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Advanced Neurology Alzheimer’s and Parkinson’s disease rodent models

aggregation is a hallmark of AD, Aβ serves as a viable option predominantly used for PD research, whereas genetic
for modeling AD pathology. Mice injected with Aβ present models are favored for AD investigations. The most used
mitochondrial dysfunction, tau hyperphosphorylation, models for PD during this period, in descending order,
and cholinergic dysfunction, although the presence of were the MPTP-induced model, 6-OHDA-induced model,
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NFTs is not observed. Furthermore, these mice manifest and α-Syn-genetic-overexpression model. Conversely, for
cognitive, memory, and learning impairments. 119 AD research, the most used models, in descending order,
were APP/PS1 mice, 5×FAD mice, APP-based transgenic
4.2.3. Aluminum chloride (AlCl3) and D-gal mice, and 3×Tg mice. Notably, several new rodent
Aluminum is a metal commonly ingested through food and models for AD were reported among the selected studies,
water, owing to its widespread use in water purification, highlighting the ongoing necessity for robust models in
utensils, wrapping foils, food additives, and compounds this field. However, it is important to fully validate these
in medicines and cosmetics. However, excess aluminum models in future research to ensure their reliability and
intake can pose potential toxicity risks, especially to the relevance to the disease under investigation.
central nervous system. 120,121 Accumulation of aluminum Biomedical research employing animal models
in the brain precipitates mitochondrial dysfunction necessitates consideration of multiple factors. Animal
and aggressively elevates oxidative stress, particularly models, while valuable, inherently mimic only certain
observed in memory-related regions such as the cortex and aspects of human diseases, failing to cover the full complexity
hippocampus. Therefore, an AD model can be established observed in patients. Both AD and PD entail important
in rodents through intraperitoneal injection of 100 mg/kg neuronal, molecular, metabolic, and immunological
of body weight/day of AlCl over a period of approximately changes. These alterations collectively constitute a dynamic
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40 days. Another chemical used to induce an AD model pathophysiological process. Thus, the main limitation of
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is D-gal, a monosaccharide mainly found in dairy products.
Chronic subcutaneous administration of D-gal (usually animal models lies in their inability to fully replicate the
daily for about 10 weeks) exacerbates oxidative stress in multifaceted nature of human diseases. No single model
the hippocampus, leading to the generation of ROS and can encompass all the characteristics observed in patients.
neuroinflammation. Some studies describe combining the Therefore, the selection of the most suitable animal model
AlCl model with D-gal administration to induce an AD depends on the specific research questions being investigated
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model. This combination may be employed because D-gal, and the disease aspects deemed relevant to the study.
as a sugar, induces an insulin-resistance-like state, thus Consequently, the chosen model must effectively address
mimicking insulin resistance-associated AD states. 112 the research inquiries as comprehensively and efficiently
as possible. Researchers must carefully consider the
4.2.4. Scopolamine characteristics and limitations of each model when designing
Scopolamine, an alkaloid derived from Hyoscyamus their studies. This includes assessing which histopathological
niger, possesses potent anticholinergic properties aspects are mimicked, how the disease is induced or
and is commonly used to alleviate motion sickness. established, and which molecular and behavioral features
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However, given the critical role of central cholinergic are observed in a particular model. In addition, financial
neurotransmission in memory formation and processing, considerations, such as the costs associated with establishing
scopolamine can serve as a tool to induce cholinergic and maintaining animal colonies, cannot be ignored either.
dysfunction, thus creating a psychopharmacological 6. Conclusion
model of AD. As a competitive antagonist of muscarinic
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acetylcholine receptors, scopolamine is associated with In this review, we discuss the most used animal models
heightened acetylcholinesterase (AChE) activity, increased for PD and AD over the past 5 years. With numerous
ROS production, and promotion of Aβ deposition. In models available, each possesses distinct characteristics
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rodent models, scopolamine is typically administered and limitations. However, it is impossible to completely
intraperitoneally at a dose of approximately 2 mg/kg, as replicate human pathology in rodent models. Therefore, it is
it effectively crosses the blood–brain barrier, facilitating a fundamental to comprehensively understand the advantages
simple and easy procedure. 112 and disadvantages of each model. This review furnishes
essential information to aid researchers in selecting the most
5. Summary and future perspectives suitable model for their studies in the field.
In this article, we systematically reviewed studies Acknowledgments
employing rodent models of AD and PD over the past
5 years. Our analysis revealed that induced models are None.

Volume 3 Issue 3 (2024) 12 doi: 10.36922/an.2903