The generation mechanisms of gait impairment in Parkinson's disease and corresponding animal models

Parkinson's disease (PD) is a common neurodegenerative disease, affecting one in every 100 persons above the age of 65 years. And common symptoms of PD include resting tremor, bradykinesia, rigidity, postural instability, and gait disturbance. Patients with gait disorder always reduce gait speed and step length with increased axial rigidity and impaired rhythmicity. Gait disorder is a common disabling symptom in patients with Parkinson's disease, and this symptom worsens with the progression of the disease, which seriously affects the patient's athletic independence and quality of life. The causes of PD are complex and not fully understood, and may be related to the interaction of factors such as aging, genetics and environmental and behavioral habits. The ability to move is critical to human and animal survival, and well-adapted, coordinated motor output depends on the neural circuits of the brain which plan, select, and generate motor commands. Multisensory information, such as somatosensory, visual and vestibular sensory, is integrated in various areas of the brain, resulting in well-adapted and coordinated gait and posture control of human and animals for the environment change. Instructions for precise motor and postural control are generated and issued in the motor cortex, and are used to plan and generate motor processes. Basal ganglia are involved in fine motor control neural networks. Brainstem regions involved in motor control (mainly mesencephalic locomotor region, MLR) send motor commands directly to the spinal cord and are associated with initiation of movement, movement speed regulation, movement stopping, and steering regulation. Studies of neural connectivity have provided information about the mechanisms of gait impairment. It is well known that the death of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the presence of intraneuronal proteinacious cytoplasmic inclusions, termed "Lewy bodies" (LBs) are the pathological hallmark of PD. Deficiency of SNc neurons leads to striatal dopamine deficiency, which is the cause of the main symptoms of PD. However, the neural mechanism of Parkinson's disease is not fully understood. In this case, the construction of animal models of Parkinson's disease facilitates the study of a more complete mechanism of gait network damage and can address unresolved questions from clinical research. PD models can be divided into two models: Neurotoxin models and genetic models. In recent years, researchers have also attempted to develop a combined neurotoxin and genetic modeling approach. When determining the best animal model to study gait disorders in PD, it is important to consider the similarity of the symptoms of motor deficits produced by the modeling to those of human gait disorders. Among neurotoxins to produce PD models, 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) are widely used. Currently, PD is mainly treated by medications and surgery, which can reduce motor symptoms and improve the quality of life of patients, but still cannot completely cure PD. This review discusses the research progress in rodent models of Parkinson's disease, as well as the study of gait disorders and neural mechanisms of Parkinson's disease, in order to provide diagnostic and therapeutic ideas for the treatment of Parkinson's disease in humans.