Linalol Protects Against Dopaminergic Neurons Loss in the 6‐OHDA Model of Parkinson's Disease

(−)‐Linalol (LIN), a monoterpene alcohol, is a component of many natural aromatic plants. LIN has been found to have biological activities, including anticonvulsant, anti‐depressant, anti‐inflammatory and anti‐oxidant effects in the Central Nervous System (CNS). Considering the importance of inflammation and oxidative stress in Parkinson's disease (PD), LIN neuroprotective effects were evaluated in a model of PD. Male Wistar rats (250–270 g) were kept at 24 ± 2 °C, in a 12 h dark/12 h light cycle, with water and food ad libitum. The study was submitted to the Ethical Committee for Animal Experimentation of the Federal University of Ceará (Brazil) and was approved under the number 64/2015. The rats were divided into 4 groups: sham‐operated (SO), untreated 6‐hydroxydopamine (6‐OHDA) and 6‐OHDA treated with LIN (50 and 100 mg/kg, p.o.). The 6‐OHDA was injected into the right striata and LIN treatments started 24 h later for 2 weeks. Afterwards, the animals were subjected to the apomorphine‐induced rotation and open field tests and euthanized for striatal measurements of dopamine (DA) and DOPAC by HPLC, and immunohistochemistry assays for tyrosine hydroxylase (TH) and dopamine transporter (DAT). Statistical analysis were performed by One‐way Anova, followed by Tukey post hoc test, used for multiple comparisons. The photomicrographs' data were quantified in relative optical density by the Image J software (NIH, USA). Differences were considered significant at p < 0.05. The results showed that the 6‐OHDA group treated with LIN (50 and 100 mg/kg, p.o.) reduced the apomorphine‐induced behavioral alterations by 48 and 44%, respectively, p<0.0001 (Figure 1A). In the open‐field test, only the treated 6‐OHDA with LIN50 showed a significant increase (30.4 ± 2.072) in the locomotor activity, compared with the untreated 6‐OHDA, p<0.0001 (Figure 1B). In addition, the treatment with LIN with both doses caused significant increases (LIN50: 17.0 ± 2.212; LIN100: 14.8 ± 0.637) in the rearing behavior, compared with the untreated 6‐OHDA, p<0.0001 (Figure 1C). Furthermore, the untreated 6‐OHDA showed around a 75% decrease of striatal DA contents, relatively to the ipsilateral side of the SO group and to its own contralateral side. Smaller decreases in DA contents were presented in the 6‐OHDA groups, after treatments with LIN (50 and 100 mg/kg), compared with the ipsilateral side of the SO group or to the contralateral side of these two groups, Figure 2A. As far as the DOPAC levels are concerned, the untreated 6‐OHDA showed around a 75% decrease, relatively to the right side of the SO group as well as its own contralateral side. The treated 6‐OHDA presented smaller decreases after LIN treatments comparatively to the ipsilateral side of the untreated 6‐OHDA and to their own contralateral sides (Figure 2B). The immunohistochemical data for DAT showed a 31.7% decrease in the immunoreactivity on the striatal right of the untreated 6‐OHDA related to the SO group. On the other hand, no significant change in DAT (2.4%) immunostaining was observed in the 6‐OHDA group, after the treatment with LIN (50 mg/kg). In immunohistochemistry for TH, observed a decrease in immunoreactivity in 46% in the right striatum of the untreated 6‐OHDA. This reduction was blocked (95%) in the 6‐OHDA group after treatment with LIN (50 mg/kg), Figure 3. Thus, we showed that behavioral and neurochemical alterations in animals induced by 6‐OHDA were partly reversed by LIN, presenting a potential neuroprotective action of (−)‐linalol in PD. Support or Funding Information Coordenação de Aperfeiçoamento de Pessoal de Nível Superior This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .