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Possible involvement of the cerebellum in motor-function impairment in progranulin-deficient mice

Matsuwaki, Takashi; Kobayashi, Akira; Mase, Kanade; Nakamura, Katsuyuki; Nakano, Shin-Ichi; Miyoshi, Takahiro; Yamanouchi, Keitaro; Nishihara, Masugi

doi: 10.1097/WNR.0000000000000442
CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCE

Progranulin (PGRN) is a multifunctional growth factor involved in many physiological and pathological processes in the brain such as sexual differentiation, neurogenesis, neuroinflammation, and neurodegeneration. Previously, we showed that PGRN was expressed broadly in the brain and the Purkinje cells in the cerebellum were one of the regions with the highest expression level of PGRN. Thus, in the present study, we investigated the possible roles of PGRN in the cerebellum by comparing wild-type (WT) and PGRN-deficient (KO) mice with immunohistochemical staining for calbindin, a marker of Purkinje cells. The results showed that the density of Purkinje cell dendrites in the molecular layer of the cerebellum was significantly higher in KO mice than in WT mice, although the number of cell bodies was comparable between the genotypes. Subsequently, as the cerebellum is the center of the motor function, we performed a rotarod test and found that KO mice remained on the rotating rod for significantly shorter periods than WT mice. However, KO and WT mice did not differ significantly with respect to the diameter of myofibers in a skeletal muscle. These results suggest that PGRN is involved in the development and/or maturation of neuronal networks comprising Purkinje cells in the cerebellum, which may be a prerequisite to normal motor function.

Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

Correspondence to Masugi Nishihara, PhD, Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan Tel: +81 3 5841 5386; fax: +81 3 5841 8017; e-mail: amnishi@mail.ecc.u-tokyo.ac.jp

Received July 13, 2015

Accepted July 24, 2015

© 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins