Background: Parkinson’s disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. Methods: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. Results: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. Conclusions: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH), Brain-derived neurotrophic factor (BDNF), bone marrow tyrosine kinase in chromosome X (BMX) protein expression level without affecting dopaminergic (DA) neuron loss in this PD rat model.

Background Much recent research effort in traumatic brain injury (TBI) has been devoted to the discovery of a reliable biomarker correlating with severity of injury. Currently, no consensus has been reached regarding a representative marker for traumatic brain injury. In this study, we explored the potential of epithelial/endothelial tyrosine kinase (Etk) as a novel marker for TBI. Methodology/Principal Findings TBI was induced in Sprague Dawley (SD) rats by controlled cortical impact. Brain tissue samples were analyzed by Western blot, Q-PCR, and immunofluorescence staining using various markers including glial fibrillary acidic protein, and epithelial/endothelial tyrosine kinase (Etk). Results show increased Etk expression with increased number and severity of impacts. Expression increased 2.36 to 7-fold relative to trauma severity. Significant upregulation of Etk appeared at 1 hour after injury. The expression level of Etk was inversely correlated with distance from injury site. Etk and trauma/inflammation related markers increased post-TBI, while other tyrosine kinases did not. Conclusion/Significance The observed correlation between Etk level and the number of impacts, the severity of impact, and the time course after impact, as well as its inverse correlation with distance away from injury site, support the potential of Etk as a possible indicator of trauma severity.

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In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.

The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.