Differential confounds of identification methods in Parkinson's disease models: neuroinflammatory aggravation by toe-clipping versus sensorimotor disruption by ear-tagging.
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引用次数: 0
Abstract
Background: Toe-clipping and ear-tagging are standard rodent identification methods. Their potential to confound outcomes in Parkinson's disease (PD) research remains poorly characterized.
New method: We evaluated the methodological impacts of these procedures in a C57BL/6 male mouse PD model using behavioral assays and neuropathological analyses.
Results: Toe-clipping triggered sustained neuroinflammation, with 5-toe clipped mice showing elevated Interleukin (IL)-1β compared to ear-tagged (mean difference = 0.3647, 95% CI: 0.1203-0.6090, P = 0.0025) and 2-toe clipped mice (mean difference = 0.2333, 95% CI: 0.00036-0.4663, P = 0.0496) in non-PD conditions. In PD conditions, 5-toe clipped mice exhibited elevated IL-1β compared to non-PD 5-toe clipped mice (mean difference = 0.3967, 95% CI: 0.1123-0.6810, P = 0.0016). Toe-clipping exacerbated motor deficits, with significant grip strength impairments in 5-toe versus control mice (mean difference = 1.513, 95% CI: 0.01114-3.016, P = 0.0479) and in PD-5-toe versus PD-control mice (mean difference = 2.542, 95% CI: 1.132-3.951, P = 0.0003). In contrast, ear-tagging selectively impaired pole test performance, with ear-tagged mice showing prolonged head-turning times versus controls (mean difference = 1.232, 95% CI: 0.3723-2.091, P = 0.0035) and 2-toe mice (mean difference = 1.438, 95% CI: 0.5789-2.298, P = 0.0008), effects maintained after PD modeling (PD-ear-tagged vs PD-control: mean difference = 1.367, 95% CI: 0.6123-2.121, P = 0.0003). Swimming speed did not differ between groups (P = 0.9891).
Comparison with existing methods: This study demonstrates that routine identification methods significantly influence PD research outcomes. The induced confounds-chronic neuroinflammation from toe-clipping and sensorimotor disruption from ear-tagging-can mimic or mask PD pathology, threatening data validity.
Conclusion: Identification methods must be documented as critical methodological variables. Adoption of non-invasive alternatives is imperative for rigor and reproducibility in neurodegenerative research.
期刊介绍：
The Journal of Neuroscience Methods publishes papers that describe new methods that are specifically for neuroscience research conducted in invertebrates, vertebrates or in man. Major methodological improvements or important refinements of established neuroscience methods are also considered for publication. The Journal''s Scope includes all aspects of contemporary neuroscience research, including anatomical, behavioural, biochemical, cellular, computational, molecular, invasive and non-invasive imaging, optogenetic, and physiological research investigations.
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