Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H2O2). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H2O2 across biological membranes, in skin cells, and its effects in mitigating H2O2-induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H2O2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H2O2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H2O2-treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H2O2-induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

The prevalence of IgE positivity, environmental factors, and clinical implications associated with mite species in allergic patients in Taiwan.

BACKGROUND: Allergic diseases are a growing public health concern with increasing prevalence and severity. Allergens play significant roles in triggering immune responses and the development of allergic reactions. OBJECTIVE: Investigate the presence and clinical significance of dust mites, storage mites, and predatory mite Cheyletus eruditus(Ce) in household environments. METHODS: A survey of household dust was performed to determine mite occurrence and analyze influencing factors, an analysis of the correlation between mite species and allergic symptoms, and basophil activation triggered by mite allergens. Cross-reactivity between Ce and house dust mites was assessed. RESULTS: The high appearance rate of mite species in households of Taiwan was Dermatophagoides pteronyssinus (Dp) and D. farinae(Df). Environmental factors such as pet keeping, vacuum cleaner usage, air conditioner usage, proximity to the kitchen, cleaning frequency, and protein concentration in beds were shown to influence mite prevalence. The appearance of Dp and Df significantly increased the occurrence of airway and nasal symptoms, while the presence of Ce was strongly correlated with skin symptoms. The activation of basophils and the correlation between specific IgE levels and allergic symptoms in response to Ce exposure were demonstrated. The presence of Ce was associated with elevated levels of allergens in bedding. The IgE adsorption between mite species was demonstrated suggesting cross-reactivity between the Ce and Dp was limited. Presence of Ce is associated with elevated levels of major mite allergens in beddings. CONCLUSION: Allergenicity of Ce was confirmed by IgE reactivity and basophil activation regarding mite infestation as a potential cause of skin-related allergy.

Linking tonic and phasic pupil responses to P300 amplitude in an emotional face-word Stroop task.

The locus coeruleus-norepinephrine (LC-NE) system, which regulates arousal levels, is important for cognitive control, including emotional conflict resolution. Additionally, the LC-NE system is implicated in P300 generation. If the P300 is mediated by the LC-NE system, and considering the established correlations between LC activity and pupil dilation, P300 amplitude should correlate with task-evoked (phasic) pupil dilation on a trial-by-trial basis. However, prior studies, predominantly utilizing oddball-type paradigms, have not demonstrated correlations between concurrently recorded task-evoked pupil dilation and P300 responses. Using a recently developed emotional face-word Stroop task that links pupil dilation to the LC-NE system, here, we examined both intra- and inter-individual correlations between task-evoked pupil dilation and P300 amplitude. We found that lower accuracy, slower reaction times, and larger task-evoked pupil dilation were obtained in the incongruent compared to the congruent condition. Furthermore, we observed intra-individual correlations between task-evoked pupil dilation and P300 amplitude, with larger pupil dilation correlating with a greater P300 amplitude. In contrast, pupil dilation did not exhibit consistent correlations with N450 and N170 amplitudes. Baseline (tonic) pupil size also showed correlations with P300 and N170 amplitudes, with smaller pupil size corresponding to larger amplitude. Moreover, inter-individual differences in task-evoked pupil dilation between the congruent and incongruent conditions correlated with differences in reaction time and P300 amplitude, though these effects only approached significance. To summarize, our study provides evidence for a connection between task-evoked pupil dilation and P300 amplitude at the single-trial level, suggesting the involvement of the LC-NE system in P300 generation.

Acrolein adducts and responding autoantibodies correlate with metabolic disturbance in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is caused by many intertwining pathologies involving metabolic aberrations. Patients with metabolic syndrome (MetS) generally show hyperglycemia and dyslipidemia, which can lead to the formation of aldehydic adducts such as acrolein on peptides in the brain and blood. However, the pathogenesis from MetS to AD remains elusive. METHODS: An AD cell model expressing Swedish and Indiana amyloid precursor protein (APP-Swe/Ind) in neuro-2a cells and a 3xTg-AD mouse model were used. Human serum samples (142 control and 117 AD) and related clinical data were collected. Due to the involvement of MetS in AD, human samples were grouped into healthy control (HC), MetS-like, AD with normal metabolism (AD-N), and AD with metabolic disturbance (AD-M). APP, amyloid-beta (Aß), and acrolein adducts in the samples were analyzed using immunofluorescent microscopy, histochemistry, immunoprecipitation, immunoblotting, and/or ELISA. Synthetic Aß1-16 and Aß17-28 peptides were modified with acrolein in vitro and verified using LC-MS/MS. Native and acrolein-modified Aß peptides were used to measure the levels of specific autoantibodies IgG and IgM in the serum. The correlations and diagnostic power of potential biomarkers were evaluated. RESULTS: An increased level of acrolein adducts was detected in the AD model cells. Furthermore, acrolein adducts were observed on APP C-terminal fragments (APP-CTFs) containing Aß in 3xTg-AD mouse serum, brain lysates, and human serum. The level of acrolein adducts was correlated positively with fasting glucose and triglycerides and negatively with high-density lipoprotein-cholesterol, which correspond with MetS conditions. Among the four groups of human samples, the level of acrolein adducts was largely increased only in AD-M compared to all other groups. Notably, anti-acrolein-Aß autoantibodies, especially IgM, were largely reduced in AD-M compared to the MetS group, suggesting that the specific antibodies against acrolein adducts may be depleted during pathogenesis from MetS to AD. CONCLUSIONS: Metabolic disturbance may induce acrolein adduction, however, neutralized by responding autoantibodies. AD may be developed from MetS when these autoantibodies are depleted. Acrolein adducts and the responding autoantibodies may be potential biomarkers for not only diagnosis but also immunotherapy of AD, especially in complication with MetS.

Reduction or enhancement? Repetition effects on early brain potentials during visual word recognition are frequency dependent.

Most studies on word repetition have demonstrated that repeated stimuli yield reductions in brain activity. Despite the well-known repetition reduction effect, some literature reports repetition enhancements in electroencephalogram (EEG) activities. However, although studies of object and face recognition have consistently demonstrated both repetition reduction and enhancement effects, the results of repetition enhancement effects were not consistent in studies of visual word recognition. Therefore, the present study aimed to further investigate the repetition effect on the P200, an early event-related potential (ERP) component that indexes the coactivation of lexical candidates during visual word recognition. To achieve a high signal-to-noise ratio, EEG signals were decomposed into various modes by using the Hilbert-Huang transform. Results demonstrated a repetition enhancement effect on P200 activity in alpha-band oscillation and that lexicality and orthographic neighborhood size would influence the magnitude of the repetition enhancement effect on P200. These findings suggest that alpha activity during visual word recognition might reflect the coactivation of orthographically similar words in the early stages of lexical processing. Meantime, there were repetition reduction effects on ERP activities in theta-delta band oscillation, which might index that the lateral inhibition between lexical candidates would be omitted in repetition.

Antioxidative Activities of Micronized Solid-State Cultivated Hericium erinaceus Rich in Erinacine A against MPTP-Induced Damages.

The Lion's mane mushroom (Hericium erinaceus, HE) is a traditional medical mushroom with high nutritional and economic value. HE possesses anticancer, antimicrobial, antioxidant, immunomodulating, neurotrophic, and neuroprotective activities. The present study evaluated the protection and antioxidative activities of micronized mycelium of HE (HEM) in mice treated with 1-methyl-4-phenylpyridinium (MPTP). HEM was cultivated via solid-state fermentation and micronized using cell wall-breaking technology to increase its bioavailability when ingested. Erinacine A, the bioactive compound in the HEM, played a pivotal role in antioxidant defense. We found that micronized HEM could recover the dopamine level in the mice striatum in a dose-dependent manner that had been greatly reduced during MPTP treatment. Moreover, the malondialdehyde (MDA) and carbonyl levels were reduced in the livers and brains of the MPTP + HEM-treated groups compared with the MPTP group. Additionally, antioxidant enzyme activities, including catalase, superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione reductase (GRd), were elevated after the administration of HEM in MPTP-treated mice in a dose-dependent manner. Taken together, our data indicate that HEM cultivated via solid-state fermentation and processed with cell wall-breaking technology showed an excellent antioxidant efficacy.

Immunomodulatory effects of modified Liu-Wei-Di-Huang-Wan Traditional Chinese medicine on allergic asthmatic mice.

BACKGROUND: Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma. METHODS: This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice. RESULTS: At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL-4, IL-5, and IL-13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung. CONCLUSION: It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.

Elevated alanine aminotransferase is associated with biphasic insulin secretion in the healthy elderly Han Chinese population.

OBJECTIVE: To evaluate the relationship between alanine transaminase (ALT) level and biphasic insulin secretion (BPIS) in healthy elderly Han Chinese individuals. METHODS: This cross-sectional study enrolled healthy elderly participants aged ≥60 years that were part of a health examination programme. In order to explore the correlation and severity of the clinical condition, those with any possible confounding factors known to affect insulin secretion or liver function were excluded from the study. BPIS was calculated using an equation developed previously by this research team. RESULTS: This study enrolled 39 845 healthy elderly individuals (19 058 males and 20 787 females). Participants were stratified into four quartile groups according to their ALT level. In both males and females, the increasing ALT quartiles (ordinal variable) were associated with greater values of log-transformed first-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS). The correlation and the linear regression model showed that increasing ALT level was significantly correlated with higher log-transformed FPIS and SPIS. CONCLUSIONS: ALT was positively correlated with BPIS in a healthy elderly population in both men and women. Elevated ALT may serve as an indicating factor for developing metabolic syndrome and type 2 diabetes mellitus in healthy elderly individuals.

Application of Empirical Mode Decomposition for Decoding Perception of Faces Using Magnetoencephalography.

Neural decoding is useful to explore the timing and source location in which the brain encodes information. Higher classification accuracy means that an analysis is more likely to succeed in extracting useful information from noises. In this paper, we present the application of a nonlinear, nonstationary signal decomposition technique-the empirical mode decomposition (EMD), on MEG data. We discuss the fundamental concepts and importance of nonlinear methods when it comes to analyzing brainwave signals and demonstrate the procedure on a set of open-source MEG facial recognition task dataset. The improved clarity of data allowed further decoding analysis to capture distinguishing features between conditions that were formerly over-looked in the existing literature, while raising interesting questions concerning hemispheric dominance to the encoding process of facial and identity information.

Effects of Phonological Consistency and Semantic Radical Combinability on N170 and P200 in the Reading of Chinese Phonograms.

Studies have suggested that visually presented words are obligatorily decomposed into constituents that could be mapped to language representations. The present study aims to elucidate how orthographic processing of one constituent affects the other and vice versa during a word recognition task. Chinese orthographic system has characters representing syllables and meanings instead of suffixation roles, and the majority of Chinese characters are phonograms that can be further decomposed into phonetic radical and semantic radical. We propose that semantic radical combinability indexed by semantic radicals and the effect of phonological consistency indexed by phonetic radicals would interact with each other during the reading of Chinese phonograms. Twenty-six right-handed native Chinese speakers were recruited to the study. Participants were presented with phonograms divided into four conditions following their semantic radical combinability (large vs. small) and phonological consistency (high vs. low). EEG signals were recorded throughout the covert naming task. Our results show that there is an interaction effect between phonological consistency and semantic radical combinability on the right hemisphere N170 activity while reading phonograms. Semantic radical combinability influenced the right hemisphere N170 during the process of low-consistency character reading but not high-consistency character reading. On the other hand, the left hemisphere N170 revealed a more significant activity during reading high-consistency characters and was not affected by radical combinability. In addition, while low-consistency characters revealed a larger P200 than high-consistency characters, the semantic radical combinability effect on P200 was only significant when participants were reading high-consistency characters but not low-consistency characters. These results provide new information about how ERPs are involved in word recognition within the context of interaction among orthographic and phonological dimensions.

A Minimum Temporal Window for Direction Detection of Frequency-Modulated Sweeps: A Magnetoencephalography Study.

The ability to rapidly encode the direction of frequency contour contained in frequency-modulated (FM) sweeps is essential for speech processing, music appreciation, and conspecific communications. Psychophysical evidence points to a common temporal window threshold for human listeners in processing rapid changes in frequency glides. No neural evidence has been provided for the existence of a cortical temporal window threshold underlying the encoding of rapid transitions in frequency glides. The present magnetoencephalography study used the cortical mismatch negativity activity (MMNm) to investigate the minimum temporal window required for detecting different magnitudes of directional changes in frequency-modulated sweeps. A deviant oddball paradigm was used in which directional upward or downward frequency sweep serves as the standard and the same type of sweep with the opposite direction serves as its deviant. Stimuli consisted of unidirectional linear frequency-sweep complexes that swept across speech-relevant frequency bands in durations of 10, 20, 40, 80, 160, and 320 ms (with corresponding rates of 50, 25, 12.5, 6.2, 3.1, 1.5 oct/s). The data revealed significant magnetic mismatch field responses across all sweep durations, with slower-rate sweeps eliciting larger MMNm responses. A greater temporally related enhancement in MMNm response was obtained for rising but not falling frequency sweep contours. A hemispheric asymmetry in the MMNm response pattern was observed corresponding to the directionality of frequency sweeps. Contrary to psychophysical findings, we report a temporal window as short as 10 ms sufficient to elicit a robust MMNm response to a directional change in speech-relevant frequency contours. The results suggest that auditory cortex requires extremely brief temporal window to implicitly differentiate a dynamic change in frequency of linguistically relevant pitch contours. That the brain is extremely sensitive to fine spectral changes contained in speech-relevant glides provides cortical evidence for the ecological importance of FM sweeps in speech processing.

Occurrence of complete heart block associated with acute renal infarction.

Complete heart block (CHB) and acute renal infarction (ARI) are both uncommon diseases and seldom encountered in the clinical practice. We describe a rare case of pre-existing left bundle branch block, presenting simultaneously with CHB and ARI. The possible mechanism depends on prior presence of either CHB or ARI. If ARI occurs first, severe pain and embolism may enhance the vagal tone resulting in decrease in the heart rate and transient intraventricular conduction interruption, which subsequently causes CHB. The opposite scenario, CHB preceding ARI, is also possible. CHB can be physiologic and transient, with higher risk of development in the circumstance of pre-existing conduction system disturbances. Patients with CHB are predisposed to formation of thrombi and thromboemboli, giving rise to ARI. In conclusion, awareness and timely identification of the clinical manifestations of these two diseases may facilitate early diagnosis and prompt management.

Correction: Effect of body mass index on diabetogenesis factors at a fixed fasting plasma glucose level.

[This corrects the article DOI: 10.1371/journal.pone.0189115.].

Effect of body mass index on diabetogenesis factors at a fixed fasting plasma glucose level.

AIM: The present study evaluated the relative influence of body mass index (BMI) on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting plasma glucose level in an older ethnic Chinese population. METHODS: In total, 265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L were enrolled. Participants had BMIs of 20.0-34.2 kg/m2. IR, FPIS, SPIS, and GE were estimated using our previously developed equations. Pearson correlation analysis was conducted to assess the correlations between the four diabetogenesis factors and BMI. A general linear model was used to determine the differences in the percentage of change among the four factor slopes against BMI. RESULTS: Significant correlations were observed between BMI and FPIS, SPIS, IR, and GE in both women and men, which were higher than those reported previously. In men, BMI had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in women, the order was slightly different: IR, followed by FPIS, SPIS, and GE. Significant differences were observed among all these slopes, except for the slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p = 0.258). CONCLUSIONS: The contribution of obesity to all diabetes factors, except GE, was higher than that reported previously. BMI had the most profound effect on insulin secretion in men and on IR in women in this 60-year-old cohort, suggesting that lifestyle modifications for obesity reduction in women remain the most important method for improving glucose metabolism and preventing future type 2 diabetes mellitus.

High normotension is associated with future metabolic syndrome but not cardiovascular disease: A 10-year longitudinal study.

Hypertension and prehypertension can increase the risk of developing cardiovascular disease (CVD) and diabetes. However, whether the harmful effects of high blood pressure (BP) are also seen with high normotension remains unknown. This 10-year longitudinal follow-up study aimed to investigate the relationships among normal-range BP, metabolic syndrome (MetS), and CVD.A total of 9133 nonmedicated normotensive participants, 4634 males and 4499 females, aged 60 years or older were enrolled in a standard health examination program at 2 academic hospitals and a health screening center in Taiwan. The study subjects were divided into 3 groups according to their BP. The systolic BP (SBP) ranges of groups 1, 2, and 3 were 91 to 100, 101 to 110, and 111 to 119 mmHg, whereas the diastolic BP (DBP) ranges of groups 1, 2, and 3 were 51 to 60, 61 to 70, and 71 to 79 mmHg, respectively.In the SBP3 group, both sexes had a higher odds ratio (OR) for having MetS or abnormal MetS components, except for triglycerides. Females in the DBP3 group had a higher OR for having MetS at baseline. After the follow-up period, the SBP3 group had a significantly higher hazard ratio (HR) for developing MetS. Males in the DBP3 group and females in the DBP2 and DBP3 groups had a significantly higher HR for developing MetS. Neither the SBP3 group nor the DBP3 group had a higher HR for developing nonfatal CVD. In the Kaplan-Meier analysis, SBP and DBP in both sexes showed statistical significance as predictors of MetS, but not of nonfatal CVD.High normotensive elderly individuals have an elevated risk of developing MetS at baseline and within 10 years of follow-up, but they are not at increased risk of CVD. Preventive interventions, such as life-style modification, should be offered early even to the apparently healthy elderly.

The Acquisition of Orthographic Knowledge: Evidence from the Lexicality Effects on N400.

This study aimed to understand how reading ability shapes the lexicality effects on N400. Fifty-three typical developing children from the second to the sixth grades were asked to perform the pronounceability judgment task on a set of Chinese real characters (RC), pseudocharacters (PC) and non-characters (NC), as ERPs were recorded. The cluster-based permutation analysis revealed that children with low- to medium-reading ability showed greater negativity to NCs than to RCs and PCs in frontal sites from 300 to 450 ms, while children with high ability group showed a greater positivity to NCs than both RCs and PCs at central to posterior sites. Furthermore, the linear mixed model (LMM) analysis was applied to investigate the relationship between lexicality effects on N400 and reading-related behavioral assessments on a set of standardized tests (including character recognition, vocabulary size, phonological awareness, and working memory). The results found that in children with lower reading ability, the N400 elicited by NCs becomes more negative in the frontal sites. For children with higher reading ability, the N400 elicited by NCs became more positive than that elicited by RCs or PCs in the posterior sites. These findings demonstrate the developmental changes in the lexicality effects on N400 as children become more advanced readers and suggested that the lexicality effects on N400 can serve as neural markers for the evaluation of orthographic proficiency in reading development.

Identification of Impaired Second-Phase Insulin Secretion in Various Degrees of Glucose Tolerance in a Chinese Population.

AIM: Impaired insulin sensitivity and insulin secretion (ISEC) are major pathophysiologies of type 2 diabetes (T2DM). ISEC has two phases: the first and second phases (second ISEC). In this study, we derived equations to identify patients with second ISEC deficiency (ISEC-D). METHODS: Data from 96 patients, namely 19 with a normal fasting plasma glucose (FPG) level, 21 with prediabetes, and 56 with T2DM, were enrolled. They underwent a modified low-dose graded glucose infusion test, which was originally proposed by Polonsky et al. The test results were interpreted as the slopes of the changes of plasma insulin against the glucose levels, which were considered second ISEC. Patients with the lowest quartile of the slopes were defined as having ISEC-D. We built three models: Model 0: FPG, Model 1: FPG + waist circumference, and Model 2: Model 1 + fasting plasma insulin. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models. RESULTS: Among the metabolic syndrome components, FPG had the largest aROC curve (78.2%). Although aROC curves of Models 1 and 2 (85.2% and 91.5%, respectively) were higher than the aROC curve of FPG, no difference was observed between Models 1 and 0. By contrast, the aROC curve of Model 2 was higher compared with Model 1. CONCLUSIONS: FPG showed the largest aROC curve. Model 2 had the highest predictive power, which could identify patients with ISEC-D with a sensitivity and specificity of 94.3% and 82.6%, respectively. These two models could be conveniently used in daily practice.

Depression as the Primary Cause of Insomnia and Excessive Daytime Sleepiness in a Family with Multiple Cases of Spinocerebellar Ataxia.

ABSTRACT: Spinocerebellar ataxia (SCA) is a hereditary disease characterized by central nervous system-related motor dysfunctions. Sleep disorders and frequent non-motor manifestations are commonly comorbid with SCA. To elucidate this relationship, we present three cases in a family that included multiple SCA type 2 patients with various sleep disorders. Complete physical examination, and genetic and imaging studies were performed. Anti-parkinsonism medications were prescribed after neurological examination. Clonazepam and/or quetiapine were administered for sleep disorders but failed to resolve insomnia and excessive daytime sleepiness (EDS). Based on DSM-5 criteria, all cases were diagnosed with depression. After treatment with serotonin-norepinephrine reuptake inhibitors and noradrenergic and specific serotonergic antidepressants, symptoms of insomnia and EDS, which are strongly associated with depression in SCA type 2 patients, improved significantly. It is crucial to recognize insomnia and EDS in neurodegenerative diseases, not only for earlier diagnosis, but also to improve quality of life.