This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) (P < 0.05). In the Y-maze test, the spontaneous alternation in al HLJG0711-treated groups was significantly increased compared with that in SPL-G (P < 0.05). In the Morris water maze test, the escape latency and time spent in the target quadrant in all HLJG0701-treated groups were significantly decreased and increased, respectively, compared with those in SPL-G (P < 0.05). In addition, the brain-derived neurotrophic factor level in groups treated with HLJG0701 300 and 600 mg/kg body weight was significantly increased compared with that in SPL-G (P < 0.05). These results suggest that the HLJG0701 may protect against memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.
Acetylcholine ; Acetylcholinesterase ; Animals ; Body Weight ; Brain-Derived Neurotrophic Factor ; Ginsenosides ; Humans ; Learning ; Male ; Memory Disorders* ; Memory* ; Memory, Short-Term ; Mice* ; Mice, Inbred ICR ; Models, Animal ; Panax* ; Scopolamine Hydrobromide ; United Nations ; Water

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.
Acetylcholine ; Acetylcholinesterase ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Blotting, Western ; Brain ; Cholesterol ; Cognition Disorders* ; Cyclic AMP Response Element-Binding Protein ; Dementia* ; Drug Therapy ; Ethanol ; Extracellular Signal-Regulated MAP Kinases ; Functional Food ; Hippocampus ; Immunohistochemistry ; Laminaria* ; Memory ; Mice* ; Neurodegenerative Diseases ; Neuronal Plasticity* ; Neuroprotective Agents ; Receptors, Muscarinic ; Scopolamine Hydrobromide ; Triglycerides ; United Nations ; Water

Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.
Acetylcholinesterase ; Animals ; Brain Diseases ; Cognition Disorders* ; Cytokines ; DNA Nucleotidylexotransferase ; Humans ; Learning ; Memory ; Mice ; Mice, Inbred ICR ; Neurons ; Oxidative Stress ; Scopolamine Hydrobromide ; Superoxide Dismutase ; United Nations ; Water

Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. Due to this ambiguity of distinction between the DIP and schizophrenia, the DIP animal model has been frequently used as the schizophrenia animal model. However, although the symptoms may be the same, its causes are clearly different in that DIP is acquired and schizophrenia is heritable. Therefore, in this review, we cover several DIP models such as of amphetamine, PCP/ketamine, scopolamine, and LSD, and then we also address three schizophrenia models through a genetic approach with a new perspective that distinguishes DIP from schizophrenia.
Amphetamine ; Anhedonia ; Classification ; Executive Function ; Hallucinations ; Humans ; Lysergic Acid Diethylamide ; Models, Animal ; Psychotic Disorders* ; Schizophrenia ; Scopolamine Hydrobromide ; Substance-Related Disorders*

4-Hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are natural phenolic compounds, which present in many plants and have diverse biological properties. In this study, we examined effects of vanillin and 4-HBA on learning and memory function, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a mouse model of scopolamine-induced amnesia. Scopolamine (SCO; 1 mg/kg/day, intraperitoneally), vanillin, and 4-HBA (40 mg/kg/day, orally) were administered for 28 days. Treatment with scopolamine alone impaired learning and memory function in the Morris water maze and passive avoidance tests, in addition, the treatment significantly reduced cell proliferation and neuroblast differentiation in the dentate gyrus, which were examined by immunohistochemistry for Ki-67 (a classic marker for cell proliferation) and doublecortin (a marker for neuroblasts). However, treatment with vanillin or 4-HBA significantly attenuated SCO-induced learning and memory impairment as well as the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. These results indicate that vanillin and 4-HBA may be helpful in improving cognitive function and in increasing endogenous neuronal proliferation in the brain.
Amnesia* ; Animals ; Brain ; Cell Proliferation* ; Cognition ; Cognition Disorders* ; Dentate Gyrus* ; Hippocampus ; Immunohistochemistry ; Learning ; Memory ; Mice* ; Neurogenesis ; Neurons ; Phenol ; Scopolamine Hydrobromide ; Water

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal β-amyloid (Aβ) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine·HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a Aβ₁₋₄₂-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the Aβ₁₋₄₂-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of Aβ-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.
Acetylcholine ; Alzheimer Disease ; Amnesia ; Animals ; Brain ; Calcium ; Cell Survival ; Cognition Disorders ; Cognition* ; Depression ; Dizocilpine Maleate ; Learning ; Memory ; Models, Animal* ; Neurodegenerative Diseases ; Neurons ; Rats* ; Reactive Oxygen Species ; Scopolamine Hydrobromide ; Spatial Memory ; Stroke ; Water

Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies (“classic jackhammer esophagus,” n=7) and the other with hypercontractility and short distal latencies (“spastic jackhammer esophagus,” n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, “classic jackhammer esophagus” and “spastic jackhammer esophagus,” to distinguish the two types.
Classification ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Deglutition Disorders ; Esophageal Motility Disorders ; Esophagus* ; Humans ; Muscle Spasticity* ; Muscle, Smooth ; Scopolamine Hydrobromide

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.
Acetic Acid ; Acetylcholinesterase ; Alzheimer Disease ; Animals ; Brain-Derived Neurotrophic Factor ; Carbuncle ; Dianthus* ; Hippocampus ; Learning ; Memory* ; Mice* ; Scopolamine Hydrobromide ; Up-Regulation ; Urethritis ; Water

No abstract available.
Depression* ; Isoflurane* ; Nitrous Oxide* ; Scopolamine Hydrobromide*

Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0-97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.
Clozapine ; Humans ; Schizophrenia ; Scopolamine Hydrobromide* ; Sialorrhea* ; Visual Analog Scale