Abstract. The progranulin (PGRN) gene is involved in sexual differentiation of the brain during the perinatal period and estrogen-induced adult neurogenesis in the hippocampus. Mutations in the PGRN gene are also implicated in human frontotemporal lobar degeneration. Thus, while PGRN appears to play important roles as a growth factor in the brain, the localization of PGRN-expressing cells throughout the brain has not been fully established. In the present study, we examined the localization of PGRN proteins in the brain using adult male wild-type mice and PGRNdeficient mice we had generated previously. We also evaluated age-dependent changes in PGRN expression at the mRNA and protein levels. As expected, no immunoreactivity was observed in the brains of the PGRN-deficient mice. In the wild-type mice, intense immunoreactivity was observed in several brain regions including the cingulate and piriform cortices, the pyramidal cell layer and dentate gyrus of the hippocampus, the amygdala, the ventromedial and arcuate nuclei of the hypothalamus and the Purkinje cell layer in the cerebellum. Moreover, PGRN mRNA and protein expression decreased in the cortex, hippocampus and hypothalamus in an age-dependent manner. Since many of these brain regions are involved in emotion, memory and recognition, PGRN may play roles as a growth factor in these brain functions that decline with age. Key words: Aging, Brain, Gene expression, Immunohistochemistry, Progranulin (J. Reprod. Dev. 57: [113][114][115][116][117][118][119] 2011) he progranulin (PGRN) gene spans approximately 6.3 kbp and encodes a 68.5-kDa protein containing 7.5 tandem granulin motif repeats [1]. PGRN mRNA is expressed in various tissues and organs, including the reproductive organs, gastrointestinal tract, endocrine organs and neural tissues [2,3]. The PGRN protein is processed into peptides of approximately 6 kDa called granulins [2,4], also known as epithelins [5]. Although both PGRN and granulins have growth-modulating effects on many types of cells in culture [4,5], little is known about their precise molecular mechanisms of action.We have identified PGRN as one of the genes that are upregulated in the hypothalamus by sex steroids during the perinatal period and are involved in sexual differentiation of the rat brain [6][7][8][9]. In addition, we also suggested that PGRN plays a role in mediating the mitogenic effects of estrogen in the hippocampus of adult rats [10]. Subsequently, we generated a line of mice lacking the PGRN gene and found that PGRN-deficient mice exhibited enhanced anxiety and decreased male sexual behavior, suggesting that PGRN is indeed involved in masculinization of the rodent brain [11]. Recently, PGRN has been identified as one of the major factors causing frontotemporal lobar degeneration (FTLD) in humans. In studies on the frequency of mutations in the FTLD population, 5-10% of the patients were found to have mutations in the PGRN gene [12,13]. Taken together, these observations suggest that PGRN plays important roles in the brain ...

We have previously suggested that progranulin mediates the stimulatory effects of estrogen on adult neurogenesis in the hippocampus. Neurogenesis in mature animals is enhanced by growth factors, environmental enrichment, and voluntary exercise. In this study, we investigated the role of progranulin in voluntary running-induced hippocampal neurogenesis. In the hippocampus of wild-type mice, the pyramidal neurons in the CA1 and CA3 regions and interneurons in the hilus were mainly immunoreactive for progranulin, and wheel running increased progranulin expression in these neurons. Wheel running also increased the number of proliferating cells in the hippocampus in wild-type mice, but not in progranulin-deficient mice. These results suggest that progranulin plays an indispensable role in enhancing the hippocampal neurogenesis induced by voluntary exercise.

Blind smartphone users are on the rise and they need to know which device is easiest for them to use. To explore the optimal touchscreen size for devices used by the blind, we conducted an experiment in which 15 blind participants searched for target icons with four touchscreen devices ranging in size from 4 to 7.9 inches. We analyzed the search time, search strategies, and subjective evaluations and found that the 4.7-inch screen device produced the shortest search time and obtained the highest subjective rating among the four devices. These findings are consistent with those in a previous study with sighted participants. One interesting difference is that the blind participants in this study found the icons about 20% to 40% faster than the sighted participants. Another important finding is that the search strategy had a larger effect than the screen size on the search time. These findings are useful for blind people and their supporters at the stage of obtaining new smartphones and learning how to use them.