Mice in translational neuroscience: What R we doing?

Azkona, Garikoitz; Sánchez‐Pernaute, Rosario

doi:10.1016/j.pneurobio.2022.102330

Cited by 26 publications

(23 citation statements)

References 94 publications

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“…Moreover, statistics indicate that protocols classified as severe have been decreasing slightly in recent years, by 1% per year [ 65 ]. However, we cannot forget that in order to be able to carry out experiments to refine a technique, in addition to a multidisciplinary team in which veterinarians must play an essential role [ 76 ], financial support is still necessary.…”

Section: Discussionmentioning

confidence: 99%

Refinement in the European Union: A Systematic Review

Díez-Solinska

Vegas

Azkona

2022

Animals

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Refining experiments and housing conditions so as to cause the minimum possible pain and distress is one of the three principles (3Rs) on which Directive 2010/63/EU is based. In this systematic review, we aimed to identify and summarize published advances in the refinement protocols made by European Union-based research groups from 2011 to 2021, and to determine whether or not said research was supported by European or national grants. We included 48 articles, the majority of which were related to improvements in experimental procedures (37/77.1%) for mice (26/54.2%) and were written by research groups belonging to universities (36/57.1%) and from the United Kingdom (21/33.9%). More than two thirds (35/72.9%) of the studies received financial support, 26 (mostly British) at a national level and 8 at a European level. Our results indicated a clear willingness among the scientific community to improve the welfare of laboratory animals, as although funding was not always available or was not specifically granted for this purpose, studies were published nonetheless. However, in addition to institutional support based on legislation, more financial support is needed. We believe that more progress would have been made in refinement during these years if there had been more specific financial support available at both the national and European Union levels since our data suggest that countries investing in refinement have the greatest productivity in successfully publishing refinements.

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Section: Discussionmentioning

confidence: 99%

Refinement in the European Union: A Systematic Review

Díez-Solinska

Vegas

Azkona

2022

Animals

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“…Experimental (animal) models, especially based on rodents, are a valuable tool in translational neuroscience research [ 81 ], helping to target a wide range of brain disorders, including mTORopathies and epilepsy [ 82 ] (see Table 2 for details). For example, young adult male B6-129S4-Tsc2tm1Djk/J mice represent a useful transgenic model of TSC with Tsc2 haploinsufficiency and region-specific alterations in the expression of multiple synaptic proteins [ 83 ].…”

Section: Animal Models Of Mtoropahic Epilepsymentioning

confidence: 99%

Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish

Abreu

Demin

Kotova

et al. 2023

IJMS

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The mammalian target of rapamycin (mTOR) is an important molecular regulator of cell growth and proliferation. Brain mTOR activity plays a crucial role in synaptic plasticity, cell development, migration and proliferation, as well as memory storage, protein synthesis, autophagy, ion channel expression and axonal regeneration. Aberrant mTOR signaling causes a diverse group of neurological disorders, termed ‘mTORopathies’. Typically arising from mutations within the mTOR signaling pathway, these disorders are characterized by cortical malformations and other neuromorphological abnormalities that usually co-occur with severe, often treatment-resistant, epilepsy. Here, we discuss recent advances and current challenges in developing experimental models of mTOR-dependent epilepsy and other related mTORopathies, including using zebrafish models for studying these disorders, as well as outline future directions of research in this field.

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“…These animal models have many limitations and it has been shown that results from mice experiments are rarely predictive of the human outcome [ 9 ]. These problems are even more accentuated in translational neuroscience research, since the brain structure lacks much complexity in rodents and fails to mimic many key features of the human brain [ 10 , 11 ]. Non-human primates can provide more relevant information because of their homology to humans.…”

Section: Introductionmentioning

confidence: 99%

“…However, high costs and the need for special animal facilities, among other limitations, hinder generalization of experiments with these animals. In addition to the lack of predictability, animal experiments are expensive and laborious, and there is an increasing demand from society and regulatory bodies to reduce the number of animals used for research [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Brain Organoids to Evaluate Cellular Therapies

García-Delgado

Campos‐Cuerva

Rosell‐Valle

et al. 2022

Animals

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Animal models currently used to test the efficacy and safety of cell therapies, mainly murine models, have limitations as molecular, cellular, and physiological mechanisms are often inherently different between species, especially in the brain. Therefore, for clinical translation of cell-based medicinal products, the development of alternative models based on human neural cells may be crucial. We have developed an in vitro model of transplantation into human brain organoids to study the potential of neural stem cells as cell therapeutics and compared these data with standard xenograft studies in the brain of immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Neural stem cells showed similar differentiation and proliferation potentials in both human brain organoids and mouse brains. Our results suggest that brain organoids can be informative in the evaluation of cell therapies, helping to reduce the number of animals used for regulatory studies.

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Mice in translational neuroscience: What R we doing?

Cited by 26 publications

References 94 publications

Refinement in the European Union: A Systematic Review

Refinement in the European Union: A Systematic Review

Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish

Brain Organoids to Evaluate Cellular Therapies

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