Brain Morphological Analysis in Mice with Hyperactivation of the Hedgehog Signaling Pathway

Overview

Journal Front Neurosci

Date 2024 Sep 18

PMID 39290714

Authors

Tadashi Shiohama

Hideki Uchikawa

Nobuhiro Nitta

Tomozumi Takatani

Shingo Matsuda

Alpen Ortug

Emi Takahashi

Daisuke Sawada

Eiji Shimizu

Katsunori Fujii

Ichio Aoki

Hiromichi Hamada

Affiliations

Soon will be listed here.

Abstract

Hedgehog signaling is a highly conserved pathway that plays pivotal roles in morphogenesis, tumorigenesis, osteogenesis, and wound healing. Previous investigations in patients with Gorlin syndrome found low harm avoidance traits, and increased volumes in the cerebrum, cerebellum, and cerebral ventricles, suggesting the association between brain morphology and the constitutive hyperactivation of hedgehog signaling, while the changes of regional brain volumes in upregulated hedgehog signaling pathway remains unclear so far. Herein, we investigated comprehensive brain regional volumes using quantitative structural brain MRI, and identified increased volumes of amygdala, striatum, and pallidum on the global segmentation, and increased volumes of the lateral and medial parts of the central nucleus of the amygdala on the detail segmentation in heterozygous deletion mice. Our data may enhance comprehension of the association between brain morphogenic changes and hyperactivity in hedgehog signaling.

References

Calhoon G, Tye K . Resolving the neural circuits of anxiety. Nat Neurosci. 2015; 18(10):1394-404. PMC: 7575249. DOI: 10.1038/nn.4101. View

Peirson A, Heuchert J, Thomala L, Berk M, Plein H, Cloninger C . Relationship between serotonin and the temperament and character inventory. Psychiatry Res. 2000; 89(1):29-37. DOI: 10.1016/s0165-1781(99)00079-7. View

Vaillant C, Monard D . SHH pathway and cerebellar development. Cerebellum. 2009; 8(3):291-301. DOI: 10.1007/s12311-009-0094-8. View

Hikishima K, Komaki Y, Seki F, Ohnishi Y, Okano H, Okano H . In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain. Sci Rep. 2017; 7(1):85. PMC: 5427914. DOI: 10.1038/s41598-017-00148-1. View

Kiyasova V, Gaspar P . Development of raphe serotonin neurons from specification to guidance. Eur J Neurosci. 2011; 34(10):1553-62. DOI: 10.1111/j.1460-9568.2011.07910.x. View

Hubner N, Mechling A, Lee H, Reisert M, Bienert T, Hennig J . The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model. Neuroimage. 2016; 146:1-18. DOI: 10.1016/j.neuroimage.2016.11.008. View

Nees F, Ruttorf M, Fuchs X, Rance M, Beyer N . Volumetric brain correlates of approach-avoidance behavior and their relation to chronic back pain. Brain Imaging Behav. 2019; 14(5):1758-1768. DOI: 10.1007/s11682-019-00110-x. View

Wang J, Ware K, Bedolla A, Allgire E, Turcato F, Weed M . Disruption of Sonic Hedgehog Signaling Accelerates Age-Related Neurogenesis Decline and Abolishes Stroke-Induced Neurogenesis and Leads to Increased Anxiety Behavior in Stroke Mice. Transl Stroke Res. 2022; 13(5):830-844. PMC: 10114538. DOI: 10.1007/s12975-022-00994-w. View

Klein S, Staring M, Murphy K, Viergever M, Pluim J . elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2009; 29(1):196-205. DOI: 10.1109/TMI.2009.2035616. View

10.

Stockings E, Hall W, Lynskey M, Morley K, Reavley N, Strang J . Prevention, early intervention, harm reduction, and treatment of substance use in young people. Lancet Psychiatry. 2016; 3(3):280-96. DOI: 10.1016/S2215-0366(16)00002-X. View

11.

Kirihara Y, Takechi M, Kurosaki K, Kobayashi Y, Kurosawa T . Anesthetic effects of a mixture of medetomidine, midazolam and butorphanol in two strains of mice. Exp Anim. 2013; 62(3):173-80. PMC: 4160945. DOI: 10.1538/expanim.62.173. View

12.

Peh O, Rapisarda A, Lee J . Childhood adversities in people at ultra-high risk (UHR) for psychosis: a systematic review and meta-analysis. Psychol Med. 2019; 49(7):1089-1101. DOI: 10.1017/S003329171800394X. View

13.

Hodge R, Bakken T, Miller J, Smith K, Barkan E, Graybuck L . Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019; 573(7772):61-68. PMC: 6919571. DOI: 10.1038/s41586-019-1506-7. View

14.

Koch S, Mueller S, Foddis M, Bienert T, von Elverfeldt D, Knab F . Atlas registration for edema-corrected MRI lesion volume in mouse stroke models. J Cereb Blood Flow Metab. 2017; 39(2):313-323. PMC: 6360485. DOI: 10.1177/0271678X17726635. View

15.

Uchikawa H, Fujii K, Shiohama T, Nakazato M, Shimizu E, Miyashita T . Specific temperament in patients with nevoid basal cell carcinoma syndrome. Pediatr Int. 2020; 63(2):177-182. DOI: 10.1111/ped.14419. View

16.

Goodrich L, Milenkovic L, Higgins K, Scott M . Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 1997; 277(5329):1109-13. DOI: 10.1126/science.277.5329.1109. View

17.

Cloninger C . A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry. 1987; 44(6):573-88. DOI: 10.1001/archpsyc.1987.01800180093014. View

18.

Radonjic N, Memi F, Ortega J, Glidden N, Zhan H, Zecevic N . The Role of Sonic Hedgehog in the Specification of Human Cortical Progenitors In Vitro. Cereb Cortex. 2014; 26(1):131-43. PMC: 4677972. DOI: 10.1093/cercor/bhu183. View

19.

Hung H, Hsiao Y, Gean P . Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory. Eur Neuropsychopharmacol. 2015; 25(10):1723-32. DOI: 10.1016/j.euroneuro.2015.07.005. View

20.

Aviles E, Wilson N, Stoeckli E . Sonic hedgehog and Wnt: antagonists in morphogenesis but collaborators in axon guidance. Front Cell Neurosci. 2013; 7:86. PMC: 3677135. DOI: 10.3389/fncel.2013.00086. View