2.Stress and Sleep Disorder.
Kuem Sun HAN ; Lin KIM ; Insop SHIM
Experimental Neurobiology 2012;21(4):141-150
The purpose of this study was to review potential, physiological, hormonal and neuronal mechanisms that may mediate the sleep changes. This paper investigates the literatures regarding the activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems during sleep in order to identify relations between stress and sleep disorder and the treatment of stress-induced insomnia. Sleep and wakefulness are regulated by the aminergic, cholinergic brainstem and hypothalamic systems. Activation of the HPA and/or the sympathetic nervous systems results in wakefulness and these hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol or corticosterone, noradrenaline, and adrenaline, are associated with attention and arousal. Stress-related insomnia leads to a vicious circle by activating the HPA system. An awareness of the close interaction between sleep and stress systems is emerging and the hypothalamus is now recognized as a key center for sleep regulation, with hypothalamic neurontransmitter systems providing the framework for therapeutic advances. An updated understanding of these systems may allow researchers to elucidate neural mechanisms of sleep disorder and to develop effective intervention for sleep disorder.
Adrenocorticotropic Hormone
;
Arousal
;
Brain Stem
;
Corticosterone
;
Corticotropin-Releasing Hormone
;
Epinephrine
;
Hydrocortisone
;
Hypothalamus
;
Neurons
;
Norepinephrine
;
Sleep Initiation and Maintenance Disorders
;
Sympathetic Nervous System
;
Wakefulness
;
Axis, Cervical Vertebra
;
Sleep Wake Disorders
3.The Protective Effect of Black Ginseng Against Transient Focal Ischemia-induced Neuronal Damage in Rats.
Hyun Jung PARK ; Hyun Soo SHIM ; Kyung Soo KIM ; Insop SHIM
The Korean Journal of Physiology and Pharmacology 2011;15(6):333-338
Black ginseng (BG) has been widely used as herbal treatment for improving physiological function. In order to investigate the neuroprotective action of this herbal medicine, we examined the influence of BG on the learning and memory of rats using the Morris water maze, and we studied the effects of BG on the central cholinergic system and neural nitric oxide synthesis in the hippocampus of rats with neuronal and cognitive impairment. After middle cerebral artery occlusion was applied for 2h, the rats were administered BG (100 or 400 mgkg(-1), p.o.) daily for 2 weeks, followed by training and performance of the Morris water maze test. The rats with ischemic insults showed impaired learning and memory on the tasks. Treatment with BG produced improvement in the escape latency to find the platform. Further, the BG groups showed a reduced loss of cholinergic immunoreactivity and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in the hippocampus compared to that of the ISC group. These results demonstrated that BG has a protective effect against ischemia-induced neuronal and cognitive impairment. Our results suggest that BG might be useful for the treatment of vascular dementia.
Animals
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Dementia, Vascular
;
Herbal Medicine
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Hippocampus
;
Infarction, Middle Cerebral Artery
;
Learning
;
Memory
;
NAD
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Neurons
;
Nitric Oxide
;
Panax
;
Rats
;
United Nations
4.L-Tetrahydropalmatine Ameliorates Development of Anxiety and Depression-Related Symptoms Induced by Single Prolonged Stress in Rats.
Bombi LEE ; Bongjun SUR ; Mijung YEOM ; Insop SHIM ; Hyejung LEE ; Dae Hyun HAHM
Biomolecules & Therapeutics 2014;22(3):213-222
Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitary-adrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.
Animals
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Anxiety*
;
Arm
;
Axis, Cervical Vertebra
;
Depression
;
Grooming
;
Head
;
Humans
;
Hypothalamus
;
Male
;
Models, Animal
;
Neuropeptide Y
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Physical Exertion
;
Rats*
;
Risk Assessment
;
Stress Disorders, Post-Traumatic
5.The Central and Peripheral Production of Pro-inflammatory Cytokine, IL-1b after Immune and Stress Stimulation in Rats.
Eun Yee JUNG ; Kyung Soo KIM ; Insop SHIM
Experimental Neurobiology 2008;17(2):47-54
Interleukin-1beta (IL-1beta), one of the pro-inflammatory cytokines, acts as an endogenous pyrogen and is an important mediator of behavioral and physiological responses to immune stimulation as well as exposure to stressors. The objective of the present study was to examine the pattern of central or peripheral IL-1beta response to lipopolysaccharide (LPS) or exposure to the foot shock stress (FS) in rats. After treatment of LPS (100microgram/kg) or exposure to the FS [ten times (0.8 mA) foot shocks for 5 sec each and 90 sec interval], body temperature and IL-1beta levels in plasma, spleen and brain were measured. Both LPS and FS stimuli elicited increased body temperature but showed different patterns of peripheral IL-1beta levels. LPS produced a widespread increase in IL-1beta levels in the plasma, spleen and brain, whereas FS produced a significant increase in IL-1beta levels only in the brain regions but not in plasma and spleen. The present study suggests that IL-1beta is, centrally or peripherally in different patterns, regulated by immune stimulation or exposure to stressors and IL-1beta plays an important role in mediating responses of sickness-like behaviors induced by immune stimuli or stressors.
Animals
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Body Temperature
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Brain
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Cytokines
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Foot
;
Interleukin-1
;
Interleukin-1beta
;
Negotiating
;
Plasma
;
Rats
;
Shock
;
Spleen
6.Differential DAergic Control of D1 and D2 Receptor Agonist Over Locomotor Activity and GABA Level in the Striatum.
Experimental Neurobiology 2011;20(3):153-157
The basal ganglia, a group of nuclei, are associated with a variety of functions, including motor control. The striatum, which is the major input station of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. The striatum is made up 96% of medium spiny neurons which are GABAergic cells. GABAergic cells are known to contain DA receptors which divide into two main branches- the D1 receptor (D1R)-expressing direct pathway and the D2 receptor (D2R)-expressing indirect pathway. The role of these two efferent pathways has not been clear in control of motor behaviors. To establish the influence of the different DA subtypes on GABAergic systems in the striatum, D1 selective receptor agonist (SKF 38393) and D2 selective receptor agonist (Quinpirole) were administered to mice. SKF 38393 and quinpirole were administered intraperitoneally in a volume of 0, 1, 5, 10 (mg/kg) and motor activity was assessed for 60 min immediately after the injection of DA agonists. Mice were sacrificed after behavioral test and the striatum in the brain were dissected for analysis of GABA level with HPLC. Both SKF 38393 and quinpirole dose-dependently increased locomotor activity but, GABA level in the striatum was clearly different in two agonists. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal GABAergic motor behaviors.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
;
Animals
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Basal Ganglia
;
Brain
;
Chromatography, High Pressure Liquid
;
Efferent Pathways
;
gamma-Aminobutyric Acid
;
Mice
;
Motor Activity
;
Neurons
;
Quinpirole
;
Substantia Nigra
7.The Effects of Astragalus Membranaceus on Repeated Restraint Stress-induced Biochemical and Behavioral Responses.
Hyun Jung PARK ; Hyun Young KIM ; Kun Ho YOON ; Kyung Soo KIM ; Insop SHIM
The Korean Journal of Physiology and Pharmacology 2009;13(4):315-319
Astragalus Membranaceus (AM) is a useful Korean herb that has been clinically prescribed for stress-related illness. The objective of the present study was to examine the anti-stress effects of AM on repeated stress-induced alterations of anxiety, learning and memory in rats. Restraint stress was administered for 14 days (2h/day) and AM (400mg/kg) given by oral administration, in the AM group, for the same period. Starting on the eighth day, the rats were tested for spatial memory on the Morris water maze test (MW) and for anxiety on the elevated plus maze (EPM). Changes of expression on immunohistochemistry were studied for cholineacetyl transferase (ChAT) and tyrosine hydroxylase (TH) in the brain. The results showed that the rats treated with AM had significantly reduced stress-induced deficits on learning and memory on the spatial memory tasks. In addition, the ChAT immunoreactivities were increased. In the EPM, treatment with AM increased the time spent in the open arms (p<0.001) compared to the control group. In addition, AM treatment also normalized increases of TH expression in the LC (p<0.001). In conclusion, administration of AM improved spatial learning and memory and reduced stress-induced anxiety. Thus, the present results suggest that AM is able to recover behavioral and neurochemical impairments induced by stress.
Administration, Oral
;
Animals
;
Anxiety
;
Arm
;
Astragalus membranaceus
;
Brain
;
Immunohistochemistry
;
Learning
;
Memory
;
Rats
;
Transferases
;
Tyrosine 3-Monooxygenase
8.Tetramethylpyrazine reverses anxiety-like behaviors in a rat model of post-traumatic stress disorder.
Bombi LEE ; Insop SHIM ; Hyejung LEE ; Dae Hyun HAHM
The Korean Journal of Physiology and Pharmacology 2018;22(5):525-538
Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.
Animals
;
Anxiety
;
Arm
;
Freezing
;
Grooming
;
Hippocampus
;
Humans
;
Models, Animal*
;
Prefrontal Cortex
;
Rats*
;
RNA, Messenger
;
Serotonin
;
Stress Disorders, Post-Traumatic*
;
Thymidine Monophosphate
;
Tryptophan
9.Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder.
Bombi LEE ; Insop SHIM ; Hyejung LEE ; Dae Hyun HAHM
The Korean Journal of Physiology and Pharmacology 2018;22(2):183-192
Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.
Animals
;
Anxiety*
;
Arm
;
Berberine*
;
Depression
;
Dopamine*
;
Grooming
;
Hippocampus
;
Humans
;
Rats*
;
RNA, Messenger
;
Stress Disorders, Post-Traumatic*
;
Tyrosine 3-Monooxygenase
;
Vesicular Monoamine Transport Proteins
10.The Effects of Puerariae Flos on Stress-induced Deficits of Learning and Memory in Ovariectomized Female Rats.
Hyun Jung PARK ; Seung Moo HAN ; Won Ju YOON ; Kyung Soo KIM ; Insop SHIM
The Korean Journal of Physiology and Pharmacology 2009;13(2):85-89
Puerariae flos (PF) is a traditional oriental medicinal plant and has clinically been prescribed for a long time. The purpose of the present study was to examine the effect of PF on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) test in ovariectomized (OVX) female rats. The changes in the reactivity of the cholinergic system were assessed by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral testing. The female rats were randomly divided into four groups: the nonoperated and nonstressed group (normal), the sham-operated and stressed group (control), the ovariectomized and stressed group (OS), and the ovariectomized, stressed and PF treated group (OSF). Rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and PF (400 mg/kg, p.o.) was administered 30 min before IMO stress. Results showed that treatments with PF caused significant reversals of the stress-induced deficits in learning and memory on a spatial memory task, and also increased the ChAT immunoreactivities. In conclusion, administration of PF improved spatial learning and memory in OVX rats, and PF may be useful for the treatment of postmenopausal-related dementia.
Animals
;
Choline O-Acetyltransferase
;
Female
;
Hippocampus
;
Humans
;
Immobilization
;
Learning
;
Memory
;
Neurons
;
Ovariectomy
;
Plants, Medicinal
;
Pueraria
;
Rats