• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.79-89
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• 2012

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

• Anxiety and mood
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• v.2 no.2
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• pp.101-107
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• 2006

Object : Since autonomic nerve system dysfunction was known as the mechanism of panic disorder, many researchers used heart rate variability (HRV) as means of measuring autonomic nerve function of patients with panic disorder. We aimed to examine the effect of paroxetine medication for 3 months on symptom improvement and change of heart rate variability of the patients with panic disorder. Methods : The subjects were patients with panic disorder who visited the psychiatric outpatient clinic of Samsung Medical Center in Seoul. We included panic disorder patients who were aged from 20 to 50 and in normal BMI range (from 18 to 30) to minimize the effect of age and weight on HRV data. We excluded the patients with EKG abnormalities, hypertension or other major psychiatric disorders. They took 20-40 mg paroxetine medication a day for 3 months. Alprazolam was used only during the first month to control the acute panic symptoms and was tapered off after that. We measured the acute panic inventory (API), Hamilton rating scale for anxiety and depression (HAM-A & HAM-D), Spielberger state-trait anxiety inventory (STAIS, STAIT), and Beck depression inventory (BDI) in order to assess clinical improvement of the patients. And we measured time and frequency domain HRV in the resting, standing and cognitive stress states to assess the change of HRV. All measurements were done before and after paroxetine treatment. Result : After paroxetine medication, patients showed significant improvement in all psychiatric scales. In time domain of HRV, standard deviations of all R-R intervals (SDNN) were significantly increased in all states. In frequency domain of HRV, the ratio of high frequency to total power (HF/TP) in the standing state was significantly increased. Conclusion : After 3 months paroxetine medication, panic disorder patients showed significant clinical improvement and change in HRV data such as SDNN in all states and HF/TP ratio in the standing state. This result suggests that paroxetine medication is effective for the improvement of autonomic nerve system dysfunction in panic disorder patients.

• Safety and Health at Work
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• v.3 no.4
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• pp.257-267
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• 2012

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

• Molecules and Cells
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• v.37 no.11
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• BMB Reports
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• v.57 no.6
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• pp.281-286
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• 2024

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

• The Journal of Korean society of community based occupational therapy
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• v.2 no.1
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• pp.49-63
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• 2012

Objective : The purpose of study was to verify the clinical effect of a Korean Computer-based cognitive rehabilitation program(called CoTras) for recovering the visual perception function and ADL in stroke. Methods : A CBCRT was applied to 14 Stoke patients who rehabilitation professional medical treatment hospital. All participant were evaluated with four standardized assessment tolls(Motor-Free Visual Perception Test; MVPT, Korean version of Mini-Mental State Examination; MMSE-K, Assesment of Motor and Process Skills: AMPS) before and after the planned computer based cognitive rehabilitation sessions. Results : A significant effect was confirmed (p<.05) from the CBCRT which visual perception function. By each entry comparative result, visual memory, figure ground, visual close, spatial relation, visual discrimination, were the order of treatment. Neither was found any significant effect in improving process skills from AMPS. Conclusion : These results indicate that CoTras have effects on improving visual perception and ADL performance in stroke patients. Will be able to present with the fundamental data CoTras will be able to contribute to increase visual perception function & ADL performance to the stroke patient who has visual perception dysfunction.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• Journal of the Korean Applied Science and Technology
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• v.41 no.1
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• pp.58-68
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• 2024

The purpose of this study was to investigate the effects of treadmill exercise treadmill exercise (TE) and environmental enrichment (EE) interventions on cognitive function, muscle function, and the expression of tight junction proteins in an Alzheimer's disease (AD) animal model. To create the AD animal model, aluminum chloride (AlCl₃) was administered for 90 days (40mg/kg/day), while simultaneously exposing the animals to TE (10-12m/min, 40-60min/day) or EE. The results showed that cognitive impairment and muscle dysfunction induced by AlCl₃ administration were alleviated by TE and EE. Furthermore, TE and EE reduced the increased expression of β-amyloid(Aβ), alpha-synuclein, and tumor necrosis factor-α (TNF-α) proteins observed in AD pathology. Additionally, TE and EE significantly increased the expression of decreased adhesive adjacent proteins (Occludin, Claudin-5, and ZO-1) induced by AlCl₃ administration. Lastly, correlation analysis between Aβ protein and tight junction proteins showed negative correlations (Occludin: r=-0.853, p=0.001; Claudin-5: r=-0.352, p=0.915; ZO-1: r=-0.424, p=0.0390). In conclusion, TE or EE interventions are considered effective exercise methods that partially alleviate pathological features of AD, improving cognitive and muscle function.

• Sleep Medicine and Psychophysiology
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• v.20 no.1
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• pp.15-21
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• 2013

Objectives: Cognitive impairment in restless legs syndrome (RLS) patients can be affected by sleep deprivation, anxiety and depression, which are common in RLS. The objective of this study is to investigate relationship between cognitive impairment and RLS in the non-medicated Korean elderly with controlling for psychiatric conditions. Method: The study sample for this study comprised 25 non-medicated Korean elderly RLS patients and 50 age-, sex-, and education- matched controls. All subjects were evaluated with comprehensive cognitive function assessment tools- including the Korean version of Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K), severe cognitive impairment rating scale (SCIRS), frontal assessment battery (FAB), and clock drawing test (CLOX). Sleep quality and depression were also assessed with Pittsburgh sleep quality index (PSQI) and geriatric depression scale (GDS). Results: PSQI and GDS score showed no difference between RLS and control group. There was no significant difference between two groups in nearly all the cognitive function except in constructional recognition test, in which subjects with RLS showed lower performance than control group (t=-2.384, p=0.02). Subjects with depression ($GDS{\geq}10$) showed significant cognitive impairment compared to control in verbal fluency, Korean version of Mini Mental Status Examination in the CERAD-K (MMSE-KC), word list memory, trail making test, and frontal assessment battery (FAB). In contrast, no difference was observed between subjects who have low sleep quality (PSQI>5) and control group. Conclusions: At the exclusion of the impact of insomnia and depression, cognitive function was found to be relatively preserved in RLS patients compared to control. Impairment of visual recognition in RLS patients can be explained in terms of dopaminergic dysfunction in RLS.

• Journal of Life Science
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• v.30 no.3
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• pp.250-259
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• 2020

Diabetes is a well-known risk factor for dementia and cognitive impairment. Diabetic polyneuropathy (DPN) is the most prevalent microvascular complication in type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the relation between diabetic peripheral polyneuropathy and cognitive factors in T2DM patients. Retrospective chart review of type 2 diabetic patients with results of a nerve conduction study (NCS) and a neurocognitive study. A total of 19 patients were included. DPN was defined using data from a nerve conduction study: a score of less than 24 in the Korean version of the Mini-Mental State Examination (K-MMSE) was considered as an indicator of cognitive impairment (CI). The mean age of the 19 patients was 71.6±5.0 years. The mean duration of diabetes was 8.4±9.1 years, and the mean HbA1c level was 8.1±1.8%. DPN was present in 7 of the 19 patients. Based on the K-MMSE score, CI was diagnosed in eight patients. The mean K-MMSE scores and the prevalence of CI was not different between the groups with and without DPN. There was no significant difference in DPN prevalence between the groups with and without CI. Education was significantly correlated with cognitive factors. Only the digit span-forward among the cognitive factors showed a significant negative correlation with nerve conduction velocity. In conclusion, the longer education period was associated with higher cognitive function and no significant correlation was observed between diabetic peripheral neuropathy and cognitive dysfunction in type 2 diabetic patients. Further prospective research is needed in the future.