ABSTRACT
Purpose@#To elucidate the brain’s intrinsic response to injury, we tracked the response of neural stem/progenitor cells (NSPCs) located in ventricular-subventricular zone (V-SVZ) to hypoxic-ischemic brain injury (HI). We also evaluated whether transduction of V-SVZ NSPCs with neurogenic factor NeuroD1 could enhance their neurogenesis in HI. @*Materials and Methods@#Unilateral HI was induced in ICR neonatal mice. To label proliferative V-SVZ NSPCs in response to HI, bromodeoxyuridine (BrdU) and retroviral particles encoding LacZ or NeuroD1/GFP were injected. The cellular responses of NSPCs were analyzed by immunohistochemistry. @*Results@#Unilateral HI increased the number of BrdU+ newly-born cells in the V-SVZ ipsilateral to the lesion while injury reduced the number of newly-born cells reaching the ipsilateral olfactory bulb, which is the programmed destination of migratory V-SVZ NSPCs in the intact brain. These newly-born cells were directed from this pathway towards the lesions. HI significantly increased the number of newly-born cells in the cortex and striatum by the altered migration of V-SVZ cells. Many of these newly-born cells differentiated into active neurons and glia. LacZ-expressing V-SVZ NSPCs also showed extensive migration towards the non-neurogenic regions ipsilateral to the lesion, and expressed the neuronal marker NeuN. NeuroD1+/GFP+ V-SVZ NSPCs almost differentiated into neurons in the peri-infarct regions. @*Conclusion@#HI promotes the establishment of a substantial number of new neurons in non-neurogenic regions, suggesting intrinsic repair mechanisms of the brain, by controlling the behavior of endogenous NSPCs. The activation of NeuroD1 expression may improve the therapeutic potential of endogenous NSPCs by increasing their neuronal differentiation in HI.
ABSTRACT
PURPOSE: This was a methodological study that aimed to develop a measurement scale for aging anxiety among middle-aged women. METHODS: In this study, construct factors were extracted, and a conceptual framework was established through an extensive literature review and in-depth interviews with middle-aged women. Under the conceptual framework, 44 preliminary items were constructed, and a preliminary scale of 25 items was completed after two rounds of expert validation and item review. For this study, data were collected from 201 women aged 40~59 years, and the construct validity and reliability of the preliminary scale were verified. RESULTS: To verify the construct validity, exploratory factor analysis was conducted. Four factors containing 19 items were extracted. Concurrent validity of the developed scale was verified with Pearson's correlation analysis. The final scale comprised 4 factors ("Social valueless", "Physical weakness", "Concern about changes in appearance", and "Expectations of old age") and 19 items. The Cronbach's α value was .91. CONCLUSION: The scale for measuring aging anxiety in middle-aged women developed in this study validly reflected the peculiarities of aging anxiety in middle-aged women, who experience many physical, emotional, and social changes. The scale can be said to reflect the cultural background, as it reflected real experiences gained through in-depth interviews with middle-aged women.
Subject(s)
Female , Humans , Aging , Anxiety , Methods , Reproducibility of Results , Social ChangeABSTRACT
PURPOSE@#This was a methodological study that aimed to develop a measurement scale for aging anxiety among middle-aged women.@*METHODS@#In this study, construct factors were extracted, and a conceptual framework was established through an extensive literature review and in-depth interviews with middle-aged women. Under the conceptual framework, 44 preliminary items were constructed, and a preliminary scale of 25 items was completed after two rounds of expert validation and item review. For this study, data were collected from 201 women aged 40~59 years, and the construct validity and reliability of the preliminary scale were verified.@*RESULTS@#To verify the construct validity, exploratory factor analysis was conducted. Four factors containing 19 items were extracted. Concurrent validity of the developed scale was verified with Pearson's correlation analysis. The final scale comprised 4 factors ("Social valueless", "Physical weakness", "Concern about changes in appearance", and "Expectations of old age") and 19 items. The Cronbach's α value was .91.@*CONCLUSION@#The scale for measuring aging anxiety in middle-aged women developed in this study validly reflected the peculiarities of aging anxiety in middle-aged women, who experience many physical, emotional, and social changes. The scale can be said to reflect the cultural background, as it reflected real experiences gained through in-depth interviews with middle-aged women.
ABSTRACT
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia. Initial observation of microglia in G2019S transgenic mice revealed a decrease in mitochondrial area and shortage of microglial processes compared with their littermates. Next, we elucidated the molecular mechanisms of these phenotypes. Treatment of BV2 cells and primary microglia with LPS enhanced mitochondrial fission and increased Drp1, a mitochondrial fission marker, as previously reported. Importantly, both phenotypes were rescued by treatment with GSK2578215A, a LRRK2 kinase inhibitor. Finally, the protein levels of CD68, an active microglia marker, Drp1 and TNF-α were significantly higher in brain lysates of G2019S transgenic mice compared with the levels in their littermates. Taken together, our data suggest that LRRK2 could promote microglial mitochondrial alteration via Drp1 in a kinase-dependent manner, resulting in stimulation of pro-inflammatory responses. This mechanism in microglia might be a potential target to develop PD therapy since neuroinflammation by active microglia is a major symptom of PD.