| Parkinson’s disease (PD) is a progressive, neuro-degenerative disorder of the central nervous system, which usually occurs in the elderly. The main pathological feature is the degeneration of the dopaminergic neurons in the substantia nigra and corpus striatum, resulting in the lack of dopamine (DA) in the brain, which produces a series of pathophysiological changes. Although the etiology of PD is not completely understood, it is generally regarded as a multicenter, neurodegenerative disease that is associated with the gradual deterioration of a number of neurotransmitter systems. The clinical symptoms are resting tremor, bradykinesia, muscle rigidity, and postural balance disorders. Drug treatment is still the main therapy for Parkinson’s disease because of the high costs associated with surgical treatments. However, the existing drugs that are used to treat Parkinson’s disease only improve the symptoms to a limited extent, and they do not prevent the further degeneration of DA neurons. In addition, increasing the dosages of these drugs and their long-term use can produce serious side effects. In recent years, the medications used to treat Parkinson’s disease have been changed from direct supplementation of DA to multi-link treatment and focused on protecting the DA neurons. Basic fibroblast growth factor (bFGF) is one of the growth factors that produce a mitogenic effect both in vivo and in vitro. It interacts with the tyrosine kinase receptors on the surfaces of cells, and it has important roles in neuroprotection.This study takes the lesions source of PD-in neurons nutrition repair terms, to research the impact of bFGF on PD brain through the change of animal behavior, neurotransmitter content, and neuron number. The goal was to elucidate the possible mechanism of bFGF repairing neurons and affecting PD neurotransmitter by detecting a variety of relevant biochemical markers. Specifically, the research addressed the following three points:(1) The establishment of the cell model of Parkinson’s disease induced by neurotoxin6-hydroxydopamine (6-OHDA). At the cellular level, bFGF can improve the PC12cells’ survival rate, reduce6-OHDA-induced PC12cell apoptosis, promote cell-related monoamine neurotransmitters and their metabolites, and stimulate the expression of tyrosine hydroxylase (TH) in vitro. Also, bFGF can improve the levels of phosphorylated Akt and ERK proteins in cells and inhibit the expression of the endoplasmic reticulum stress protein (CHOP, GRP78, and CASPASE12). This suggests that bFGF may achieve a neuroprotective effect by activating the PI3K/Akt and ERK1/2pathways to inhibit the endoplasmic reticulum stress caused by6-OHDA oxidative damage and by reducing neuronal apoptosis.(2) The cerebral stereotaxic technique was used in this experiment, and6-OHDA was injected into the partial side of the rats to induce the PD model. Then, the model was verified by the behavioral changes that occurred after the intraperitoneal injection of apomorphine solution. By using bFGF in animals, we can effectively improve the animal model of Parkinson’s disease symptoms, including increasing the monoamine neurotransmitter content in the intracellular and extracellular striatum tissue in rats, which promotes the expression of TH in the substantia nigra and corpus striatum of the brain. In addition, bFGF can promote the scavenging of free radicals in the brains of the PD rats, raise the phosphorylation Akt and ERK levels in their damaged striata, and inhibit the expression of endoplasmic reticulum stress protein (CHOP, GRP78and CASPASE12) and a-Syn protein expression. All of these data suggest that bFGF may activate the PI3K/Akt and ERK1/2pathways, inhibit the endoplasmic reticulum stress and a-Syn protein levels caused by6-OHDA oxidative damage, improve the expression of TH, reduce DA neurons apoptosis, and then improve the synthesis of neurotransmitters. As a result, bFGF can improve the symptoms of PD and achieve neuroprotective effects in PD.(3)’H NMR-based metabolomic studies in PD rat striatum showed that the contents of lactic acid, gamma--aminobutyric acid, glutamic acid, creatine, glycine, and inositol were increased. However, the expressions of N-acetyl aspartic acid and taurine were decreased. After bFGF treatment, gamma-aminobutyric acid, N-acetyl aspartic acid, and taurine content increased significantly in the striatum of the PD rat brains; the contents of glutamic acid, inositol, and lactate were decreased. The results showed that bFGF can recover unbalanced amino acid neurotransmitters in the striatum, improving astrocyte proliferation, promoting astrocyte trophic factor secretion, exhibiting nutrition, and repairing the effects in the DA neurons.In summary, we researched the changes in the neurotransmitters in Parkinson’s disease before and after treatment with bFGF. We also researched the changes in the biochemical indices of endoplasmic reticulum stress and a-Syn protein expression providing a new mechanism for bFGF to improve the symptoms of PD. These findings provided experimental evidence for the design of a new type of PD therapy and the establishment of a treatment strategy for PD. In addition, our research marked the first time that the metabonomics method was used in the study of the PD model. In this study, we identified some small, metabolic-disorder, amino acid molecules in the PD brain from the systems biology level, which provided new ideas about the pathogenesis, development, and treatment strategies of... |
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