Chan Young Lee

Purpose: Serotonin (5-HT) release in the hippocampus is modulated by N-methyl-D-aspartate (NMDA) receptor activity, particularly under hypoxic conditions, but the roles of other neurotransmitter systems remain unclear. This study examined how several neurotransmitters affect spontaneous 5-HT release in rat hippocampal slices and whether these effects are direct or interneuron-mediated.Methods: Rat hippocampal slices (400 μm) were preloaded with [3H]5-HT and superfused with oxygenated buffer. Acetylcholine (ACh), norepinephrine (NE), dopamine (DA), NMDA, γ-aminobutyric acid (GABA), glycine, or neuropeptide Y (NPY) were applied for 20 minutes, and [3H]5-HT release was measured in 10-minute fractions. Tetrodotoxin (TTX) was used in parallel experiments to block action potential-dependent neurotransmission.Results: In control slices, spontaneous [3H]5-HT release reached a stable baseline after approximately 50 minutes of superfusion. ACh (10-5M), GABA (10-5M), glycine (10-5M), and NPY (10-6M) did not significantly affect 5-HT release relative to control. In contrast, NE (10-5M) and DA (10-5M) significantly increased 5-HT release (peaking at ~15%–37% above baseline, P<0.05), and these effects persisted in the presence of TTX, suggesting a direct action on serotonergic terminals. NMDA (10-4M) also transiently enhanced 5-HT release (~22% above baseline, P<0.05), but this effect was completely abolished by TTX, indicating reliance on interneuronal activity.Conclusions: Hippocampal 5-HT release is differentially regulated by neurotransmitter systems: NE and DA act directly at serotonergic terminals, whereas NMDA’s effect requires interneuronal activity. These findings highlight complex neurochemical interactions that may underlie serotonergic modulation in neuropsychiatric disorders.

Purpose: Antidepressants can induce urinary retention, difficulty in voiding, and delayed micturition, effects thought to result from detrusor relaxation and increased urethral sphincter tone mediated by enhanced central serotonergic activity. However, direct measurements of brain serotonin following antidepressant treatment remain limited. The relative risk of voiding difficulty across different antidepressant classes may help guide individualized antidepressant selection. This study aimed to assess changes in hypothalamic serotonin levels after administration of various antidepressants using an animal microdialysis model.Methods: Male Sprague-Dawley rats (280–330 g) were randomly assigned to 5 groups (n=8 per group) and received intraperitoneal injections of saline, clomipramine, fluoxetine, sertraline, or paroxetine (10 mg/kg). A microdialysis probe was stereotaxically implanted in the hypothalamus and perfused with artificial cerebrospinal fluid. Dialysate samples were collected every 20 minutes in freely moving animals and analyzed for serotonin levels via high-performance liquid chromatography with electrochemical detection.Results: All tested antidepressants significantly elevated extracellular serotonin in the hypothalamus compared to baseline. The magnitude of increase was greatest with clomipramine, followed by sertraline, paroxetine, and fluoxetine. Peak serotonin levels were observed at 120 minutes post-administration for clomipramine and sertraline, whereas paroxetine and fluoxetine peaked at 240 minutes.Conclusions: Antidepressant treatment increases hypothalamic serotonin, with clomipramine and sertraline producing the most pronounced effects. Considering that clomipramine and paroxetine combine high serotonergic elevation with notable anticholinergic activity, these drugs may pose a higher risk of voiding difficulties than fluoxetine or sertraline. This study focused on characterizing central serotonergic responses to antidepressant administration as a neurochemical endpoint. The relative risk of voiding difficulty across different antidepressant classes may help guide individualized antidepressant selection. Clinicians should exercise caution when prescribing these agents to elderly patients, individuals with benign prostatic hyperplasia, or those receiving concurrent anticholinergic medications.

Lee CY, et al. J Clin Neurol. 2026 Sep;22(5):633-634. https://doi.org/10.3988/jcn.2026.0368

Lee CY, et al. J Clin Neurol. 2026 ;22:e32. https://doi.org/10.3988/jcn.2025.0548

Objective The Huntington’s Disease Quality of Life Battery for Carers (HDQoL-C) is used to evaluate caregiver quality of life. This study aimed to develop and validate the Korean version of the HDQoL-C (K-HDQoL-C) to assess the burden on Korean caregivers of Huntington’s disease (HD) patients.Methods A total of 19 HD caregivers (7 females, mean age 55.4±14.6 years) participated in this study. The K-HDQoL-C, a translation of the English version, consisted of demographic information, caring aspects, life satisfaction, and feelings about life. It was administered twice, 2 weeks apart. Internal consistency was evaluated using Cronbach’s α, and test-retest reliability was assessed with intraclass correlation coefficients. The relationship with the Zarit Burden Interview-12 (ZBI-12) was analyzed.Results The internal consistencies of the K-HDQoL-C were 0.771 (part 2), 0.938 (part 3), and 0.891 (part 4). The test-retest reliability ranged from 0.908 to 0.936. Part 3 was negatively correlated with the ZBI-12, and part 4 was positively correlated with the ZBI-12 (r=-0.780, 0.923; p<0.001).Conclusion The K-HDQoL-C effectively evaluates the challenges faced by HD caregivers, particularly in terms of care aspects and life satisfaction.

Highly active antiretroviral therapy improves immune function in human immunodeficiency virus patients but can lead to progressive multifocal leukoencephalopathy (PML) due to immune reconstitution inflammatory syndrome (IRIS). PML, caused by John Cunningham (JC) virus, affects the central nervous system in immunocompromised individuals. Despite the negative result for JC virus in the cerebrospinal fluid test, we report a rare case of PML-IRIS that was diagnosed based on clinical presentation and brain magnetic resonance imaging findings and showed improvement with steroid therapy.

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson’s disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11–2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.

The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson’s disease (PD) found in pathological studies is the “rostrocaudal gradient,” which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.

Objective This is the first prospective cohort study of Huntington’s disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers.Methods From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups.Results Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38–65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson–Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers’ demographics, blood relation, and marital and social status did not affect the burden significantly.Conclusion HD patients’ neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Background and objectives This study aimed to determine the possibility as a biomarker and identify predictors of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of patients with Parkinson’s disease (PD). Methods The frequency of AS accumulation in the GI tract was compared between patients with PD (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). Clinical characteristics were compared between patients with positive (AS+) and negative (AS−) AS accumulation. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of patients with PD. Results The frequency of AS accumulation was significantly higher in patients with PD (75.3%) than in controls (8.5%, p-value < 0.001). However, when the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in patients with PD. The duration from symptom onset to surgery was significantly longer in patients with PD and AS+ (4.9 ± 4.9 years) than in AS– (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and surgical site independently predicted the presence of AS accumulation in the GI tract of patients with PD. Conclusions The results suggest that the stomach is the optimal location for identifying pathological biomarkers using AS accumulation in the GI tract. Our study suggests PD-related AS accumulation in the GI tract follows temporally increasing but spatially static progression pattern.