title: Possible involvement of the cerebellum in motor-function impairment in progranulin-deficient mice.
abstract: 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.
authors: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors: Takashi
authors: T
authors: Matsuwaki
authors: Akira
authors: A
authors: Kobayashi
authors: Kanade
authors: K
authors: Mase
authors: Katsuyuki
authors: K
authors: Nakamura
authors: Shin-Ichi
authors: S
authors: Nakano
authors: Takahiro
authors: T
authors: Miyoshi
authors: Keitaro
authors: K
authors: Yamanouchi
authors: Masugi
authors: M
authors: Nishihara
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D000077155:Granulins; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009069:Movement Disorders / Q000473:pathology / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology; D009434:Neural Pathways / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D000077153:Progranulins; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D045442:Rotarod Performance Test
chemical_list: D064026:Calbindins; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins