Inwardly rectifying potassium (Kir) 4.1 channels in astrocytes regulate neuronal excitability by mediating spatial potassium buffering. Although dysfunction of astrocytic Kir4.1 channels is implicated in the development of epileptic seizures, the functional mechanisms of Kir4.1 channels in modulating epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1 inhibition (blockade and knockdown) on expression of brain-derived neurotrophic factor (BDNF), a key modulator of epileptogenesis, in the primary cultures of mouse astrocytes. For blockade of Kir4.1 channels, we tested several antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF mRNA expression in a concentration-dependent manner and increased the BDNF protein level. Other antidepressants (e.g., sertraline and imipramine) also increased the expression of BDNF mRNA with relative potencies similar to those for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression by the transfection of small interfering RNA (siRNA) targeting Kir4.1 significantly increased the mRNA and protein levels of BDNF. The BDNF induction by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present results demonstrated that inhibition of Kir4.1 channels facilitates BDNF expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway, which may be linked to the development of epilepsy and other neuropsychiatric disorders.
Background Achieving a desirable death is an urgent aging-related problem in Japan. However, measures of the quality of death and dying in Japan are lacking. This study aimed to identify components of a desirable death in the residents of Kagawa prefecture, Japan, through focus group interviews. Methods A group interview was conducted with 30 residents aged 20–80 ( M age = 50.9, SD = 22.1 years; 43.3% ≥ 65 years; 40.0% unemployed) who had experienced the death of a closely associated person. Participants were grouped into four generations with diverse characteristics (e.g., age, sex, occupation). The interview lasted 1–2 h and involved one interviewer, one observer, and one recorder. The interview theme was “What is a desirable death?” Participants were asked “What do you want to achieve before you die?” or “What would a close friend want to experience when death is near?” We then extracted important items related to “desirable death” using serialization and observation records, while also consulting three analysts. The analysis results of the four generations were ultimately integrated into final categories. Results The most common experience of a familiar death was that of parents, followed by grandparents. Half of participants had witnessed the death. Through category analysis, eight important categories related to desirable death were ultimately extracted. Nine items were identified as common to all generations. While the elderly generation had wide-ranging opinions, the younger generations’ opinions tended to concentrate on satisfaction with life and family relations. Conclusion Eight concepts were extracted as important factors of a desirable death from the residents of Kagawa prefecture, Japan.
In Japan, a rapid pace of aging coupled with the lower birth rates causes the decrease of the population especially in rural area, which leads to the problems with the delivery of healthcare services. We investigated the relationship between the geographical accessibility (time and distance) and the utilization rate of outpatient services in the elderly by major disease groups in Tokushima prefecture, Japan. Distances and driving times to the nearest facilities from residential sites in major disease categories were measured by using geographic information system. Utilization data was obtained from the claim data. In diseases of the musculoskeletal system and connective tissue (M00-M99), diseases of the digestive system (K00-K93), endocrine, nutritional and metabolic diseases (E00-E90), diseases of the eye and adnexa (H00-H59) and diseases of the respiratory system (J00-J99), there were moderate negative correlations (around –0.4 to –0.6) both in distance and time. Distance and time to the nearest facilities were important factors for the utilization of outpatient services of major disease categories in Japanese elderly. Comprehensive approach which include socio- economic factors is needed to mitigate access problems in aging Japanese society
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