The continued need for animals to advance brain research

Homberg, Judith R.; Adan, Roger A.H.; Alenina, Natalia; Asiminas, Antonis; Bäder, Michael; Beckers, Tom; Begg, Denovan P.; Blokland, Arjan; Bürger, Marilise Escobar; Dijk, Gertjan van; Eisel, Ulrich; Elgersma, Ype; Englitz, Bernhard; Fernández‐Ruiz, Antonio; Fitzsimons, Carlos P.; Dam, Anne‐Marie van; Gass, Peter; Grandjean, Joanes; Havekes, Robbert; Henckens, Marloes J. A. G.; Herden, Christiane; Hut, Roelof A.; Jarrett, Wendy; Jeffrey, Kate L.; Ježová, Daniela; Kalsbeek, Andries; Kamermans, Maarten; Kas, Martien; Kasri, Nael Nadif; Kiliaan, Amanda J.; Kolk, Sharon M.; Kőrösi, Anikó; Korte, S. Mechiel; Kozicz, Tamás; Kushner, Steven A.; Leech, Kirk; Lesch, Klaus‐Peter; Lesscher, Heidi M. B.; Lucassen, Paul J.; Lüthi, Anita; Ma, Li; Mallien, Anne Stephanie; Meerlo, Peter; Mejías, Jorge F.; Meye, Frank J.; Mitchell, Anna S.; Mul, Joram D.; Olcese, Umberto; González, Azahara Oliva; Olivier, Jocelien; Pasqualetti, Massimo; Pennartz, Cyriel M. A.; Popik, Piotr; Prickaerts, Jos; Prida, Liset Menéndez de la; Ribeiro, Sidarta; Roozendaal, Benno; Rossato, Janine I.; Salari, Ali-Akbar; Schoemaker, Regien G.; Smit, August B.; Vanderschuren, Louk J. M. J.; Takeuchi, Tomonori; Veen, Rixt van der; Smidt, Marten P.; Vyazovskiy, Vladyslav V.; Wiesmann, Maximilian; Wierenga, Corette J.; Williams, Bella; Willuhn, Ingo; Wöhr, Markus; Wolvekamp, M. C. J.; Zee, Eddy A. van der

doi:10.1016/j.neuron.2021.07.015

Cited by 44 publications

(29 citation statements)

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“…Experimental animal models represent an invaluable source of information to explore the contribution of individual genes to human disorders (Homberg et al, 2021). However, null mutant models exhibiting a complete inactivation of a given gene may be inadequately informative in the case of genetically complex diseases, in which each risk gene contributes to vulnerability only modestly.…”

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation

Rivero

Alhama-Riba

et al. 2021

Front. Genet.

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Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.

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Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation

Rivero

Alhama-Riba

et al. 2021

Front. Genet.

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“…There is a continued need for small animals as a powerful model system to advance neuroimaging and translational brain research ( 159 ). The biodistribution and pharmacokinetic information of pharmaceuticals in rodents and ex vivo target validation are prerequisites for phase 1 studies.…”

Section: Organ-on-chip Pharmacokineticsmentioning

confidence: 99%

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

Ren

Guan

et al. 2022

Front. Med.

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Small animal models play a fundamental role in brain research by deepening the understanding of the physiological functions and mechanisms underlying brain disorders and are thus essential in the development of therapeutic and diagnostic imaging tracers targeting the central nervous system. Advances in structural, functional, and molecular imaging using MRI, PET, fluorescence imaging, and optoacoustic imaging have enabled the interrogation of the rodent brain across a large temporal and spatial resolution scale in a non-invasively manner. However, there are still several major gaps in translating from preclinical brain imaging to the clinical setting. The hindering factors include the following: (1) intrinsic differences between biological species regarding brain size, cell type, protein expression level, and metabolism level and (2) imaging technical barriers regarding the interpretation of image contrast and limited spatiotemporal resolution. To mitigate these factors, single-cell transcriptomics and measures to identify the cellular source of PET tracers have been developed. Meanwhile, hybrid imaging techniques that provide highly complementary anatomical and molecular information are emerging. Furthermore, deep learning-based image analysis has been developed to enhance the quantification and optimization of the imaging protocol. In this mini-review, we summarize the recent developments in small animal neuroimaging toward improved translational power, with a focus on technical improvement including hybrid imaging, data processing, transcriptomics, awake animal imaging, and on-chip pharmacokinetics. We also discuss outstanding challenges in standardization and considerations toward increasing translational power and propose future outlooks.

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“…Dedicated legislation is in place to maximize animal welfare (Box 1), and several governmental and non‐governmental organizations have put in place initiatives to promote the development and adoption of alternative, non‐animal‐based methods. Meanwhile, scientists highlight that animal research remains indispensable for biomedical progress and that, currently, the value and applicability of many non‐animal methods remains limited (Genzel et al , 2020; Homberg et al , 2021).…”

Section: Introductionmentioning

confidence: 99%

Do we still need animals? Surveying the role of animal‐free models in Alzheimer’s and Parkinson’s disease research

et al. 2022

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The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the “3R” principle of “Refining, Reducing and Replacing” animal experiments, and across the globe, different initiatives stimulate the use of animal‐free methods. Based on an extensive literature screen to map the development and adoption of animal‐free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal‐derived models. Among the animal‐free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal‐free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non‐animal‐based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal‐free approaches.

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The continued need for animals to advance brain research

Cited by 44 publications

References 10 publications

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

Do we still need animals? Surveying the role of animal‐free models in Alzheimer’s and Parkinson’s disease research

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