Baicalein attenuates astroglial activation in the 1‐methyl‐4‐phenyl‐1,2,3,4‐tetrahydropyridine‐induced Parkinson's disease model by downregulating the activations of nuclear factor‐κB, ERK, and JNK

Abstract

In Parkinson's disease (PD), neuroinflammation plays a critical role in the neurodegenerative process. Furthermore, activated microglia and astrocytes, responsible for activated immune response in the central nervous system, are found in regions associated with dopaminergic neuronal death. The flavonoid baicalein is known to have antibacterial, antiviral, and antiinflammatory activities. In the present study, the neuroprotective effects of baicalein were examined in a murine 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP) model of PD. Low doses of baicalein improved motor ability and prevented dopaminergic neuron loss caused by MPTP. In addition, microglial and astrocyte activations were reduced in PD mice pretreated with baicalein. Further study of primary astrocytes revealed that baicalein suppressed the 1-methyl-4-phenylpyridine-induced nuclear translocation of nuclear factor-κB and reduced the activations of JNK and ERK, suggesting that the neuroprotective effects of baicalein in our PD model were due to attenuated astrocyte activation. The findings of this study indicate that baicalein could be useful for the treatment of PD and other neuroinflammation-related neurodegenerative diseases.

Absence of Glia Maturation Factor Protects Dopaminergic Neurons and Improves Motor Behavior in Mouse Model of Parkinsonism

“…Post-mortem analysis and in vivo imaging of PD patient brains showed activation of microglia, astrogliosis and infiltration of peripheral immune cells in the SN and STR (Hirsch et al, 1998; Ouchi et al, 2009; Tansey and Goldberg, 2010). These features were also observed in experimental rodents brain after MPTP treatment (Khan et al, 2013; Lee et al, 2014; Noelker et al, 2013). The glia maturation factor (GMF), discovered and characterized in our laboratory, is a conserved protein in mammalian brain/central nervous system (Lim et al, 1989; Lim et al, 1990; Zaheer et al, 2011a).…”

Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury

“…The current study investigated the mechanism underlying these effects by inducing a PD-like syndrome using rotenone, as evidenced by the diminished performance on the rotarod test and loss of dopaminergic neurons in the midbrain (Fig. 1), which was consistent with results of previous studies that used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to induce PD (Costa et al, 2013;Toy et al, 2013;Lee et al, 2014). An assessment of gait using catwalk analysis revealed that rotenone caused a shortening of print width and length, which is consistent with published reports of 6-OHDAinduced PD (Chuang et al, 2010), (Hsieh et al, 2011) and comparable to what is observed in PD patients who experience rigidity of the muscles that consequently limits movement.…”

Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model

“…Enhanced inflammatory response and oxidative stress caused by microglia activation may play a crucial role in PD by mediating dopaminergic cell death [30,48,49]. Transduced PEP-1-PON1 proteins inhibited MPP þ induced oxidative stress in SH-SY5Y cells which can lead to mitochondria dysfunction and intrinsic apoptotic signaling.…”