Geraniol ameliorates the motor behavior and neurotrophic factors inadequacy in MPTP-induced mice model of Parkinson's disease

Abstract

Many experiments affirm the notion that augmentation of neurotrophic factors (NTFs) activity, especially brain-derived neurotrophic factors and glial cell-derived neurotrophic factors, could prevent or halt the progress of neurodegeneration in Parkinson's disease (PD). In this study, we investigated the therapeutic accomplishment of geraniol (GE 100 mg/kg) on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mice model of PD. Current investigation proved that pretreatment with GE ameliorates the MPTP-induced alterations in behavioral, biochemical, immunohistochemical, and immunoblotting manifestations in mice. Systematically, the loss of dopaminergic neurons and reduced NTFs mRNA expressions induced by MPTP was ameliorated to a significant extent by pretreatment with GE. We found that GE confers a potent neuroprotective agent against MPTP-induced dopaminergic denervation and may become a potential therapeutic agent for PD and/or its progression.

Fig. 1

Rotarod performance after the acute regimen of GE and MPTP: pretreatment with GE improved MPTP-induced motor deficits. Mice were tested for motor function using the rotarod (motor function) test in different rpm (5, 10, 15, and 20 rpm). Values are given as mean ± SD for six mice in each group. a P < 0.05 compared to the control, b P < 0.05 compared to the MPTP control

Fig. 2

Drag test performance after the acute regimen of GE and MPTP: Pretreated with GE to MPTP group a profound improvement in sensory motor performance. Values are given as mean ± SD for six mice in each group. a P < 0.05 compared to the control, b P < 0.05 compared to the MPTP control

Fig. 3

Comparison of behavioral output between control and MPTP-treated mice. The footprint patterns were calculated from the stride length, mid digit toe of the first step, to the heel of the second step. The GE pretreatment improves the stride length after MPTP treatment. Values are given as mean ± SD for six mice in each group. a P < 0.05 compared to the control, b P < 0.05 compared to the MPTP control

Fig. 4

a Effect of GE on TH expression in SN. Representative microphotographs of the expression of TH was almost negligible in MPTP group as compared to control group, while the MPTP group treated with GE has shown a moderate staining of TH. However, the GE control group has shown no discernible change in TH staining as compared to control group. Original magnifications at ×4 and ×40. b Quantification of TH-IR was performed by counting the number of TH-IR neurons in SN. The mean value for TH-IR was determined for each group and was expressed as a percentage of that matched control mice. Values are expressed as mean ± SD of three mice per group. a P < 0.05, compared with the control. b P < 0.05, compared with the MPTP control group

Fig. 5

a BDNF and GDNF mRNA expression level changes in ST of control and experimental mice, and β-actin and GAPDH mRNA were used as housekeeping gene for the normalization of mRNA expressions. b Quantification graphs values are expressed as mean ± SD of three mice per group. a P < 0.05, compared with the control. b P < 0.05, compared with the MPTP control group

Fig. 6

a Western blot analysis of BDNF and GDNF expression levels in ST. Western blot was performed to study the protein expression levels of BDNF and GDNF in the striatal tissue after GE treated and GE non-treated mice. b Bar graph shows the comparison among the group, and density was quantified by scanning densitometry. Values are expressed as mean ± SD of three mice per group. a P < 0.05, compared with the control. b P < 0.05, compared with the MPTP control group

Fig. 7

a Western blot analysis of TH, DAT, and VMAT2 in ST of control and experimental mice. b The band density was quantified by scanning densitometry. Bar graph shows the comparison among groups. Values are expressed as mean ± SD of three mice per group. a P < 0.05, compared with the control. b P < 0.05, compared with the MPTP control group