Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson's disease model rats

Abstract

The present study showed that the latency of rats moving on a vertical grid was significantly prolonged, and the number of rats sliding down from the declined plane was increased remarkably, in rotenone-induced Parkinson's disease model rats compared with control rats. The moving latency recovered to normal levels, but the number of slides was significantly increased at 28 days after model establishment. The slope test is a meaningful approach to evaluate the symptoms of Parkinson's disease model rats treated with rotenone. In addition, loss of substantia nigral dopaminergic neurons in model rats was observed at 1 day after the model was established, and continued gradually at 14 and 28 days. The expression of tyrosine hydroxylase-positive cells was significantly increased in gastrodin-treated rats at 14 days. Significant numbers of activated microglia cells were observed in model rats at 14 and 28 days; treatment of rats with Madopar at 28 days suppressed microglial activation. Treatment of rats with gastrodin or Madopar at 28 days significantly reduced interleukin-1β expression. The loss of substantia nigral dopaminergic neurons paralleled the microglial activation in Parkinson's disease model rats treated with rotenone. The inflammatory factors tumor necrosis factor-α and interleukin-1β are involved in the substantia nigral damage. Gastrodin could protect dopaminergic neurons via inhibition of interleukin-1β expression and neuroinflammation in the substantia nigra.

Keywords: Parkinson's disease; dopamine; gastrodin; interleukin-1β; microglia cells; neuroinflammation; rotenone.

Figure 1

Tyrosine hydroxylase (TH) expression in the substantia nigra of rats (immunohistochemical staining, light microscope, scale bars: 500 μm). A large number of TH-positive cells with deeply colored cell bodies and abundant processes were observed in the substantia nigra of normal rats (A). Compared with normal rats (A), the numbers of TH-positive cells and processes in model rats at 4 days (B) were clearly decreased, and lighter colored cell bodies were seen. The loss of TH-positive cells was aggravated in model rats at 14 days (C) and 28 days (D). Gastrodin at 14 days increased the numbers of TH-positive cells and processes (E) compared with the model group at 14 days (C). The numbers of TH-positive cells and processes of Madopar-treated rats also tended towards a decrease at 14 days (F).

Figure 2

Complement receptor (OX₄₂) staining in the midbrains of rats (immunohistochemical staining, light microscope, scale bars: 50 μm). Resting microglia had branches in the substantia nigra of normal controls that stained for OX₄₂ (A). Microglia cells showed an amoeba-like morphology in the model at 4 days (B), 14 days (C) and 28 days (D). Microglial activation was reduced in gastrodin-(E) and Madopar-treated rats (F). Arrows represent OX₄₂ positive expression.

Figure 3

Tumor necrosis factor-α staining in the midbrains of rats (immunohistochemical staining, light microscope, scale bars: 100 μm). Many dark brown-colored cells can be observed in the control rats (A). The number of positive cells was reduced in the model rats at 4 days (B) and 14 days (C). This was also the case in the gastrodin (D) and Madopar (E) groups at 14 days. The number of positive cells in the Madopar group at 28 days (F) was greater than that at 14 days (E).

Figure 4

Interleukin-1β staining in the midbrains of rats (immunohistochemical staining, light microscopy; scale bars in A–E: 100 μm; scale bars in A’–E’: 500 μm). (A, A’) Normal group; (B, B’): Model group at 14 days; (C, C’): Model group at 28 days; (D, D’): Gastrodin group at 28 days; (E, E’): Madopar group at 28 days. Dark brown-colored cells were observed in the control (A), and the number of these was increased in the model at 14 days (B) and 28 days (C). The number of positive cells was reduced in the gastrodin (D) and Madopar groups at 28 days (E).