Jill L Silverman1, Jacob Ellegood2. 1. MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California, USA. 2. Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Canada.
Abstract
PURPOSE OF REVIEW: This review highlights the invaluable contribution of in-vivo rodent models in dissecting the underlying neurobiology for numerous neurodevelopmental disorders. Currently, models are routinely generated with precision genomics and characterized for research on neurodevelopmental disorders. In order to impact translation, outcome measures that are translationally relevant are essential. This review emphasizes the importance of accurate neurobehavioral and anatomical analyses. RECENT FINDINGS: Numerous well validated assays for testing alterations across behavioral domains with sensitivity and throughput have become important tools for studying the effects of genetic mutations on neurodevelopment. Recent work has highlighted relationships and links between behavioral outcomes and various anatomical metrics from neuroimaging via magnetic resonance. These readouts are biological markers and outcome measures for translational research and will be have important roles for genetic or pharmacologic intervention strategies. SUMMARY: Combinatorial approaches that leverage translationally relevant behavior and neuroanatomy can be used to develop a platform for assessment of cutting edge preclinical models. Reliable, robust behavioral phenotypes in preclinical model systems, with clustering of brain disease will lead to well informed, precise biochemical mechanistic hypotheses. Ultimately, these steadfast workhorse techniques will accelerate the progress of developing and testing targeted treatments for multiple neurodevelopmental disorders.
PURPOSE OF REVIEW: This review highlights the invaluable contribution of in-vivo rodent models in dissecting the underlying neurobiology for numerous neurodevelopmental disorders. Currently, models are routinely generated with precision genomics and characterized for research on neurodevelopmental disorders. In order to impact translation, outcome measures that are translationally relevant are essential. This review emphasizes the importance of accurate neurobehavioral and anatomical analyses. RECENT FINDINGS: Numerous well validated assays for testing alterations across behavioral domains with sensitivity and throughput have become important tools for studying the effects of genetic mutations on neurodevelopment. Recent work has highlighted relationships and links between behavioral outcomes and various anatomical metrics from neuroimaging via magnetic resonance. These readouts are biological markers and outcome measures for translational research and will be have important roles for genetic or pharmacologic intervention strategies. SUMMARY: Combinatorial approaches that leverage translationally relevant behavior and neuroanatomy can be used to develop a platform for assessment of cutting edge preclinical models. Reliable, robust behavioral phenotypes in preclinical model systems, with clustering of brain disease will lead to well informed, precise biochemical mechanistic hypotheses. Ultimately, these steadfast workhorse techniques will accelerate the progress of developing and testing targeted treatments for multiple neurodevelopmental disorders.
Authors: Jacob Ellegood; Brooke A Babineau; R Mark Henkelman; Jason P Lerch; Jacqueline N Crawley Journal: Neuroimage Date: 2012-12-26 Impact factor: 6.556
Authors: Brian J Nieman; Nicholas A Bock; Johnathan Bishop; John G Sled; X Josette Chen; R Mark Henkelman Journal: Magn Reson Med Date: 2005-09 Impact factor: 4.668
Authors: Nancy Merner; Baudouin Forgeot d'Arc; Scott C Bell; Gilles Maussion; Huashan Peng; Julie Gauthier; Liam Crapper; Fadi F Hamdan; Jacques L Michaud; Laurent Mottron; Guy A Rouleau; Carl Ernst Journal: Am J Med Genet A Date: 2016-01-20 Impact factor: 2.802
Authors: Mark D Shen; Sun Hyung Kim; Robert C McKinstry; Hongbin Gu; Heather C Hazlett; Christine W Nordahl; Robert W Emerson; Dennis Shaw; Jed T Elison; Meghan R Swanson; Vladimir S Fonov; Guido Gerig; Stephen R Dager; Kelly N Botteron; Sarah Paterson; Robert T Schultz; Alan C Evans; Annette M Estes; Lonnie Zwaigenbaum; Martin A Styner; David G Amaral; J Piven; H C Hazlett; C Chappell; S Dager; A Estes; D Shaw; K Botteron; R McKinstry; J Constantino; J Pruett; R Schultz; L Zwaigenbaum; J Elison; A C Evans; D L Collins; G B Pike; V Fonov; P Kostopoulos; S Das; G Gerig; M Styner; H Gu; Joseph Piven Journal: Biol Psychiatry Date: 2017-03-06 Impact factor: 13.382
Authors: Jill L Silverman; Audrey Thurm; Sarah B Ethridge; Makayla M Soller; Stela P Petkova; Ted Abel; Melissa D Bauman; Edward S Brodkin; Hala Harony-Nicolas; Markus Wöhr; Alycia Halladay Journal: Genes Brain Behav Date: 2022-03-14 Impact factor: 3.708
Authors: Robert J Thorn; Amanda Dombroski; Kerry Eller; Tania M Dominguez-Gonzalez; Danielle E Clift; Peter Baek; Renee J Seto; Elizabeth S Kahn; Sara K Tucker; Ruth M Colwill; Jason K Sello; Robbert Creton Journal: Sci Rep Date: 2019-09-27 Impact factor: 4.379
Authors: J Ellegood; S P Petkova; J L Silverman; J P Lerch; A Kinman; L R Qiu; A Adhikari; A A Wade; D Fernandes; Z Lindenmaier; A Creighton; L M J Nutter; A S Nord Journal: Mol Autism Date: 2021-03-23 Impact factor: 7.509
Authors: E L Berg; M C Pride; S P Petkova; R D Lee; N A Copping; Y Shen; A Adhikari; T A Fenton; L R Pedersen; L S Noakes; B J Nieman; J P Lerch; S Harris; H A Born; M M Peters; P Deng; D L Cameron; K D Fink; U Beitnere; H O'Geen; A E Anderson; S V Dindot; K R Nash; E J Weeber; M Wöhr; J Ellegood; D J Segal; J L Silverman Journal: Transl Psychiatry Date: 2020-01-27 Impact factor: 6.222