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Updated: Jul 5, 2025
Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
New insights in animal models of neurotoxicity-induced neurodegeneration
Coral Sanfeliu1, Clara Bartra1,2, Cristina Suñol1
1Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Abstract:
The high prevalence of neurodegenerative diseases is an unintended consequence of the high longevity of the population, together with the lack of effective preventive and therapeutic options. There is great pressure on preclinical research, and both old and new models of neurodegenerative diseases are required to increase the pipeline of new drugs for clinical testing. We review here the main models of neurotoxicity-based animal models leading to central neurodegeneration. Our main focus was on studying how changes in neurotransmission and neuroinflammation, mainly in rodent models, contribute to harmful processes linked to neurodegeneration. The majority of the models currently in use mimic Parkinson's disease (PD) and Alzheimer's disease (AD), which are the most common neurodegenerative conditions in older adults. AD is the most common age-related dementia, whereas PD is the most common movement disorder with also cases of dementia. Several natural toxins and xenobiotic agents induce dopaminergic neurodegeneration and can reproduce neuropathological traits of PD. The literature analysis of MPTP, 6-OH-dopamine, and rotenone models suggested the latter as a useful model when specific doses of rotenone were administrated systemically to C57BL/6 mice. Cholinergic neurodegeneration is mainly modelled with the toxin scopolamine, which is a useful rodent model for the screening of protective drugs against cognitive decline and AD. Several agents have been used to model neuroinflammation-based neurodegeneration and dementia in AD, including lipopolysaccharide (LPS), streptozotocin, and monomeric C-reactive protein. The bacterial agent LPS makes a useful rodent model for testing anti-inflammatory therapies to halt the development and severity of AD. However, neurotoxin models might be more useful than genetic models for drug discovery in PD but that is not the case in AD where they cannot beat the new developments in transgenic mouse models. Overall, we should work using all available models, either in vivo, in vitro, or in silico, considering the seriousness of the moment and urgency of developing effective drugs.
Insights
Developing effective treatments for neurodegenerative diseases like Parkinson's (PD) and Alzheimer's (AD) requires robust preclinical models. This review highlights neurotoxicity-based rodent models for studying neurotransmission and neuroinflammation in PD and AD drug discovery.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Neurodegenerative diseases (NDs) are a growing concern due to increased longevity and limited therapeutic options.
- Preclinical research urgently needs diverse animal models to accelerate drug development pipelines.
- Existing models primarily focus on Parkinson's disease (PD) and Alzheimer's disease (AD).
Purpose of the Study:
- To review neurotoxicity-based animal models for central neurodegeneration.
- To analyze the contribution of neurotransmission and neuroinflammation to neurodegeneration in rodent models.
- To evaluate the utility of these models for drug discovery in PD and AD.
Main Methods:
- Literature analysis of neurotoxin-induced neurodegeneration models.
- Focus on rodent models mimicking PD and AD.
- Examination of models for neurotransmission (e.g., MPTP, 6-OH-dopamine, rotenone, scopolamine) and neuroinflammation (e.g., LPS, streptozotocin).
Main Results:
- Rotenone and MPTP are useful for modeling PD-related dopaminergic neurodegeneration.
- Scopolamine effectively models cholinergic neurodegeneration for AD drug screening.
- LPS is a valuable model for testing anti-inflammatory therapies in AD.
- Neurotoxin models may be superior to genetic models for PD drug discovery, while transgenic models are advancing for AD.
Conclusions:
- Neurotoxicity-based animal models are crucial for understanding and treating neurodegenerative diseases.
- A combination of *in vivo*, *in vitro*, and *in silico* approaches is necessary for effective drug development.
- Continued research and model development are vital given the urgency of addressing neurodegenerative conditions.
