Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K⁺ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

Comparison of Fornix and Stria Terminalis Connectivity among First-Episode Schizophrenia, Chronic Schizophrenia and Healthy Controls

OBJECTIVES: Disrupted integrities of the fornix and stria terminalis have been suggested in schizophrenia. However, very few studies have focused on the fornix and stria terminalis comparing first-episode schizophrenia (FESZ), chronic schizophrenia (CS), and healthy controls (HCs) with the application of diffusion-tensor imaging (DTI) technique. The objective of this study is to compare the connectivity of the fornix and stria terminalis among FESZ, CS, and HCs. METHODS: We included the 44 FESZ patients, 39 CS patients and 20 HCs in this study. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics to analyze the connectivity of fornix and stria terminalis. In addition, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate clinical symptom severities. RESULTS: There were no significant differences between the FESZ, CS, and HCs in age, sex, education years. The SAPS and SANS scores of the schizophrenia groups showed no significant differences. FA values of the right fornix cres/stria terminalis in the CS group were significantly lower than those in FESZ and HCs. There were no significant differences of FA values of the right fornix cres/stria terminalis between the FESZ and the HCs. Pearson correlation analyses revealed that significant correlation between FA values of the right fornix cres/stria terminalies of the the FESZ group and positive, negative symptom scales, and FA values of the right fornix cres/stria terminalis of the CS group and negative symptom scales. CONCLUSIONS: This study shows that FA values of the fornix and stria terminalis in the CS were lower than in the FESZ and the HCs. These results suggest that the fornix and stria terminalis can play a role in pathophysiology of schizophrenia. Thus current study can broaden our understanding of the pathophysiology of schizophrenia.

Differential Histone Acetylation in Sub-Regions of Bed Nucleus of the Stria Terminalis Underlies Fear Consolidation and Extinction

OBJECTIVE: The hallmark of anxiety disorders is excessive fear. Previous studies have suggested that selective neural projections from Basal nucleus of stria terminalis (BNST) to amygdala and vice-versa precisely control the fear learning process. However the exact mechanism how the BNST controls fear consolidation and its extinction is largely unknown. In the present study we observed the changes in the BNST sub-regions following fear conditioning and its extinction. METHODS: The change in the number of positive neurons was determined by immunohistochemistry for Acetyl H3 (Histone 3), Acetyl H4 (Histone 4), cAMP response element binding Protein (CBP) and c-fos in three sub-regions of the BNST namely the anterio-lateral BNST (STLP) and anterio-medial BNST (STMA), and lateral-ventral BNST (STLV) of rats subjected to auditory fear conditioning and extinction. RESULTS: We found significant increase in the number of CBP, acetyl H3 and acetyl H4 positive neurons in the STMA and STLV but not in the STLP after fear conditioning. However, following fear extinction the number of CBP, acetyl H3 and acetyl H4 positive neurons increased significantly in the STLP but not in the STMA and STLV. Similar changes were observed in the number of c-fos positive neurons after fear consolidation and extinction. CONCLUSION: The results from this study suggest that the differential histone acetylation in the different sub-regions of the BNST following fear learning and its extinction may be responsible for changes in the neuronal activation patterns resulting in either fear or less fear.

Time course effects of lithium administration on spatial memory acquisition and cholinergic marker expression in rats

The effects of chronic lithium exposure on spatial memory in rats remain controversial. In this study a time course of the effects of lithium, administered systemically, on spatial memory acquisition in Morris water maze was investigated. Lithium [600 mg/L] was administered to four groups of rats in their drinking water; the first group of animals received lithium for one week, the second group for two weeks, the third group for three weeks, and the fourth group for four weeks. As controls, four groups of animals received only normal drinking water for the same period of time. Toward the end of their lithium or water treatment, all animals were trained for four days; each day included one block and each block contained four trials. Test trials were conducted 48 hrs after completion of the lithium treatment. Escape latency, traveled distance and swimming speed were evaluated during testing trials. Brain tissues from animals were processed according to the standard protocols for immunohistochemical analysis. Lithium treatment decreased escape latency and traveled distance, but not swimming speed, compared with controls, suggesting significant spatial memory acquisition enhancement by lithium. Quantitative analysis showed that lithium, particularly after four weeks of exposure, significantly increased the number and density of immunostained ChAT-containing [choline acetyltransferase] neurons in the medial septal area in comparison with control groups. There was also a significant correlation between the number of immunostained ChAT neurons and behavioral measures. These results suggest that chronic oral administration of lithium causes spatial memory acquisition improvement in rats and an increase in ChAT immunostaining levels in medial septal nuclei

Vasopressin mediates the cardiovascular effects of GABAergic system in the bed nucleus of the stria terminalis

The nucleus bed of the stria terminalis [BST] is a part of the limbic system. Previous studies have shown that inhibition of GABA A receptor increases blood pressure and heart rate. This study was performed to find the possible mechanisms and circuits that mediate these responses. In 39 urethane-anesthetized male rats the femoral artery and vein were cannulated for recording the blood pressure and heart rate and drug injection respectively. Trachea was cannulated to ease ventilation, and bicuculline was unilaterally microinjected into the BST using micropipette. The maximum changes of mean arterial pressure [MAP] heart rate [HR] were compared with the preinjection values using the paired t-test. Injection of bicuculline methiodide [BMI, 100 pmol/100 nl], a GABAA antagonist, caused a significant increase in the MAP [41.3 +/- 5.1 mmHg] as well as in the HR [33.2 +/- 5.6 beats/min]. Administration [i.v.] of the muscarinic receptor blocker, homatropine methyl bromide had no effect on the magnitude of mean arterial pressure or heart rate responses to BMI, suggesting that the parasympathetic system is not involved in these responses. However administration [i.v.] of the nicotinic receptor blocker, hexamethonium bromide, althought it had no effect on the magnitude of mean arterial pressure response, did abolish heart rate response to BMI, indicating that the sympathetic system is involved in the bradycardic effect of GABA. On the other hand, administration [i.v.] of a selective vasopressin V1 receptor antagonist abolished the pressor effect of BMI, which suggests that the GABAergic system of the BST decreases the arterial pressure via tonic inhibition of vasopressin release. We demonstrated, for the first time, that inhibition of GABAA, receptors increase blood pressure and heart rate via tonically inhibiting vasopressin release and sympathetic outflow to the heart

Participação dos receptores serotoninérgicos do subtipo 5-HT³ localizados na área septal medial sobre o controle da ingestão de água e sal em ratos sódio-depletados / Participation of serotonin receptor subtype 5-HT ³ located in the medial septal area on the control of water intake and salt in sodium-depleted rats

A regulação do equilíbrio hidroelétrico é desempenhada por um conjunto de mecanismos viscerais e comportamentais, nos quais se incluem a ingestão de água e sal controlados por diversos neurotransmissores e áreas cerebrais. Estudos sugerem a participação de mecanismos Serotoninérgicos na indução das respostas fisiológicas relacionadas com a regulação da ingestão de água e sal. No presente estudo analisamos o envolvimento dos receptores 5-HT³ Serotoninérgicos localizados na ASM sobre a ingestão de água e sal em ratos sódio-depletados. Verificamos que a estimulação farmacológica específica dos receptores Serotoninérgicos 5-HT³ localizados na ASM, pelo agonista 5-HT³ seletivo m-CPBG, aumenta a ingestão de sal em ratos sódio-depletados. A especificidade deste efeito parece assegurada pelo fato de que o pré-tratamento com Ondansetrona, antagonista dos receptores Serotoninérgicos 5-HT³, aboliu completamente a elevação na ingestão de sal produzida pela administração do m-CPBG na ASM. Esse efeito Natriorexigênio parece não ser dependente de alterações na pressão arterial, visto que a micro-injeção na ASM do m-CPBG não foi capaz de modificar este parâmetro. Além disso, constatamos que a administração isolada do antagonista Ondasterona é incapaz de produzir efeito significativo sobre a ingestão de água e sal em ratos sódio-depletados. Tomando em conjunto os achados acima mencionados sugere-se que os receptores Serotoninérgicos do subtipo 5-HT³ localizados na ASM quando ativados farmacologicamente são capazes de ativar mecanismos centrais envolvidos com a procura e a ingestão de sódio.

The medial septum acts through the medial preoptic area for thermoregulation and works with it for sleep regulation.

The chronic changes in sleep-wakefulness (S-W), body temperature (Tb), locomotor activity (LMA) and thermal preference were studied in male Wistar rats after the destruction of neurons in both the medial preoptic area (mPOA) and the medial septum (MS) by intracerebral injection of N-methyl-D-aspartic acid. An increase in the Tb, and a preference for higher ambient temperature (Tamb) of 30 degrees C were observed after the combined lesion of the mPOA and the MS. Similar changes were reported to occur after the lesion that was restricted to the mPOA. But these alterations were in contrast to the decrease in Tb and preference for lower Tamb, observed after the MS lesion. The thermostat of the brain would have been reset at a higher level after the combined lesion, as there was an increase in Tb, along with a preference for a higher Tamb, and an increase in LMA. There was a reduction in the frequency and the duration of the slow wave sleep (SWS) episodes, and a reduction in the frequency of the paradoxical sleep (PS) episodes after the combined lesion. The destruction of the MS neurons was probably responsible for the reduction in the frequency of SWS, whereas the loss of mPOA neurons was responsible for the decrease in the duration of SWS and frequency of PS. It can be suggested that the MS exerts its influence on thermoregulation through the mPOA. However, the MS and the mPOA seem to play independent, but complementary roles in sleep promotion.

Hipertrofia septal asimétrica y anestesia para cirugía laparoscópica / Hypertrophies septal asymmetric and anesthesia for laparoscopic surgery

Se trata de una paciente de 78 años de edad quien venía siendo estudiada por el servicio de ginecología y cirugía de colon y recto de la FSFB, por un cuadro de 10 meses de evolución consistente en dolor abdominal de características viscerales asociado con pérdida de peso de 10 kg. Para continuar el estudio de la posible etiología de sus síntomas, se hace necesaria la realización de una laparoscopia con fines diagnósticos para descartar una patología neoplásica . Como antecedentes importantes la paciente tiene diagnóstico de enfermedad diverticular de colon izquierdo, nódulos pulmonares en seguimiento los cuales no habían tenido cambios en los controles radiológicos, e Hipertrofia Septal Asimétrica diagnosticada hace 18 años, cuyo último control ecocardiográfico reporta gradiente de 126 mmHg a traves del tracto de salida del ventrículo izquierdo. Debe anotarse que durante la realización del ecocardigrama la paciente se encontraba con frecuencias cardíacas elevadas. La paciente venía en tratamiento con metoprolol 100 mg cada 12 horas y diltiazem...

Atenolol or butoxamine injection at the lateral septum doesn't inhibit male sexual behavior in rats.

To investigate the role of specific adrenoreceptors subtypes on sexual behavior, atenolol, butoxamine, a mixture of atenolol and butoxamine, and saline (vehicle) were injected into the lateral septum in four different groups of sexually active male rats. Application of a mixture of atenolol and butoxamine produced inhibition of copulatory activity. On the other hand, application of either atenolol or butoxamine alone did not inhibit copulatory activity. But it produced stimulation of some of the components of male sexual behavior. Inability of either atenolol or butoxamine to inhibit the male sexual behavior, and inhibition of the same by the mixture of atenolol and butoxamine, indicate that both beta-adrenoreceptors at the lateral septum are involved in the elaboration of male sexual behavior. Stimulation of some components of sexual behavior on application of atenolol or butoxamine could be attributed to an unbalanced activity of beta-adrenoreceptors.

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field

The medial septum participates in the modulation of exploratory behavior triggered by novelty. Also, selective lesions of the cholinergic component of the septohippocampal system alter the habituation of rats to an elevated plus-maze without modifying anxiety indices. We investigated the effects of the intraseptal injection of the cholinergic immunotoxin 192 IgG-saporin (SAP) on the behavior of rats in an open-field. Thirty-nine male Wistar rats (weight: 194-230 g) were divided into three groups, non-injected controls and rats injected with either saline (0.5 æl) or SAP (237.5 ng/0.5 æl). Twelve days after surgery, the animals were placed in a square open-field (120 cm) and allowed to freely explore for 5 min. After the test, the rats were killed by decapitation and the septum, hippocampus and frontal cortex were removed and assayed for acetylcholinesterase activity. SAP increased acetylcholinesterase activity in the septum, hippocampus and frontal cortex and decreased the total distance run (9.15 ± 1.51 m) in comparison to controls (13.49 ± 0.91 m). The time spent in the center and at the periphery was not altered by SAP but the distance run was reduced during the first and second minutes (2.43 ± 0.36 and 1.75 ± 0.34 m) compared to controls (4.18 ± 0.26 and 3.14 ± 0.25 m). SAP-treated rats showed decreased but persistent exploration throughout the session. These results suggest that septohippocampal cholinergic mechanisms contribute to at least two critical processes, one related to the motivation to explore new environments and the other to the acquisition and storage of spatial information (i.e., spatial memory)

Changes of the Cholinergic Innervation to the Hippocampus after Entorhinal Cortex Lesion in Rat / 대한해부학회지

The hippocampus is known as involved in learning and memory functions and the entorhinal cortex plays a crucial role as a gateway connecting the several areas and hippocampal formation. Entorhinal cortex lesions have been employed in numerous studies as the Alzheimer's disease model. The purpose of this study were to identify the CNS hip-pocampal and cholinergic pathway and to investigate the morphological changes of the hippocampal cholinergic inner-vations by using the Pseudorabies virus injection into the hippocampus after entorhinal cortex lesions. The pseudorabies virus and double labelled neurons (ChAT and PRV) were distributed at several different nuclei including agranular insular cortex, bed nucleus of stria terminalis, central amygdala, globus pallidus, lateral segment, lateral hypothalamic area, laterodorsal tegmental nucleus, medial septal nucleus, mesencephalic reticular nucleus, periaqueductal gray matter and substantia innominata The morphological changes were observed in the hippocampal cholinergic innervation after entorhinal cortex lesions. These data suggested that the hippocampal cholinergic innervation showed morphological changes throughout the whole brain areas after entorhinal cortex lesion.

Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II

We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non-peptides and selective antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] angiotensin II (ANG II) (40 nmol) (a non-selective peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on the water and salt appetite, diuresis and natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250-300 g. The volume of drug solution injected was 0.5 æl over a period of 10-15 s. The responses were measured over a period of 120 min. ANG II alone injected into the MSA induced an increase in all the above parameters (8.1 ± 1.2, 1.8 ± 0.3, and 17.1 ± 1.0 ml, 217 ± 25 æEq/120 min, and 24 ± 4 mmHg, respectively, N = 10-12) compared with vehicle-treated rats (1.4 ± 0.2, 0.6 ± 0.1, and 9.3 ± 0.5 ml, 47 ± 5 æEq/120 min, and 4.1 ± 0.8 mmHg, respectively, N = 10-14). Pretreatment with losartan and [Sar¹, Ala8] ANG II completely abolished the water and sodium intake, and the pressor increase (0.5 ± 0.2, 1.1 ± 0.2, 0.5 ± 0.2, and 0.8 ± 0.2 ml, and 1.2 ± 3.9, 31 ± 4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and sodium excretion induced by ANG II (13.9 ± 1.0 ml and 187 ± 10 æEq/120 min, respectively, N = 9). Pretreatment with PD 123319 and [Sar¹, Ala8] ANG II blocked the urinary and sodium excretion (10.7 ± 0.8, 9.8 ± 0.7 ml, and 67 ± 13 and 57 ± 17 æEq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 ± 0.3, 1.1 ± 0.1 ml, and 12 ± 3 mmHg, respectively, N = 9-10). These results suggest the angiotensinergic effect of the MSA on the AT1 and AT2 receptors of the PVN in terms of water and sodium homeostasis and MAP modulation

Accumulation of Peroxidase-Positive Granules with Ageing in SAMP10 and SAMR1 Mouse Brains / 대한해부학회지

The microscopic and quantitative study reported here examined peroxidase-positive granules in the senescenceacceleration prone mouse (SAMP10) brain and the senescence-resistant mouse (SAMR1) brain. Three-month-old and 14-month-old SAMP10 and SAMR1 mice were used in this stusy. Coronal brain sections were made, and then incubated with medium containing 0.05% 3, 3'-diaminobenzidine and 0.003% H2O2 in 0.1 M PB to visualize endogenous peroxidase activity. Peroxidase-positive granules were rarely found in the three-month-old SAMR1, whereas a few positive granules were observed in the young SAMP10 brains. Forteen-month-old animals showed frequent labelling for endogenous peroxidase. This labelling was distributed exclusively in periventricular regions such as the periventricular and arcuate hypothalamic nuclei surrounding the third ventricle, and the periventricular portion of the caudate-putamen and lateral septal nuclei surrounding the lateral ventricle. Double labelling with GFAP antiserum indicated that most DAB-positive granules in these regions were located within astrocytes. Image analysis showed that significantly more peroxidase-positive granules occurred with advancing age in both the SAMP10 and SAMR1 brains. However, the amount of these inclusions was significantly greater in the young as well as the aged SAMP10 brain than in the age-matched SAMR1 controls. Electron microscopic examination of the aged SAMP10 brain showed localization of endogenous peroxidase in astrocytes. They appeared as accumulated granules or inclusion bodies with homogeneously high electron density, rather than as diffusely scattered small particles. In summary, DAB-stained granules indicating the presence of peroxidase activity accumulated with ageing in both SAMP10 and SAMR1 brains, mainly in astrocytes of the periventricular brain regions. Further, the accumulation was more accelerated from younger ages and more extensively in the SAMP10 brain. These results suggest that astroglial changes might occur from young period in the periventricular region of the SAMP10, which might be associated with the neurological senescence in the SAMP10.

Increase of peroxynitrite production in the rat brain following transient forebrain ischemia

It has been proposed that nitric oxide is involved in the pathogenesis of cerebral ischemia-reperfusion. Because superoxide production is also enhanced during reperfusion, the cytotoxic oxidant peroxynitrite could be formed, but it is not known if this occurs following global forebrain ischemia-reperfusion. We examined whether peroxynitrite generation is increased in the vulnerable regions after forebrain ischemia-reperfusion. Transient forebrain ischemia was produced in the conscious rat by four-vessel occlusion. Rats were subjected to 10 or 15 min of forebrain ischemia. Immunohistochemical method was used to detect 3-nitrotyrosine, a marker of peroxynitrite production. 3-Nitrotyrosine immunoreactivity was enhanced in the hippocampal CA1 area 3 days after reperfusion. Furthermore, in rats subjected to ischemia for 15 min, this change was also observed in the lateral striatal region and the lateral septal nucleus 2apprx3 days after reperfusion. The cresyl violet staining of adjacent sections showed that neuronal cell death was induced in parallel with the nitrotyrosine immunoreactivity in the hippocampal CA1 area and the lateral striatal region. Our findings suggest that oxygen free radical accumulation and consequent peroxynitrite production play a role in neuronal death caused by cerebral ischemia-reperfusion.

The expression of Protein Kinase C Isozymes in the Rat Brain / 대한해부학회지

The mRNA expression of protein kinase C (PKC) isozymes (alpha, beta, gamma, delta, epsilon and zeta) in the rat nervous system was investigated with in situ hybridization histochemistry. In the central nervous system of rat, each PKC isozyme mRNAs was expressed in isozyme-specific pattern. PKC alpha mRNA was highly expressed in the olfactory bulb, piriform cortex, hippocampus, substantia nigra compacta, and inferior olive. The expression of PKC beta was highest in the olfactory tubercle, piriform cortex, caudate putamen, accumbens nucleus, neocortex, hippocampus, basolateral amygdaloid nucleus, pontine nucleus, and cerebellum. PKC gamma mRNA was distributed in the caudate putamen, hippocampus and cerebellum and PKC delta was expressed in the thalamus. PKC epsilon had widespread distribution, with relatively high levels in the anterior olfactory nucleus, olfactory tubercle, tinea tecta, piriform cortex, dorsal lateral septal nucleus, neocortex, hippocampus and cerebellum. PKC zeta had widespread and low expression. The spacially differential expression of PKC isozymes (alpha, beta, gamma, delta, epsilon and zeta) suggests that each PKC isozyme may be related with specific cellular function in the nervous system.

Immunohistochemical Study on the Nitric Oxide Synthase in the Developing Rat Brain / 대한해부학회지

Nitric oxide(NO) is thought to play an important role in development and plasticity of brain. In this study, we aimed to examine the expression of neuronal NOS and NADPH-diaphorase (NADPH-d) activity in the developing rat brain. The results show that there is a great variation in the time of appearance of the earliest NOS containing cells depending on their location: At the 15th embryonic day weakly stained cells were present in caudate-putamen, and neurons in the sensory trigeminal nucleus and the solitary nucleus displayed an intense staining. The NOS neurons in orbital neocortex, bed nucleus of stria terminalis, paraventricular hypothalamic nucleus, lateral hypothalamic area and mammillary body appeared first at the 18th embryonic day. The supraoptic nucleus and superior and inferior colliculi also weakly labeled at the 18th embryonic day, At the loth embryonic day, positive cells appeared in horizontal limb of diagonal band, anterior olfactory nucleus and parafascicular thalamic nucleus. In the cerebellum, weak NOS staining was present in fibers and cells situated below Purkinje cert layer. The Purkinje cell layer displayed a weak, rather diffuse activity throughout the cerebellum at postnatal day 0. At the 4th postnatal day. the reaction product in the Purkinje cell layer became more distinct. At the 10th postnatal day, the inner part of molecular layer became populated by NOS positive basket cells, and the reaction products on the Purkinje cells began to disappear. The present results showed that NOS in the rat brain is expressed in different populations of neurons at different stages of development. This expression pattern of NOS suggests that NO may play a role in the developmental remodelling of the mammalian brain.

The Changes of c-fos and c-jun after Capsaicine Treatment in the Rat Brain / 대한해부학회지

The expression of c-fos and c-jun in the brain of the rat after capsaicin treatment was investigated by in situ hybridization, dot blot hybridization and immunocytochemical methods. Adult male Sprague-Dawley rats[200g] were used for this study. The first set of rats received a single subcutaneous injection of capsaicin[50mg/Kg] dissolved in 10% Tween-80 and 10% ethanol in saline. The rats were decapitated 1, 3, 5, 10, 24, 72 hours and 1 week after capsaicin treatment. The control set of rats were treated with saline instead of capsaicin. In situ hybridization and dot blot hybridization were carried out. O1igonucleotide probe complimentary to c-fos mRNA sequences were used for this study and labeling of oligonucleotides was accomplished using the DNA tailing kit. The expression of c-fos mRNA on the nucleus of neurons in in situ hybridization was observed throughout the brain, and was especially abundant in the olfactory cortex, nucleus of diagonal band of Broca, habenular nuclei, periaqueductal gray, parabrachial nucleus, entopeduncular nucleus, ventral posterolateral nucleus of the thalamus and cerebellum. Compared to the control rats, c-fos mRNA were increased 24 hours after capsaicin injection and gradually decreased after 72 hours, returning to the normal control level 1 week after capsaicin injection. c-fos mRNA was detected only 1 week after capsaicin injection in the various areas of the brain. The fos protein-like immunoreactivity was initially somewhat decreased at 24 hours, but increased at 72 hours and reactions was maximally observed at 1 week after capsaicin treatment. But Jun protein immunoreactivity was not increased, on the contrary, it was even decreased both in numbers of reactive cells and immunoreactivity 1 week after capsaicin injection. From the above results, c-fos gene expression was pronounced in the nucleus concerned with pain, olfaction and taste such as VPL nucleus of the thalamus, olfactory cortex and parabrachial nucleus, in the limbic system concerned with stress and emotion such as nucleus of diagonal band of Broca, periaqueductal gray and habenular nucleus, in the structure concerned with somatic motor function such as entopeduncular nucleus and cerebellum. Also, the c-fos gene was activated by the capsaicin early in the course of effects, then the fos protein increased as a results of c-fos activation. On the other hand, c-jun did not respond to capsaicin treatment early in the course, but Jun protein decreased late in the course of capsaicin effects.

Immunohistochemical Studies on Calcitonin Gene-related Peptide Cell in Rat Brain / 대한해부학회지

These studies were performed to identify the localization, and neuronal function of calcitonin gene-related peptide[CGRP] in the neural axis of rat stomach by retrograde tracing and immunohistochemical techniques. After injection of pseudorabies virus Bartha strain[PRV] as tracer between serosa and muscle layer of stomach, the rats were perfused and the brains were removed. PRV-immunoreactive cells were observed in central nucleus of amygdaloid, insular cortex, subfornical organ, bed nucleus of stria terminalis, paraventricular nucleus, organum vasculosum of terminalis, suprachiasmatic nucleus, lateral hypothalamic area, K lliker-Fuse nucleus, parabrachial nucleus, locus ceruleus, A1 noradrenaline area, A5 noradrenaline area, area postrema, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius and raphe nuclei. CGRP-immunoreactive cells are observed in insular cortex, bed nucleus of stria terminalis, paraventricular nucleus, lateral hypothalamic area, parabrachial nucleus, area postrema, nucleus tractus solitarisu, neucleus ambiguus, facial nucleus, hypoglossal nucleus and raphe nuclei. The dobule immunofluorescent study was carried out to examine the coexistence of CGRP and PRV in several nuclei : insular cortex, bed nucleus of stria terminalis, paraventricular nucleus, later hypithalamic area, parabrachial nucleus, area postrema, nucleus tractus solitarius and raphe nuclei. At the results of double immunofluorescent study, we could not observe the double immunoreactive neurons CGRP and PRV in those nuclei but raphe nuclei. These results suggest that CGRP should not have a neural functions in the neurons in nuclei projecting to rat stomach except raphe nuclei.

The Studies on Central Neural Axis to Innervate Rat Digastric Muscle / 대한해부학회지

The present study has been performed to investigate the neural axis of rat digastric muscle using viral tracer, pseudorabies virus. The upper nuclei to innervate digastric muscle were in accumbens nucleus, agran-ular insular cortex, central nucleus of amygaloid, lateral septal nucleus, frontal cortex, and subfornical organ etc, in telencephalon ; arcuate hypothalamic nucleus, lateral hypot-halamic area, medial preoptic nucleus, bed nucleus of stria terminalis, dorsomedial hypot-halamic nucleus, suprachiasmatic nucleus, paraventricular nucleus, and retrochiasmatic area etc, in diencephalon ; nucleus Darkschewitsch, interstitial nucleus of the medial logitudinal fasciculus, parabrachial nucleus, locus ceruleus, Kolliker-Fuse nucleus, trigeminal mesencephalic nucleus, red nucleus, substantia nigra, nucleus of posterior commissure, Edinger-Westphal nucleus, and dorsal raphe nucleus etc, in mesencephalon ; giganto-cellular reticular nucleus, raphe magnus nucleus, raphe pallidus nucleus, raphe obscuous nucleus, nucleus of solitary tracts, lateral reticular nucleus, parvocellular reticular nucleus, area postrema, facial nucleus, pontine reticular nucleus, pontine nucleus of trigeminal nerve and spinal nucleus of trigeminal nerve etc, in rhombencephalon. There are significant difference of numbers of PRV-Ba immunoreactive cells between right and left sides of brain in almost nuclei[P< 0.05]. But PRV-Ba immunoreactive cells were observed only ipsilaterally in accessory trigeminal motor nucleus, accessory facial nucleus and agranular insular cortex. Frontal cortex was the only area which were shown contralateral immunoreactivity. The results of this study provide anatomical support that both the cranial and caudal bellies are innervated by the same upper nuclei. The results also support the suggestion that the lower nuclei of digastric muscle, accessory trigeminal motor nucleus and accessory facial nucleus consist of somatotopic motor complex.

Middle ear pressure changes before and after septoplasty

This study included 50 adult patients suffering from longstanding nasal obstruction due to septal deviation. They were divided into 2 groups: Group [A] comprised of 40 patients proved to have abnormal negative middle ear pressure [MEP] and group [B] comprised of 10 patients proved to have normal MEP [control group]. In group A, 60% of the diseased ears were found on the same side of the obstructed nasal passage. The mean MEP in the ipsilateral ear was -64.4 + 84.8 mm H20 preoperatively and following septoplasty increased significantly to -30. + 39.1 mm H20 [P <0.05]. In the contralateral ear, the mean MEP was -59 + 71.1 mm H20 preoperatively and following septoplasty increased significant to 20.2 + 37.7 mm H20 [p <0.05]. In the control group [B], all the patients exhibited no significant change in MEP in either ear following septoplasty