Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Anmeidan （AMD） on biological rhythm and related protein expression in sleep-deprived rats. MethodA total of 80 SD rats were randomized into control group （Ctrl， equivalent volume of saline）， model group （SD， equivalent volume of saline）， AMD group （9.09 g·kg-1·d-1）， and melatonin group （MT， 0.27 g·kg-1·d-1）. Insomnia was induced in rats by self-made sleep deprivation box （4 weeks）. Circadian rhythm of spontaneous activity was evaluated by spontaneous activity video analysis system. Morphology of hypothalamus was observed based on hematoxylin-eosin （HE） staining， and the histomorphology of hypothalamus neurons and the Nissl's bodies based on Nissl staining. Western blotting was employed to detect the expression of hypothalamic proteins in cAMP-response element binding protein （CREB）/clock gene period （Per） pathway， and immunohistochemistry the expression of brain and muscle ARNT-like protein 1 （Bmal1）， Clock， Per1， and cryptochrome circadian regulator 1 （Cry1）. ResultThe model group demonstrated circadian rhythm disorder， as manifested by the significant increase in activity time in 6 designated time periods compared with the control group， and the rise in the activity speed and frequency （P<0.01）. Moreover， model group showed decrease in number of neurons which were sparsely arranged with shrunken or fragmented nuclei， reduction in number and loss of Nissl's bodies with light color， and drop in the relative expression of p-CREB and Per1， and the positive rate of Bmal1， Clock， Per1， and Cry1 （P<0.01）. Compared with model group， AMD group demonstrated reduction in time， speed， and frequency of activity （P<0.01）. Moreover， the AMD group also showed alleviation of neuronal damage （P<0.01）， and increase in the number of neurons with clear nuclei and cytoplasm in some， and the number of Nissl's bodies. AMD raised the expression of p-CREB and Per1 proteins， and the positive rate of Bmal1， Clock， Per1， and Cry1 （P<0.01）. ConclusionAMD ameliorated spontaneous circadian rhythm of sleep-deprived rats by regulating CREB/Per signaling pathway and further increasing the expression of Bmal1， Clock， Per1， and Cry1.

Relationship between circadian rhythm related brain dysfunction and bipolar disorder / 南方医科大学学报

OBJECTIVE@#To investigate the changes of functional connectivity (FC) in the suprachiasmatic nucleus (SCN) of patients with bipolar disorder and perform a cluster analysis of patients with bipolar disorder based on FC.@*METHODS@#The study recruited 138 patients with bipolar disorder (BD) diagnosed according to the 4th edition of Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) and 150 healthy control subjects. All the participants underwent resting-state functional magnetic resonance brain scans. DPARSF software was used to generate the FC diagram of the SCN. Based on the FC data, principal components analysis (PCA) and k-means in scikit-learn 0.20.1 were used for cluster analysis of the patients with bipolar disorder.@*RESULTS@#Compared with the healthy controls, the patients showed enhanced functional connections between the SCN and the paraventricular nucleus and between the SCN and the dorsomedial hypothalamus nucleus. Based on these FC values, the optimal cluster of unsupervised k-means machine learning for bipolar disorder was 2, and the Silhouette coefficient was 0.49.@*CONCLUSIONS@#Patients with bipolar disorder have changes in the FC of the SCN, and the FC of the rhythm pathway can divide bipolar disorder into two subtypes, suggesting that biological rhythm is one of the potential biomarkers of bipolar disorder.

Manual Acupuncture Stimulation of Paired Acupoints Can Relieve Sleep Disorder Possibly by Upregulating Pineal Melatonin Protein and Its Receptor mRNA Levels in the Suprachiasmatic Nucleus in Insomnia Rats / 针刺研究

OBJECTIVE: To observe the effect of manual acupuncture stimulation of paired "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non-acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) mRNAs in insomnia rats, so as to explore their action difference and the underlying mechanism in improving insomnia. METHODS: Male SD rats were randomly divided into normal control (n=12), mo-del (n=8), GV 20+HT 7(n=12), GV 20+SP 6(n=11), and GV 20+ non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of Para-chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days. The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the midpoint between the elbow-tip and armpit on the medial side of the upper-arm) were punctured with filiform needles and manipulated by rotating the needle for about 1 min which was repeated once again every 10 min during 30 minutes' needle-retaining. The treatment was conducted once daily for 7 days. The expression levels of MT immunoactivity in the conarium tissue, and MT1 and MT2 mRNAs of the suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and fluorescence quantitative real time-PCR, respectively. RESULTS: After modeling, the expression levels of pineal MT (an increase of gray value means a decrease of immunoactivity), SCN MT1 and MT2 mRNAs were notably down-regulated in the model group relevant to the normal control group (P0.05). CONCLUSION: Manual acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep disorder in insomnia rats, which may be related to its effects in increasing the levels of pineal MT protein, and MT1 and MT2 mRNAs in hypothalamic SCN.

Electroacupuncture Intervention Regulates Circadian Rhythms by Down-regulating Per Gene Expression in Hypothalamic Suprachiasmatic Nucleus of Hepatocellular Carcinoma Mice / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the rhythm of running-wheel activity of hepatocellular carcinoma (HCC) mice and the expression of Per 1 and Per 2 (circadian rhythm genes) in the hypothalamic suprachiasmatic nucleus (SCN), so as to investigate its mechanism underlying regulating circadian rhythm. METHODS: A total of 108 male C 57 BL / 6 J mice were randomly divided into control, HCC model and EA groups which were further assigned to six zeitbeger (environmental light-dark cycle) time (ZT) point (ZT 0, ZT 4, ZT 8, ZT 12, ZT 16 and ZT 20) subgroups. The HCC model was established by injection of H 22 cancer cell (abdominal 3rd generation, 10 µL) suspension into the larger live lobe. Mice of the control group received saline injection of the liver lobe. EA (2 Hz/15 Hz, 0.2 mA) was applied to bilateral "Ganshu" (BL 18) and "Zhiyang" (GV 9) for 15 min, once daily for 10 days. Mice of the control and model groups received the same binding-fixing to those of the EA group. Circadian running-wheel activity of 12 h∶12 h light darkness (LD) cycle (activity onset and acrophase of actogram, amplitude or peak of periodogram) was recorded by using ClockLab (ACT-500) software and analyzed by MATLAB (R 2007 b) before and after EA treatment. The pathological changes of liver cells were observed under light microscope after sectioning and H．E. staining. The expression levels of Per 1 mRNA and Per 2 mRNA in the liver tissues were determined by fluorogenic quantitative real time-PCR. RESULTS: (1) Following modeling, the amplitude of periodogram of running-wheel activity was significantly lowered at ZT 0, ZT 4, ZT 8, ZT 12, ZT 16, and ZT 20 relevant to the control group (P0.05). (2) The expression levels of Per 1 mRNA and Per 2 mRNA in the SCN were significantly up-regulated at the 6 time-points in the model group relevant to the control group (P<0.05), and obviously down-regulated at ZT 8 after EA intervention relevant to the model group (P<0.05)．. CONCLUSION: EA can benignly regulate the rhythm of running-wheel activity of HCC mice, which may be closely related to its effect in down-regulating the expression of circadian rhythm genes Per 1 and Per 2 in the SCN.

De la cronobiología a la cronomedicina / From chronobiology to chronomedicine

Resumen Los grandes avances científicos en diversas áreas biomédicas, así como sus demandas de conocimiento y dedicación, han alejado al investigador de la cama del paciente y, por su parte, el clínico poco a poco se trasforma en un técnico en atención médica, y deja de lado el conocimiento científico. Es así como nace la necesidad de unir la investigación básica y la clínica, es decir, trasladar los hallazgos del laboratorio a la medicina clínica. La medicina traslacional surge para darle continuidad a la medicina basada en evidencias, obtenidas en los laboratorios. Sin embargo, la investigación biomédica básica no se limita a la metabolómica, la proteómica, la terapia génica o a la nanotecnología, por mencionar algunas líneas de investigación; existen otras mucho más sencillas, pero no por esto menos importantes. El estudio de los ritmos biológicos es un claro ejemplo donde se ha logrado establecer el puente de transmisión y aplicación de la ciencia básica a la aplicación a problemas de salud. La cronomedicina propone un mejor entendimiento y manipulación de la fisiología, utilizando sus variaciones circadianas como parte del diagnóstico y tratamiento de algunas patologías.

Abstract The major scientific advances in various biomedical areas as well as its demands for knowledge and dedication have moved away the researcher from of the patient's bedside, and the clinician is gradually been transformed into a technician in medical care, leaving aside the scientific knowledge. Therefore the need to join the basic research and the clinic arose and to translate the findings of the laboratory to clinical medicine was born. The translational medicine appeared to give continuity to the evidence-based medicine obtained in the laboratory. However the basic biomedical research is not limited to metabolomics, proteomics, gene therapy or nanotechnology, just to mention a few research lines, some of these are much easier but are not less important. The study of biological rhythms is a clear example of successfully setting up the bridge between transmission and the application of basic science applied to health problems. The chronomedicine proposes a better understanding and manipulation of the physiology, using circadian variations as part of the diagnosis and treatment of certain pathologies.

Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

BACKGROUND: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. METHODS: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. RESULTS: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. CONCLUSION: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Controladores del tiempo y el envejecimiento: núcleo supraquiasmático y glándula pineal / Aging process entrainment: suprachiasmatic nucleus and pineal gland

El núcleo supraquiasmático (NSQ) es el principal reloj biológico de los mamíferos y sincroniza la actividad de la glándula pineal al ciclo luz-oscuridad a través de una vía polisináptica. El efecto de asa de retroalimentación neuroendocrina se lleva a cabo por la melatonina. El presente trabajo pretende demostrar que la glándula pineal modula la sensibilidad a la luz en el NSQ. Se utilizaron ratas Wistar, y se asignaron a 3 grupos: grupo A (falsa pinealectomía -sham-, sin luz), grupo B (falsa pinealectomía -sham- + luz) y grupo C al cual se le realizó la pinealectomía + luz, después de la manipulación se sacrifican para realizar inmunohistoquímica para c-Fos y al final conteo celular por técnica de estereología. Se obtuvo una reducción del 46,8% del promedio de células inmunorreactivas a c-Fos en el grupo C en comparación del grupo B. Este trabajo muestra que la sensibilidad a la luz está modulada por la actividad de la glándula pineal.

The suprachiasmatic nucleus (SCN) is the main and major biological clock in mammals and is responsible for the synchronization of the pineal gland to the light/darkness cycle through a polysynaptic pathway. The neuroendocrine feedback loop effect is carried out by melatonin. This study was carried out to demonstrate that the pineal gland adjusts the sensibility to light in the suprachiasmatic nucleus. Wistar rats were allocated in 3 groups: Group A (sham pinalectomy, without light), group B (sham pinealectomy + light) and group C which underwent real pinalectomy + light. After the intervention the animals were slain to perform immunohistochemistry for c-Fos and cell counting by stereology technique. A 46.8% average reduction in c-Fos immunoreactive cells was achieved in-group C as compared with group B. The present work shows that sensibility to the light is modulate by the activity of the pineal gland.

Changes in the suprachiasmatic nucleus during aging: implications for biological rhythms

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN...

Central nervous regulation of spleen function: New insights from animal studies.

The spleen is located in the upper left quadrant of the abdomen. It has two main functions that is acting as part of the immune system and as a filter. The spleen has a thin connective tissue capsule from which short septa extend inwards. These septa are, in turn, connected to a complex reticulin framework.There are two distinct components of the spleen, the red pulp and the white pulp. The red pulp consists of large numbers of sinuses and sinusoids filled with blood and is responsible for the filtration function of the spleen. The splenic venomotor fibres join the left phrenic nerve in the mid-cervical region. Coursing with it as non-medullated fibres, they eventually perforate the diaphragm, where for a time they accompany the inferior phrenic artery. Deviating towards the celiac ganglion, they next join company with the splenic vein, and are eventually distributed to localised parts of the vein. This review article evaluates the conventional knowledge and points to new insights into neural regulation of spleen.

Envejecimiento de un reloj (cronobiología de la vejez) / Ageing of a clock (cronobiology of old age)

El envejecimiento es el conjunto de modificaciones morfológicas y fisiológicas generadas como consecuencia de la acción del tiempo sobre los seres vivos. Entre estas modificaciones se debe de incluir la incapacidad de adaptación y de responder a los cambios medioambientales, por cada uno de los órganos, aparatos y sistemas. El envejecimiento de los organismos, y particularmente del hombre, es motivo de preocupación desde hace años debido a que nuestra expectativa de vida ha aumentado significativamente y este hecho ha acrecentado el número de habitantes con problemas de envejecimiento, que presentan procesos de deterioro paulatino de órganos y sus funciones asociadas. Muchas enfermedades, entre ellas ciertos tipos de demencia, enfermedades articulares, cardíacas y algunos tipos de cáncer, han sido asociados al proceso de envejecimiento. Uno de los trastornos más notorios en la senectud es la alteración del ritmo de sueño-vigilia, reflejo de un mal funcionamiento del reloj biológico y en consecuencia del sistema circadiano. En este escrito se abordan las bases fisiológicas de la desincronización interna que sufre el hombre en edad adulta así como sus consecuencias fisiológicas y algunas recomendaciones para coadyuvar al tratamiento de este trastorno.

Aging is the set of morphological and physiological changes generated by the action of time on living beings. These changes include the inability to adapt and respond to environmental challenges, by organs, apparatus and systems. Aging of organisms and particularly of man, has become a concern in recent years, because our life expectancy has increased significantly and this has increased the number of individual ailing from the effects of aging, which includes a series of processes of gradual deterioration of organs and their associated functions. Many diseases, such as dementia, joint disease, cardiovascular disease and some cancers have been associated with the aging process. One of the most notorious disorders in aged people is the alteration of the sleep-wake rhythm, a reflection of a malfunctioning biological clock and thus of the circadian system. This manuscript addresses the physiological basis and consequences of internal desynchronization suffered by aged people and numbers recommendations for the treatment of this disorder.

Serotonin and circadian rhythms

All mammal behaviors and functions exhibit synchronization with environmental rhythms. This is accomplished through an internal mechanism that generates and modulates biological rhythms. The circadian timing system, responsible for this process, is formed by connected neural structures. Pathways receive and transmit environmental cues to the central oscillator, the hypothalamic suprachiasmatic nucleus, which mediates physiological and behavioral alterations. The suprachiasmatic nucleus has three major inputs: the retinohypothalamic tract (a direct projection from the retina), the geniculohypothalamic tract (an indirect photic projection originating in the intergeniculate leaflet), and a dense serotonergic plexus from the raphe nuclei. The serotonergic pathway, a source of non-photic cues to the suprachiasmatic nucleus, modulates its activity. The importance of raphe nuclei in circadian rhythms, especially in photic responses, has been demonstrated in many studies. Serotonin is the raphe neurotransmitter that triggers phase shifts, inhibits light-induced phase-shifts, and plays a role in controlling the sleep-wake cycle. All data to date have demonstrated the importance of the raphe, through serotonergic afferents, in adjusting circadian rhythms and must therefore be considered a component of the circadian timing system. The aim of this paper is to review the literature addressing the involvement of serotonin in the modulation of circadian rhythm

Suprachiasmatic nucleus slices induce molecular oscillations in fibroblasts / 中华行为医学与脑科学杂志

Objective To study whether suprachiasmatic nucleus (SCN) slices are able to induce the molecular oscillations in NIH/3T3 fibroblast. Methods SCN slices from 10-day-old SD rat and NIH/3T3 cells were co-cultured in a serum-free condition. 24h mRNA profiles of Per1 and Rev-Erbα were measured in NIH/3T3 cells using real-time PCR. Results After co-cultured for 6 days, ten SCN slices can induce the significant daily oscillation of Per1 and Rev-Erba mRNA expression in NIH/3T3 cells (P<0.01). The peak time Rev-erbα and Per1 were at CT5 and CT11 respectively. Rev-Erbα oscillations were significant even with two SCN slices and 2 days co-culture (P<0.05). In contrast, Per1 expression fluctuation was not observed until more than 6 days of co-culture and with six SCN slices (P=0.031). Conclusion Diffusible signals release from SCN slices can regulate molecular rhythms in cultured fibroblasts. Rev-Erbα and Per1 don't start to oscillate at the same time, and Rev-Erbα is more sensitive to SCN signal.

Morphological Changes in Vasopressin-immunoreactive Neurons in the Hypothalamus of the Aged Rats / 체질인류학회지

The role of neuropeptides in the central nervous system (CNS) has received increasing attention. Numerous peptide molecules are found in the mammalian CNS and many of them are thought to act as either neurotransmitters or neuromodulators. The neuropeptides found in high concentration in the hypothalamus include vasopressin (VP), vasoactive intestinal polypeptide, somatostatin, and oxytocin. The main approches to assess the involvement of neuropeptides can be focused on functions affecting the aging of the brain. Morphological aging of the CNS has been characterized by degenerative changes of fiber connections and cell loss, although degeneration does not always occur to the same extent throughout various parts of the brain and, moreover, varies for different cell types. Despite of many studies in VP containing neurons , there exist discrepancies in results about the changes of aged rat brain. The aim of the present study is, therefore, to investigative possible changes in the number and morphology of VPimmunoreactive neurons with aging in each area of the hypothalmus of the aged rats. As a result, the number of VP-immunoreactive neurons was decreased in hypothalamus nucleus of aged group. Especially, in VP-immunoreactive neurons of hypothalamus, the size of neuronal cell body and nuclei in aged group is larger than in young group and the fiber density of immunoreactivity neurons of median eminance (ME) in aged group is stronger than in young group. But, the total number of VP-immunoreactive neurons in the suprachiasmatic nucleus (SCN) of the aged group is larger than in the young group. These studies indicate the involvement of VP-immunoreactive neurons in aging process of hypothalamus, and aging process may affect the synthesis of VP in the neurons of hypothalamic nuclei. Whereas, in VP expression, aging process induces an enlargement of the cell size of surviving neurons to compensate.

Reactivation of metabolically impaired neurons in Alzheimer’s disease

Several lines of evidence show that decreased metabolic rate precedes cognitive impairment in Alzheimer ’s disease (AD). Decreased neuronal metabolism contributes to neuronal atrophy and functional impairment and is thus an early occurring hallmark of AD. Factors that may contribute to a diminishment in neuronal metabolism are age, sex, APOE-ε 4 and decreased levels of sex hormones or melatonin. Several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon we paraphrased as “use it or lose it”. Moreover, a number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may to a certain degree restore several aspects of cognition and other central functions. For instance, the circadian system of Alzheimer patients may be restimulated by exposing them to more light or transcutaneous nerve stimulation. A procedure allowing testing of the efficacy of putative stimulatory compounds such as neurotrophins and precursor cells has been developed in order to be able to culture human postmortem brain tissue.

Changes in orexin-A and neuropeptide Y expression in the hypothalamus of the fasted and high-fat diet fed rats

This study was aimed to investigate the changes of orexin-A (OXA) and neuropeptide Y (NPY) expression in the hypothalamus of the fasted and high-fat diet fed rats. For the experiments, the male Sprague-Dawley (SD) rats were used as the model of high-fat diet-induced obesity. The mean loss of body weight (MLBW) did not show the linear pattern during the fasting; from 24 h to 84 h of fastings, the MLBW was not significantly changed. The numbers of OXA-immunoreactive (IR) neurons were decreased at 84 h of fasting compared with those in other five fasting subgroups. The NPY immunoreactivities in the arcuate nucleus (ARC) and the suprachiasmatic nucleus (SCN) observed at 84 h of fasting were higher than that observed at 24 h of fasting. The number of OXA-IR neurons of the LHA (lateral hypothalamic area) in the high-fat (HF) diet fed group was more increased than that of the same area in the normal-fat (NF) diet fed group. The NPY immunoreactivities of the ARC and the SCN were higher in HF group than those observed in the same areas of NF group. Based on these results, it is noteworthy that the decrease of the body weight during the fast was not proportionate to the time-course, implicating a possible adaptation of the body for survival against starvation. The HF diet might activate the OXA and the NPY in the LHA to enhance food intake.

A study on the expression of immediate-early genes by light stimuli in the rat suprachiasmatic nucleus using differential display / 대한해부학회지

The hypothalamic suprachiasmatic nucleus (SCN) of the mammal is the circadian pacemaker responsible for generation of circadian rhythms. Several immediate-early genes are expressed in the SCN by light stimuli which induce phase shifts of animal activity rhythms. By using differential display-polymerase chain reaction, we investigated expression of several immediate-early genes in the light-stimulated SCN. In addition, we analyzed the light-induced expression changes of two known immediate-early genes, Arc and Rheb, in the SCN. We have screened and cloned 25 differentially expressed genes in the SCN, and identified a gene, a rat homologue of A6 kinase, which expression was regulated by light stimuli. One hour light stimuli during the subjective night dramatically induced the gene expression in the SCN, whereas light stimuli during the subjective light phase did not. This finding implies that a rat homolgue of A6 kinase may be involved in the photic entrainment of the circadian clock. On the other hand, Arc and Rheb mRNA expressions were not increased in the SCN by light stimuli.

Immunocytochemical Study on the Monoaminergic Innervation of Diencephalic Visual Structures in the Squirrel Monkey

This study was for investigating relations between distributions of monoamines-norepinephrine, serotonin, and dopamine-on the visual system and their functions. Distributions of these monoamines in the lateral geniculate body, pulvinar, lateral posterior nucleus, and suprachiasmatic nucleus were investigated. Brain of a squirrel monkey was removed and frozen sectioned. Immunocytochemical study was performed for the tissue of the brain. Results showed that the anterior part of the lateral geniculate body contained more monoamines than the posterior part. More serotonins were distrbuted at the magnocellular part, and more dopamines were found at the parvocellular part. In pulvinar, more norepinephrines were distributed at the medial part, while serotonins were evenly distributed at all parts. In lateral posterior nucleus and suprachiasmatic nucleus, three kinds of monoamines were distributed with high density. Among the three, density of the serotonin showed the highest value. The lateral geniculate body relates with visual perception such as visual acuity, form and color perception, and stereopsis, while the pulvinar relates with visual functions, such as visual attention, sensory integration, and differentiation. Since norepinephrine and serotonine are distributed with high density in the pulvinar than in the lateral geniculate body those two monoamines are expected to playa major role for visual functions. Inferior part of the pulvinar relates with visual imagination, and the lateral posterior nucleus relates with integration of visual sensory. Relatively high distribution of dopamine in these two parts means that dopamine may playa major role for visual imagination and integration. As suprachiasmatic nucleus relates with controlling biorhythm, dense distribution of monoamines in suprachiasmatic nucleus implies that the monoamines may work for controlling biorhythm.