• The Korean Journal of Physiology
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• v.24 no.1
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• pp.51-65
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• 1990

The purpose of the present study was to examine the hemodynamic responses, especially in arterial and skin blood flows, in conjunction with the changes of plasma catecholamine levels as an indirect marker of adrenergic tone during the early stage of head-down tilt (HDT), and to evaluate the early physiological regulatory mechanism in simulated weightlessness. Ten mongrel dogs, weighing8\;{\sim}\;14\;kg, were intravenously anesthetized with nembutal, and postural changes were performed by using the tilting table. The postural changes were performed in the following order: supine, prone, HDT $(-6^{\circ}C)$ and lastly recovery prone position. The duration of each position was 30 minutes. The measurements were made before, during and after each postural change. The arterial blood flow $({\.{Q}})$ at the left common carotid and right brachial arteries was measured by the electromagnetic flowmeter. Blood pressure (BP) was directly measured by pressure transducer in the left brachial artery. To evaluate the peripheral blood flow, skin blood flow $({\.{Q}})$ was calculated by the percent changes of photoelectric pulse amplitude on the forepaw, and skin temperature was recorded. The peripheral vascular resistance (PR) was calculated by dividing respective mean BP values by ${\.{Q}}$ of both sides of common carotid and brachial arteries. Heart rate (HR), respiratory rate (f) and PH, $Po_{2},\;Pco_{2}$ and hematocrit of arterial and venous blood were also measured. The concentration of plasma epinephrine and norepinephrine was measured by radioenzymatic method. The results are summarized as follows: Tilting to head-down position from prone position, HR was initially increased (p<0.05) and BP was not significantly changed. While ${\.{Q}}$ of the common carotid artery was decreased (p<0.05) and PR through the head was increased, ${\.{Q}}$ of the brachial artery was increased (p<0.05) and PR through forelimbs was decreased. ${\.{Q}}$ of the forepaw was initially increased (p<0.05) and then slightly decreased, on the whole revealing an increasing trend. Plasma norepinephrine was slightly decreased and the epinephrine was slightly increased. f was increased and arterial pH was increased (p<0.05). In conclusion, the central blood pooling during HDT shows an increased HR via Bainbridge reflex and an increased ${\.{Q}}$ of the forepaw and brachial ${\.{Q}}$, due to decreased PR which may be originated from the depressor reflex of cardiopulmonary baroreceptors. It is suggested that the blood flow to the brain was adequately regulated throughout HDT $(-6^{\circ}C)$ in spite of central blood pooling. And it is apparent that the changes of plasma norepinephrine level are inversely proportional to those of ${\.{Q}}$ of the forepaw, and the changes of epinephrine level are paralleled with those of the brachial ${\.{Q}}$.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• Sleep Medicine and Psychophysiology
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• v.3 no.1
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• pp.15-24
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• 1996

After rapid eye movement(REM) sleep was idenified in 1953, a lively interest developed concerning a possible role of this kind of sleep in memory processes. The author reviewed studies relating REM to memory/learning. Many studies in animals and humans gave substantial evidence for relating REM sleep to memory function. The evidence supporting the position taken in this paper comes from experiments showing that : (1) learning session is followed by the significant augmentation of REM sleep : (2) REM sleep deprivation, prior to learning or immediately thereafter, impairs the formation of a permanent memory/learning : (3) there is a vulnerable period of time(eg, REM sleep "window") following succussful learning, during which REM sleep deprivation results in memory impairment : (4) theta rhythm which develops during REM sleep induces long-term potentiation in hippocampus : (5) there are some evidences providing the relationship of neurotransmitter systems to the maintenance of REM sleep and memory storage processes.

• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.197-211
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• 2000

The pineal body have been known to be affected by superior cervical ganglia, and most of its nerve fibers containing peptidergic neurotransmitters have been considered to be originated from this ganglia. To confirm this relationships, some peptidergic neurotransmitters were identified in both of pineal body and superior cervical ganglia of the Korean native goat, which were divided into two group; breeding season and non-breeding season. The localizations of two catecholamine-synthesizing enzymes; tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), were investigated by immunohistochemistry in the superior cervical ganglia and the pineal body of adult Korean native goats. Substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and galanin (GAL) were also identified in these organs by immunohistochemical and double immunofluorescent methods. In superior cervical ganglia, immunoreactivities for TH and DBH were confirmed in the same ganglion cells. The immunoreactivites for SP, VIP(only in male), NPY and GAL were identified in both of ganglion cell bodies and nerve fibers in the ganglia. CGRP immunoreactivity, however, was observed only in nerve fibers. Most NPY- and VIP-immunoreactive(IR) ganglion cells also contained TH. SP and TH were colocalized in the cell bodies, but not in the nerve fibers. TH immunoreactivity was shown in almost all of ganglion cells in the superior cervical ganglia. The immunoreactivity for NPY had some seasonal variation and was stronger in breeding season than in non-breeding season. In pineal body, lots of TH-IR fibers were observed throughout the parenchyma including the pineal stalk and most of them also contained DBH. SP- and NPY-IR fibers were also immunostained with TH or DBH. But a few SP- and NPY-IR fibers were not colocalized with TH or DBH. Exceptionally, a bipolar neuron-like cell was observed to be immunostained with NPY in the pineal body. A few CGRP and GAL-IR fibers were observed, while VIP-IR fibers were not present. It is concluded that most TH- and DBH-IR fibers as well as the peptidergic immunoreactive fibers of the pineal body might be originated from the superior cervical ganglia. Some peptidergic immunoreactive fibers, however, might be come from other regions of brain. We also suggest that NPY in pineal body plays a important role for pineal function. The seasonal variation of NPY immunoreactivity indicates that the synthesis and use of NPY may be different between in breeding and non-breeding seasons.

• Development and Reproduction
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• v.13 no.4
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• pp.257-264
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• 2009

A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA ($200{\mu}g$ in $10{\mu}\ell$ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72${\pm}$0.02AU, p<0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39${\pm}$0.03AU, p<0.001; CRH, control:6-OHDA=1:0.76${\pm}$0.07AU, p<0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cg$\alpha$), LH beta subunit (LH-$\beta$), and FSH beta subunit (FSH-$\beta$) in pituitaries from 6-OHDA group compared to control values (Cg$\alpha$, control:6-OHDA=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, control:6-OHDA=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, control:6-OHDA=1:0.84${\pm}$0.05AU, p<0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86${\pm}$0.04AU, p<0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.47-62
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• 1981

d-amphetamine이 사람에서 paranoid schizophrenia와 아주 유사한 model psychosis를 일으키며 또한 사람과 실험동물에서 실제 정신분열증에서 뚜렷이 관찰되는 behavioral perservation을 일으킬 수 있음이 관찰되었다. 이에 많은 학자들은 이러한 양상의 행동변화가 정신분열증의 원인 추구에 중요한 의미를 주는 뇌변화를 반영할지도 모른다는 생각에 많은 연구를 거듭하여 왔다. 지금까지는 주로 catecholamine기전에 대하여 집중적 연구가 수행되어져 왔으나 최근에는 d-amphetamine의 약리기전의 일부는 5-HT기전이 차지하고 있으며, 여러 행동변화에는 catecholaimin 보다 5-HT 가 더 중요하게 관계하고 있다는 주장이 나오고 있다. 또한 d-amphetamine은 시험관내에서 MAO 특히 신경전달물질 분해요소인 A type를 가역적으로 억제할 수 있음이 보고되어 많은 흥미를 끌어왔으나 생체내에서의 억제여부는 직접적으로 확인이 되고 있지 않다. 그러나 최근에 Braestrup(1977)과 El Hait(1978)등은 간접적인 방법으로 생체내에서도 억제시킬 수 있음을 보고하고 있다. 이에 저자는 d-amphetamine에 의해 야기되는 행동변화와 그 밑바탕을 이루는 생화학적 기전에 5-HT가 차지하는 역할을 알아보기 위해서 다음의 실험을 시행하였다. 첫째, d-amphetamine의 급성, 만성 투여가 5-HT의 5-HIAA 로의 turnover와 MAO활성도에 어떤 영향을 미치며, 더 나아가서 이 양자사이에 어느 정도 상관관계가 있는지를 알아보기 위해서 d-amphetamine을 투여한 후 시간 경과에 따라서 뇌내 5-HT, 5-HIAA, 5-HT turnover rate와 MAO 활성도를 측정하였다. 둘째, d-amphetamine, 5-HT 합성을 증가시키는 약물과 합성을 억제시키는 약물을 투여하고, 위의 생화학적 실험과 행동관찰을 병합 실시하여 비교분석하였다. 그 결과는 다음과 같다. 1) d-amphetamine (6 mg/kg)을 급성투여시, 뇌내 5-HT함량이 투여 1시간 후에 최고로(대조치의 123%, p<0.001) 증가되다가 이후 감소하며, 5-HIAA 함량은 처음 15분부터 감소하기 시작하다가 30분에 최저로 떨어지며(대조치의 78%, p<0.005) 이후 증가하여 24시간째는 약간 대조치 이상으로 회복되었다. 미토콘드리아 MAO활성도는 1시간째에 최저로 떨어지다가(대조치의 89%, p<0.05)이후 회복하기 시작하여 24시간째에 약간 대조치 이상으로 회복되었다. 5-HT의 turnover rate는 MAO활성도 변화와 거의 같은 변화를 보였다. 2) 만성투여시 (하루 2번, 14일간 투여)는 5-HT 함량, 5-HIAA 함량, MAO 활성도 및 5-HT turnover rate 모두가 중등도로 감소되었다. (각각 대조치의 87%, 69%, 80%, 79%). 3) MAO 활성도와 5-HT turnover rate 사이에는 높은 상관관계가 있었다. (r=0.866, p<0.001, N=94). 4) MAO 활성도의 역동학 실험에서는 대조치에 비해 투여군에서 Km 값은 의미가 있는 증가가 있었으나 $V_{max}$값은 큰 변동이 없었다. 5) d-amphetamine을 급성 투여할때는 sleeping과 lying components는 상당한 감소를 보인 반면, locomotor activity 는 1시간까지는 상당한 증가를 보였으며 용량이 적을수록 더 큰 증가가 있었다. 반면 stereotypy는 1시간까지 용량이 증가할수록 더 큰 증가가 나타나서 locomotor activity에서 stereotypy 의 증가로 이행을 나타내었다. 만성 투여시는 locomotor activity는 점차적인 감소를 보였으나 stereotypy는 점차적인 증가가 나타나서 14일쯤에는 평형에 도달하였다. 6) PCPA 단독 투여군(400 mg/kg, 3번)에 있어서는 5-HT와 5-HIAA 함량의 상당한 감소가 나타났으나 MAO 활성도와 행동에는 큰 변화를 나타내지 않았다. PCPA전 처치군에 있어서도 5-HT와 5-HIAA 함량은 마찬가지로 상당한 감소를 나타내었으나 gnawing, sniffing과 locomotor activity는 더 증가를, stereotyped head weaving, forepaw treading과 hindlimb abduction은 상당한 감소를 나타내었다. 7) L-tryptophan(100 mg/kg)단독 투여시는 5-HT 함량은 약간 증가를 나타내었으나 5-HIAA 함량은 상당한 증가를 보였다. MAO활성도나 행동은 큰 변화없었다. L-tryptophan 전처치군에 있어서는 5-HT 함량은 더 큰 증가를 보였으나, 5-HIaa 함량은 MAO 활성도는 별 변화없었으며 stereotypedlateral head waving, forepaw treading 과 hindlimb abduction은 증가를, locomotor activity, gnawing과 sniffing components는 감소를 나타내었다. 8) d-amphetamine 단독투여, 혹은 L-tryptophan 전처치, PCPA 전처치후 측정한 5-HT 함량과 stereotyped head weaving, forepaw treading, hinilimb abduction components 사이에는 높은 상관관계가 있었다(r=0.789, p<0.001). 반면 5-HT 함량과 locomotor activity, stereotyped gnawing과 sniffing components 사이에는 약한 음성의 상관관계가 있었다. (r=0.554, p <0.005). 이상의 결과로 미루어 볼때 5-HT의 5-HIAA 로의 turnover rate 는 주로 MAO 활성도에 의해서 조절되며 5-HT 기전이 d-amphetamine에 의해서 야기된 여러 행동변화 중 상당한 부분에서 중요한 역할을 하리라고 생각된다.