• Title/Summary/Keyword: Neurotransmitters

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Exploring amygdala structural changes and signaling pathways in postmortem brains: consequences of long-term methamphetamine addiction

  • Zahra Azimzadeh;Samareh Omidvari;Somayeh Niknazar;Saeed Vafaei-Nezhad;Navid Ahmady Roozbahany;Mohammad-Amin Abdollahifar;Foozhan Tahmasebinia;Gholam-Reza Mahmoudiasl;Hojjat Allah Abbaszadeh;Shahram Darabi
    • Anatomy and Cell Biology
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    • v.57 no.1
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    • pp.70-84
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    • 2024
  • Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

Trends in Antidote Technologies for Nerve Agents (신경작용제 해독 기술 동향)

  • Sungyiel Kim;Jinkwang Jeong;Dongwook Kim;Seungyul Hwang;Yoonje Cho;Yeongwook Yoon;Taein Ryu;Keunhong Jeong
    • Applied Chemistry for Engineering
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    • v.35 no.4
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    • pp.284-295
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    • 2024
  • Chemical agents are classified according to their mechanism of toxicity into categories such as nerve agents, choking agents, blood agents, blister agents, etc. Among them, nerve agents cause toxic symptoms by binding with acetylcholinesterase (AChE) in the body, which breaks down neurotransmitters, thus disrupting the autonomic nervous system. In severe cases, this can lead to death, making it a critical chemical agent. Therefore, once it has penetrated into the human body, it is important to detoxify it swiftly. Antidotes used for detoxification include chemical medicines such as pretreatment agents, post-treatment agents, anticonvulsants, and bioscavengers. This review will address the uses, forms, components, and principles of detoxification of nerve agent antidotes and the association with bioscavengers.

Cognitive Improvement Effects of Krill Oil in a Scopolamine-induced Mice Model (Scopolamine 유도 인지 저하 마우스 모델에서 크릴 오일의 인지 개선 효과)

  • Hye-Min Seol;Jeong-Ah Lee;Mi-Sun Hwang;Sang-Hoon Park;Hyeong-Soo Kim
    • Journal of Life Science
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    • v.34 no.7
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    • pp.509-519
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    • 2024
  • A previous study showed that krill oil improved recognition and memory through anti-oxidative effects in an amyloid β model, but the authors noted that further investigations are necessary of alterations to neurotransmitters' states and of serum lipid profile improvements related to serum lipid peroxidation. Accordingly, in this study, ICR mice were pre-treated intraperitoneally with scopolamine prior to induced neurotransmission impairment, and the effects of krill oil provision on their capabilities of cognition were tested by performing a passive avoidance test (PAT), water maze test (WMT), and novel object recognition test. Then, parameters including the acetylcholine (ACh) concentration, acetylcholinesterase activity (AChE), lipid peroxidation, serum lipid levels, and nerve cell proliferation were investigated. The results showed that krill oil improved the mice's abilities in recognition and memory as the times taken to complete the PAT and WMT were reduced compared to the mice in a comparison scopolamine-treated group. Krill oil produced an increased concentration of Ach, and this was accompanied by a decrease in AChE. As shown in a scopolamine-treated SH-SY5Y cell line, krill oil reduced the activity of AChE. Moreover, the suppression of lipid peroxidation-reflected in the finding that malondialdehyde was decreased with krill oil provision-is speculated to affect the recorded serum triglyceride and cholesterol decreases and LDL cholesterol increase. The intake of krill oil was also found to produce an improvement in brain-derived neurotrophic factor expression by stimulating the activation of cyclic AMP response element binding protein in the brain tissue. Overall, the current results imply that the provision of krill oil raises the cognition and memory by elevating neurotransmitters and by improving the serum lipid profile and nerve cell proliferation, which occur as lipid peroxidation is suppressed in the brain tissue.

CHILDHOOD TRAUMA:PSYCHIATRIC OVERVIEW (아동기 외상의 정신과적 개관)

  • Han, Sung-Hee
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.13 no.1
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    • pp.3-14
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    • 2002
  • Childhood psychic trauma appears to be a crucial factor in the development of serious disorders both in childhood and in adulthood. Traumatized children show strong tendency to revisualize or re-feel a traumatic events. Play and behavioral reenactments are frequent manifestations of both the single blow and the long-standing traumas in childhood. Those children who suffer the results of single, intense terror appear to exhibit detailed memory, retrospective reworkings and misperceptions. In long-standing or repetitive trauma, children would show psychic numbing, self-hypnosis, dissociation and rage. Child's brain is undergoing critical and sensitive periods of differentiation. During this time, developing central nervous system is exquisitely sensitive to stress. Stressor-activated neurotransmitters and hormones can play major roles in neurogenesis, migration, synaptogenesis, and neurochemical differentiation. Internal opiate system operates in some trauma and causes the victim to fail to respond, to avoid, to shut off feelings. Evidence is also accumulating in traumatology that dysfuntion of locus coeruleus and ventral tegmental neucleus system leads to catecholamine receptors hypersensitivity. This change result in hypervigilance, increased startle, affective lability, and increased autonomic nervous system hyperreactivity. Another site of action of trauma on the brain is hypothalamic-pituitary-adrenal axis. Individuals with PTSD do not have enough cortisol to halt the alarm reaction. When children are exposed to long-standing extreme events, massive attempts to protect the psyche and to preserve the self are put into gear. These developmental traumas mobilize various kinds of defense mechanisms. Massive denial, dissociation, self anesthesia, identification with aggressor and aggression turned against the self often lead to profound character changes in the youngsters.

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Effects of Acupuncture at the Sea Point on the Changes of Plasma and Tissue Levels of NO, nNOS, Norepinephrine in Rats (12경맥(經脈)의 오수혈중(五輸穴中) 합혈(合穴) 침자(鍼刺)가 백서(白鼠)의 혈위(穴位) 조직내 NO, nNOS와 조직 및 혈장 Norepinephrine의 변화에 미치는 영향(影響))

  • Kim, Young-Sun;Choi, Dong-Hee;Choi, Tae-Jin;Jang, Ho-Sun;Na, Chang-Su;Shin, Heon-Tae;Lee, Kyoung-In;Kim, Sun-Min;Pyo, Byoung-Sik;Youn, Dae-Hwan
    • Korean Journal of Acupuncture
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    • v.29 no.2
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    • pp.300-314
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    • 2012
  • Objectives : This study is to observe the changes in the expression of neurotransmitters, such as NO, nNOS, and NE, upon the needle insertion to the sea points, which is one of the five transport points. Methods : Needles were inserted into rats, on both left and right sides of all sea points, including the LU5, PC3, HT3, LI11, TE10, SI8, SP9, LR8, KI10, ST36, GB34, and BL40, which are the sea points of five transport points for 12 meridian vessels. After insertion, needles were retained for five minutes. After the retention, blood was drawn via cardiac puncture, and tissues of each point near meridian vessels were extracted to examine the changes in the expression of NO, nNOS and NE. Results : In terms of the effect in NO production, there was a significant decrease only in the LU5 point, whereas there was a significant increase in the TE10 point alone. In terms of the expression of nNOS within tissues, none of the experimental groups showed significant changes based on the results of immunohistochemistry and western blotting. Regarding the formation of norepinephrine within tissues, the HT3, SP9, and KI10 point showed a significant decrease, while the PC3 and LR8 point showed a significant increase. Production of plasma norepinephrine was significantly increased at the TE10, SP9, LR8, GB34, and BL40 point. Conclusions : The effect of needles applied at the sea points of five transport points of 12 meridian vessels on the functions of NO, nNOS, and NE could be observed, and it is considered that the effect of needle stimulation on nervous system disorders could be studied through additional researches based on this one.

Neurotransmitter and Neuroendocrine Markers as Predictors of Therapeutic Responses In Psychiatric Disorders (신경전달물질 및 신경내분비 Marker를 이용한 치료반응의 평가)

  • Han, Chang-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.2 no.1
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    • pp.3-19
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    • 1995
  • Numerous investigators have conducted extensive investigation in the search for biological markers in psychiatric illness. There are, as a test of q biological approach to the diagnosis of the psychiatric illness, tests for the neurotransmitters, their metabolites, and related enzymes, the neurotransmitter receptors, the neuroendocrine output and response, the membrane transport, peptides and eletrolytes. They are called the biological markers, and they are helpful for the diagnosis or differential diagnosis, choice of treatment or drugs, symptom improvement, predictor of recurrence and anticipation of suicidal attempt. These studies are among the main purposes that are pursued in the neuroscience and based on the potential utility of the biological markers mentioned above. Since 1970's, lots 01 biological markers' studies for the diagnosis, differential diagnosis or subtypes differentiation have been done but varieties of different opinions have been drawn since then through they could explain the charaters of main psychiatric illness(especially schizophrenia and mood disorder). But, the search for biological markers, including displines of neuroendoclinology and neurochemistry(neurotransmitter and thair metabolite), has yielded a number of putative trait merkers and state markers for psychayric illness. This paper aims to anticipate or evaluate the good response to the therapy(Therpeutic response) with lots of markers. Acoording to the diagnosis of lots of diseases or subtypes, we are going to review the papers, mainly concern with 'Is there any Marker' or 'Is any test possible to detect the improvement clinically?' 'Is it possible to predict the recurrence or good prognsis?' or 'Is it possible to select any drug or therapy to bring the good response?' The biological tests to review are mainly the metabolites of catecholamine neurotransmitter, and especially neuroendocrine test based on the knowledge that hormons of the adenohypophysis are influenced by activity of the cerebral or limbic neurons as well as the hypothalamus ones. Among them, author introduced some clinically available tests that are DST, TRH stimulation test(TRHST), GH stimulation test, and the urine MHPG test that can give us the evaluation of the treatment response, the predictor for recurrence or choice of drug that can bring a good response. So author discussed thair potential utility in clarifying, therapeutic, and prognostic issues in psychatric illness. We hope they'll be used and look forward to more active study on the different opinion.

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Effects of α1-adrenoceptor stimulation on Mg2+ release in perfused guinea pig heart (관류 기니픽 심장에서 Mg2+ 유리에 미치는 α1-adrenoceptor 자극효과)

  • Hwang, Sung-chul;Kim, Sang-jin;Kang, Hyung-sub;Lee, Seung-ok;Kang, Chang-won;Kwon, Oh-deog;Kim, Jin-sang
    • Korean Journal of Veterinary Research
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    • v.36 no.2
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    • pp.327-335
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    • 1996
  • Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

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Effect of Acupuncture(PC6) on Fos-like Immunoreactivity in the Nucleus Accumbens in Rats Sensitized to Morphine (내관(內關)부위 자침이 몰핀에 민감화된 흰쥐의 c-fos 발현에 미치는 효과)

  • Kim, Sang-Ho;Lyu, Seung-Jun;Han, Won-Ju;Kim, Mo-Kyung;Kim, Tae-Heon;Kang, Hyung-Won;Lyu, Yeoung-Su
    • Journal of Oriental Neuropsychiatry
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    • v.16 no.2
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    • pp.13-24
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    • 2005
  • Background and Objectives : Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may be linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on Fos-like immunoreactivity. Methods : Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1 min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased Fos-like immunoreactivity induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. Results and Conclusions : These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

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ATP-Sensitive $K^+$ Currents in Gastric Myocytes Isolated from Guinea-pig

  • Jun, Jae-Yeoul;Yeum, Cheol-Ho;Yun, Pyung-Jin;Park, Jong-Seong;Kim, Sung-Joon;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.85-93
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    • 1998
  • ATP-sensitive $K^+$ channels ($K_{ATP}$) were not identified in gastric smooth muscle cells. However, in tension recording of intact gastric circular muscle, lemakalim of $K_{ATP}$ channels opener in other tissues suppressed mechanical contractions and this effect was blocked by glibenclamide, a specific inhibitor of $K_{ATP}$ channels. The aims of this study were to investigate whether $K_{ATP}$ channels exist in gastric smooth muscle of guinea-pig and to know its physiological role. Whole cell $K^+$ currents activated by lemakalim were recorded from freshly isolated cells with a 0.1 mM ATP, 140 mM KCl pipette solutions. Lemakalim (10 ${\mu}M$) increased inward currents of $-224{\pm}34$ pA (n=13) at -80 mV of holding potential in bath solution contained 90 mM $K^+$. Bath-applied glibenclamide (10 ${\mu}M$) inhibited the lemakalim-activated inward currents by $91{\pm}6%$ (n=5). These lemakalim-activated inward currents were reduced by increased intracellular ATP from 0.1 to 3 mM ($-41{\pm}12$ pA) (n=5). The reversal potential of the glibenclamide- sensitive inward currents was $-5.2{\pm}2.4$ mV (n=3) in external 90 mM $K^+$ and shifted to $-14.8{\pm}3.6$ mV (n=3) in external 60 mM $K^+$, which close to equilibrium potential of $K^+$ ($E_K$). External barium and cesium inhibited the lemakalim-activated inward currents dose-dependently. The half-inhibitory dose ($IC_{50}$) of barium and cesium were 2.3 ${\mu}M$ (n=5) and 0.38 mM (n=4), respectively. 10 mM tetraethylammonium (TEA) also inhibited the lemakalim-activated inward currents by $66{\pm}15%$ (n=5). Both substance P (SP) (5 ${\mu}M$) and acetylcholine (ACh) (5 ${\mu}M$) inhibited lemakalim-activated inward currents. These results suggest that $K_{ATP}$ channels exist in the gastric smooth muscle and its modulation by neurotransmitters may play an important role in regulating gastric motility.

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In Vivo Measurement of Extracellular Monoamines and Their Metabolites in the Rat Posterior Hypothalamus Using Microdialysis Technique (미세투석법을 이용하여 흰쥐 후 사상하부에서 세포외액의 모노아민과 대사체들의 생체내 측정)

  • Sung, Ki-Wug;Kim, Seong-Yun;Cho, Young-Jin;Lee, Kweon-Haeng;Lee, Sang-Bok
    • The Korean Journal of Pharmacology
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    • v.28 no.1
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    • pp.1-9
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    • 1992
  • Catecholamines, serotonin and their metabolites were measured in the posterior hypothalamus of urethane-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) using brain microdialysis which is a recently developed experimental method to measure the release of neurotransmitters and their metabolites at the localized brain area in vivo. Microdialysis probe was implanted stereotaxically to the rat posterior hypothalamus and perfused by Ringer's solution. Monoamines and their metabolites were quantified by reverse phase high performance liquid chromatography with electrochemical detection. In vitro recovery test of microdialysis showed that there exist inverse relationship between the perfusion flow rate and the relative recovery of neurochemical compounds. The estimated extracellular concentration of dopamine was about 32 nM, of norepinephrine 50 nM, of epinephrine 50 nM, of serotonin 73 nM, of 3, 4-dihydroxyphenylacetic acid (DOPAC) 281 nM, of homovanillic acid (HVA) 181 nM, and of 5-hydroxyindoleacetic acid (5HIAA) 3767 nM in the hypothalamic perfusate of the normotensive rat. There was no difference in the basal level of monoamines between the SHR and the WKY. In contrast, the level of DOPAC, HVA and 5HIAA in SHR was higher than that in the WKY, This study demonstrated that the microdialysis technique should be an applicable tool for in vivo measurement of central neurochemical substances.

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