Time-course behavioral features are correlated with Parkinson's disease‑associated pathology in a 6-hydroxydopamine hemiparkinsonian rat model

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. For decades, the unilateral 6-hydroxydopamine (6-OHDA) rat model has been employed to investigate the pathogenesis and therapy of PD. However, the behavior and associated pathological features of the model long term have not previously been described dynamically. In the present study, the unilateral model was established by 6-OHDA injection in the striatum. The PD rat model was determined 2 weeks following surgery, according to the apomorphine (APO)-induced rotations, cylinder, rotarod and open field tests. TH-positive neurons and fibers in the substantia nigra pars compacta (SNpc) and striatum, respectively, and glial activation in the SNpc, determined by glial fibrillary acidic protein (GFAP) expression for astrocytes and CD11b (Mac1) expression for microglia, were detected by immunohistological staining. Correlation analysis was performed to understand the association between PD-associated behavior and pathology. The behavioral impairment progressively deteriorated during the process of experiment. In addition, the decrease in TH-positive neurons was associated with an increase in GFAP- and Mac1-positive cells in the SNpc. Linear regression analysis indicated the association between behavioral and pathological changes. The results of the present study indicate that the APO-induced rotation, cylinder and rotarod tests are all sensitive and reliable strategies to predict the loss of TH+ neurons. These results provide a potential intervention time-point and a comprehensive evaluation index system for assessment of PD therapeutic strategies using the hemiparkinsonian rat.

Epothilone B Benefits Nigral Dopaminergic Neurons by Attenuating Microglia Activation in the 6-Hydroxydopamine Lesion Mouse Model of Parkinson’s Disease

“…We found that 6-OHDA treatment induced behavioral deficits in mice, such as a reduction in spontaneous motor behavior and motor incoordination, and these behavioral alterations were consistent with previous reports (Su et al, 2018 ). Behavioral impairments observed in the 6-OHDA-induced animal model of PD correlated with nigrostriatal neurodegeneration and depletion of DA and metabolites in the striatum.…”

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

“…In the pathogenesis, astrocytes are critical in initiating and perpetuating inflammatory process associated with PD. PD significantly increases the expression of GFAP as shown in primary cultured astrocytes (Yu et al, 2018) and in the substantia nigra pars compacta of rats (Su et al, 2018). In lipopolyscharride-evoked PD model, impairment of motor function and memory is accompanied with increased GFAP expression as well as enhanced expressions of α-synuclein, amyloid-β and p-Tau and reduced tyrosine hydroxylase (Zhang & Xu, 2018).…”

Comparison between Tail Suspension Swing Test and Standard Rotation Test in Revealing Early Motor Behavioral Changes and Neurodegeneration in 6-OHDA Hemiparkinsonian Rats

“…Indeed, it is common to wait three weeks after surgery for a stable nigrostriatal lesion development before using the lesioned animals for further analyses [8,[34][35][36][37]. The most prominent deficits reported for the 6-OHDA-injected models are asymmetries in sensorimotor reactivity starting from 6 weeks [8], posture over 19 weeks [35], impairments of motor coordination and balance skills starting from 2 weeks [10] after lesion. In a recent study, combining PET imaging and Catwalk gait analysis 4 weeks after 6-OHDA lesion in the MFB, it was shown that altered brain metabolism and gait abnormalities correlate with DAergic lesion severity in the rat, indicating that striatal DA depletion, focal changes of glucose metabolism, and motor impairments are strongly linked [38].…”

“…Several animal models have been employed in experimental studies concerning the pathogenetic mechanism of PD and therapeutic strategies [5]. The classical unilateral 6-hydroxydopamine (6-OHDA) model, showing PD-associated pathological and behavioral features, is considered one of the most useful tools in PD research [6][7][8][9][10]. Over the years, to lesion the mesencephalic dopamine (DA) neurons and reproduce, to some degree, PD motor impairments, different concentrations of 6-OHDA have been infused either into the SNc, medial forebrain bundle (MFB), or the ST, leading to partial or complete neurodegeneration [7,8,[10][11][12][13].…”

“…Most of the preclinical experiments have been focused on late-phase, chronic, fully DA-depleted states and it has been shown that behavioral motor biases are associated with a complete loss of the nigrostriatal pathway [6,8,10,12,[14][15][16]18]. Indeed, only a few studies have focused specifically on the early-phase behavioral responses after the 6-OHDA lesion in the ST [7,10,20,21], MFB [7,13,22], and SNc [23,24]. It was reported that the ST lesion induces spontaneous motor impairments which are observed as early as the first day after lesion [20].…”