The inwardly rectifying potassium (Kir) channel Kir4.1 in brain astrocytes mediates spatial K+ buffering and regulates neural activities. Recent studies have shown that loss-of-function mutations in the human gene KCNJ10 encoding Kir4.1 cause epileptic seizures, suggesting a close relationship between the Kir4.1 channel function and epileptogenesis. Here, we performed expressional analysis of Kir4.1 in a pilocarpine-induced rat model of temporal lobe epilepsy (TLE) to explore the role of Kir4.1 channels in modifying TLE epileptogenesis. Treatment of rats with pilocarpine (350 mg/kg, i.p.) induced acute status epilepticus, which subsequently caused spontaneous seizures 7–8 weeks after the pilocarpine treatment. Western blot analysis revealed that TLE rats (interictal condition) showed significantly higher levels of Kir4.1 than the control animals in the cerebral cortex, striatum, and hypothalamus. However, the expression of other Kir subunits, Kir5.1 and Kir2.1, remained unaltered. Immunohistochemical analysis illustrated that Kir4.1-immunoreactivity-positive astrocytes in the pilocarpine-induced TLE model were markedly increased in most of the brain regions examined, concomitant with an increase in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. In addition, Kir4.1 expression ratios relative to the number of astrocytes (Kir4.1-positive cells/GFAP-positive cells) were region-specifically elevated in the amygdala (i.e., medial and cortical amygdaloid nuclei) and sensory cortex. The present study demonstrated for the first time that the expression of astrocytic Kir4.1 channels was elevated in a pilocarpine-induced TLE model, especially in the amygdala, suggesting that astrocytic Kir4.1 channels play a role in modifying TLE epileptogenesis, possibly by acting as an inhibitory compensatory mechanism.
Background:The inwardly rectifying potassium channel subunit Kir4.1 is specifically expressed in astrocytes, which mediates spatial K + buffering and is implicated in the pathogenesis of convulsive epileptic disorders (i.e. generalized tonic-clonic (GTC) and temporal lobe seizures). Objectives: This study aimed to explore the pathophysiological role of Kir4.1 channels in modulating absence seizure incidence, using a spontaneously epileptic animal model. Materials and Methods: Groggy rats, a rat model of human absence seizures, and Slc:Wistar (control) rats, were used in this study. Cortical and hippocampal EEG were recorded to confirm the seizure incidence in Groggy rats. The expression levels of Kir subunits (i.e. Kir4.1, Kir5.1 and Kir2.1) in ten brain regions were analyzed by Western blotting. Results: Groggy rats showed a high incidence (ca. 350 seconds total duration/15 minutes observation period) of absence-like seizures, which were characterized by a sudden immobile posture and synchronously-associated spike and wave discharges. However, Western blot analysis revealed that Kir4.1 expression in Groggy rats was not significantly different from that of control rats in any of the brain regions examined (e.g. cerebral cortex, striatum, hippocampus, diencephalon, midbrain, pons/medulla oblongata and cerebellum). In addition, expressional levels of Kir5.1 and Kir2.1, which are also expressed in astrocytes, were unaltered in Groggy rats.
Conclusions:The present results suggest that unlike GTC and temporal lobe seizures, pathophysiological alterations (e.g. dysfunction and/or expressional changes) of Kir4.1 are not linked to non-convulsive absence seizures.
We often come across differences in the severity of androgenetic alopecia (AGA) as assessed subjectively by the patients themselves and objectively by the attending physicians. For the purpose of examining the differences in the assessment of AGA between patients and physicians, we presented the Norwood classification to male patients and the Shiseido classification to female patients and asked them to assess the degree of hair loss by themselves. We compared the results with the severity as assessed by 2 specified dermatologists. The results show that the assessments of the severity of AGA were consistent between the patients and physicians in 42% (15/36) of cases, the physicians reported a higher grade of severity than the patients themselves in 30% (11/36) of cases, and the patients reported a higher grade of severity than the physicians in 28% (10/36) of cases; however, the Wilcoxon signed rank statistical analysis showed no significant difference between the patients and physicians assessments. AGA should be treated in accordance with individual symptoms and wishes and not a standardized treatment protocol.
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