the TT genotype and T allele of the 1254T > C polymorphism in the DMT1 gene were associated with PD ( P = 0.002 and P = 0.012, respectively). In contrast to a previous study, our results suggest that the TT genotype and T allele of the 1254T > C polymorphism may be a risk factor for PD. [ABSTRACT FROM AUTHOR]