Abstract
This study investigated the effects of the Cong Rong Shu Jing (CRSJ) compound on endoplasmic reticulum stress in a rat model of Parkinson's disease (PD). A total of 40 rats were subcutaneously injected with rotenone-sunflower oil emulsion into the back of the neck to establish a rat model of PD. These PD rats were randomly divided into low-, medium-, and high-dose groups (intragastric administration of 0.5, 1, and 2 g/kg CRSJ, respectively) and a model group (intragastric administration of the solvent; 10 rats per group). Furthermore, 10 rats each were attributed to the control and vehicle groups (both received intragastric administration of the CRSJ solvent, and the vehicle group were injected additionally with sunflower oil alone). A traction test was conducted two times, after the PD model establishment and after 14 days of CRSJ gavage. The numbers of tyrosine hydroxylase- (TH-) positive cells and the dopamine levels in the substantia nigra were assessed using immunohistochemistry and high-performance liquid chromatography, respectively. Western blotting detected the expression levels of α-synuclein, endoplasmic reticulum stress pathways-related proteins, cerebral dopamine neurotrophic factor (CDNF), mesencephalic astrocyte-derived neurotrophic factor (MANF), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins. Compared with the model group, the number of TH-positive cells in the substantia nigra was increased in the CRSJ groups. The expression levels of α-synuclein and the endoplasmic reticulum stress pathways-associated proteins glucose regulatory protein 78, inositol-requiring enzyme 1, apoptosis signal-regulating kinase 1, phosphorylated c-Jun N-terminal kinase, and caspase-12 were reduced. However, CRSJ administration elevated the expression levels of the neurotrophic factors CDNF and MANF, as well as those of p-PI3K and p-AKT. The CRSJ compound can relieve endoplasmic reticulum stress in PD rats and exerts protective effects in this animal model. These effects may be related to increased expression of neurotrophic factors and activation of the PI3K/AKT pathway.
Highlights
Typical pathological manifestations of Parkinson’s disease (PD) are the degeneration and loss of neurons in the dense part of the substantia nigra, as well as the formation of Lewy bodies in the residual neurons
Lewy bodies are mainly composed of a large number of un- or misfolded α-synuclein proteins, and their abnormal aggregation or precipitation can cause endoplasmic reticulum stress (ERS), which induces the degeneration of dopaminergic neurons [1]
Healthy rats have climbing abilities, which require proper grip strength and movement coordination. e traction test is a common observation model in Parkinson’s disease to detect behavioral deficits in limb movement and coordination of rats [11], and we used it to detect the influence of Cong Rong Shu Jing (CRSJ) on the movement coordination in PD rats. e higher the score in the traction test, the longer the rats were able to hang from the wire, the stronger the grip of the rats
Summary
Typical pathological manifestations of Parkinson’s disease (PD) are the degeneration and loss of neurons in the dense part of the substantia nigra, as well as the formation of Lewy bodies in the residual neurons. Lewy bodies are mainly composed of a large number of un- or misfolded α-synuclein proteins, and their abnormal aggregation or precipitation can cause endoplasmic reticulum stress (ERS), which induces the degeneration of dopaminergic neurons [1]. Glucose regulatory protein 78 (GRP78) is a molecular chaperone of the endoplasmic reticulum. It binds to membrane proteins of the endoplasmic reticulum, such as inositol-requiring enzyme 1 (IRE1α), preventing ERS. When abnormal proteins such as α-synuclein accumulate intracellularly, they can cause the disintegration of transmembrane proteins and initiate ERS. ERS facilitates the correct folding and translocation of α-synuclein and
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