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Three-Dimensional Analysis of Mouse Habenula Subnuclei Reveals Reduced Volume and Gene Expression in the Lipopolysaccharide-mediated Depression Model

Experimental Neurobiology 2019년 28권 6호 p.709 ~ 719
 ( Yang Esther ) - Korea University College of Medicine Department of Anatomy

 ( Kim Jin-Yong ) - Korea University College of Medicine Department of Anatomy
 ( Yang Soo-Hyun ) - Korea University College of Medicine Department of Anatomy
이은수 ( Lee Eun-Soo ) - Korea University College of Medicine Department of Anatomy
 ( Sun Woong ) - Korea University College of Medicine Department of Anatomy
이현우 ( Lee Hyun-Woo ) - Korea University College of Medicine Department of Anatomy
 ( Kim Hyun ) - Korea University College of Medicine Department of Anatomy

Abstract


The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb. To probe this possibility, we developed 3-dimensional reconstruction methods for the high-resolution volumetric analysis of Hb and the mRNA levels at the given volume in normal or lipopolysaccharide (LPS)-mediated mouse model of depression. Notably, we discovered that the volume reduction was prominent in medial Hb but not in lateral Hb after LPS treatments. On the other hand, the RNA expression levels of known Hb regional markers such as Tac1 (dorsal part of medial Hb), ChAT (ventral part of medial Hb), and Tacr1 (medial and lateral Hb) were all decreased in all Hb subnuclei in LPS-injected mice. Accordingly, accurate volumetry with marker labeling was not feasible. Collectively, these established 3D analyses of mouse Hb successfully and precisely determine the volume-based changes of small brain structure, which should be applicable in a wider range of mouse models or pathological specimens.

키워드

3-dimensional structure; Gene expression; Depression; Habenula
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