A diffusion barrier between the area postrema and nucleus tractus solitarius.

The blood-brain barrier (BBB) is a structural and functional barrier that prevents free exchange of circulating substances with the brain, where the endothelial cells of microvessels are joined by tight junctions. The circumventricular organs (CVOs), by contrast, lack tight junctions and exhibit more direct communication with the circulating blood and cerebrospinal fluid. Despite many outstanding morphological studies at the electron microscopic level, there remain misconceptions that the CVOs provide direct passage of blood-borne substances to the rest of the brain.

Synaptic relationships between proopiomelanocortin- and ghrelin-containing neurons in the rat arcuate nucleus.

Both proopiomelanocortin (POMC) and ghrelin peptides are implicated in the feeding regulation. The synaptic relationships between POMC- and ghrelin-containing neurons in the hypothalamic arcuate nucleus were studied using double-immunostaining methods at the light and electron microscope levels. Many POMC-like immunoreactive axon terminals were found to be apposed to ghrelin-like immunoreactive neurons and also to make synapses with ghrelin-like immunoreactive neuronal perikarya and dendritic processes.

Synaptic interaction between ghrelin- and ghrelin-containing neurons in the rat hypothalamus.

Synaptic relationships between ghrelin-like immunoreactive axon terminals and other neurons in the hypothalamic arcuate nucleus (ARC) were studied using immunostaining methods at the light and electron microscope levels. Many ghrelin-like immunoreactive axon terminals were found to be in apposition to ghrelin-like immunoreactive neurons at the light microscopic level. At the electron microscopic level, ghrelin-like immunoreactive axon terminals were found to make synapses on ghrelin-like immunoreactive cell bodies and dendrites in the ARC.

Neural interaction between galanin-like peptide (GALP)- and luteinizing hormone-releasing hormone (LHRH)-containing neurons.

Galanin-like peptide (GALP), commonly known as an appetite-regulating peptide, has been shown to increase plasma luteinizing hormone (LH) through luteinizing hormone-releasing hormone (LHRH). This led us to investigate, using both light and electron microscopy, whether GALP-containing neurons in the rat brain make direct inputs to LHRH-containing neurons. As LHRH-containing neurons are very difficult to demonstrate immunohistochemically with LHRH antiserum without colchicine treatment, we used a transgenic rat in which LHRH tagged with enhanced green fluorescence protein facilitated the precise detection of LHRH-producing neuronal cell bodies and processes.

Characterization of orexin A immunoreactivity in the rat area postrema.

The distribution of orexin A immunoreactivity and the synaptic relationships of orexin A-positive neurons in the rat area postrema were studied using both light and electron microscopy techniques. At the light microscope level, numerous orexin A-like immunoreactive fibers were found within the area postrema. Using electron microscopy, immunoreactivity within fibers was confined primarily to the axon terminals, most of which contained dense-cored vesicles.

Electron microscopy examination of galanin-like peptide (GALP)-containing neurons in the rat hypothalamus.

Galanin-like peptide (GALP) is a novel peptide which is isolated from the porcine hypothalamus. GALP-containing neurons are present in the arcuate nucleus (ARC), being particularly densely concentrated in medial posterior regions. To observe the ultrastructure and synaptic relationships of GALP-containing neurons in the ARC, light and immunoelectron microscopy techniques were used.

State-dependent effects of orexins on the serotonergic dorsal raphe neurons in the rat.

The serotonergic dorsal raphe (DR) neurons play an important role in sleep-wakefulness regulation. Orexinergic neurons in the lateral hypothalamus densely project to the brainstem sites including the DR. To test the effects of orexins on the serotonergic DR neurons, we applied orexin A (0.

The orexinergic synaptic innervation of serotonin- and orexin 1-receptor-containing neurons in the dorsal raphe nucleus.

Orexin/hypocretin has been well demonstrated to excite the serotonergic neurons in the dorsal raphe nucleus (DRN). We studied the morphological relationships between orexin-containing axon terminals and serotonin- as well as orexin-receptor-containing neurons in the dorsal raphe nucleus. Using immunohistochemical techniques at the light microscopic level, orexin A (OXA)-like immunoreactive neuronal fibers in the DRN were found to make close contact with serotonergic neurons, while some of the serotonergic neurons also expressed the orexin 1 receptor (OX1R).

Galanin-like peptide in the brain: effects on feeding, energy metabolism and reproduction.

The hypothalamus plays an important role in the regulation of feeding behavior, energy metabolism and reproduction. A novel peptide containing 60 amino acid peptide and a non-amidated C-terminus is produced in the hypothalamic arcuate nucleus (ARC) and has been named galanin-like peptide (GALP) on the basis of a portion of this peptide being homologous with galanin. It acts in the central nervous system (CNS), where it is involved in the regulation of feeding behavior.

Ultrastructure of orexin-1 receptor immunoreactivities in the spinal cord dorsal horn.

The ultrastructural properties of orexin 1-receptor-like immunoreactive (OX1R-LI) neurons in the dorsal horn of the rat spinal cord were examined using light and electron microscopy techniques. At the light microscopy level, the most heavily immunostained OX1R-LI neurons were found in the ventral horn of the spinal cord, while some immunostained profiles, including nerve fibers and small neurons, were also found in the dorsal horn. At the electron microscopy level, OX1R-LI perikarya were identified containing numerous dense-cored vesicles which were more heavily immunostained than any other organelles.

Synaptic interactions between ghrelin- and neuropeptide Y-containing neurons in the rat arcuate nucleus.

Morphological relationships between neuropeptide Y- (NPY) like and ghrelin-like immunoreactive neurons in the arcuate nucleus (ARC) were examined using light and electron microscopy techniques. At the light microscope level, both neuron types were found distributed in the ARC and could be observed making contact with each other. Using a preembedding double immunostaining technique, some NPY-immunoreactive axon terminals were observed at the electron microscope level to make synapses on ghrelin-immunoreactive cell bodies and dendrites.

Hypothalamic neuronal networks and feeding-related peptides involved in the regulation of feeding.

The hypothalamus is a region of the brain that plays a critical role in feeding regulation. It has been revealed by various physiological experiments that the feeding-regulating center is confined to the ventromedial hypothalamus, lateral hypothalamus (LH) and arcuate nucleus (ARC). Many kinds of neurons in these areas of the hypothalamus express factors such as melanin-concentrating hormone (MCH), neuropeptide Y (NPY), proopiomelanocortin (POMC), orexin (OX) and ghrelin, which have been implicated in feeding regulation.

Immunoelectron microscopic examination of orexin-like immunoreactive fibers in the dorsal horn of the rat spinal cord.

The ultrastructure and synaptic relationships of orexin A-like immunoreactive neuronal fibers in the dorsal horn of the rat cervical spinal cord were examined at both the light and electron microscopic levels. At the light microscopic level, many intensely immunostained orexin A-like fibers were found, while at the electron microscopic level, immunoreactivity in these fibers was mostly confined to axon terminals. Most of the axon terminals contained dense-cored vesicles.

Electron microscopic examination of the orexin immunoreactivity in the dorsal raphe nucleus.

The ultrastructure and the synaptic relationships of the orexin-A-like immunoreactive fibers in the dorsal raphe nucleus were examined with an immunoelectron microscopic method. At the electron microscopic level, most of the immunoreactive fibers, a varicosity appearance at the light microscopic level, were found as axon terminals. The large dense-cored vesicles contained in the immunoreactive axon terminals were the most intensely immunostained organellae.

Co-existence of leptin- and orexin-receptors in feeding-regulating neurons in the hypothalamic arcuate nucleus-a triple labeling study.

The arcuate nucleus (ARC) of the hypothalamus has been identified as a prime feeding regulating center in the brain. Several feeding regulating peptides, such as neuropeptide Y (NPY) and proopiomelanocortin (POMC), are present in neurons of the ARC, which also serves as a primary targeting site for leptin, a feeding inhibiting hormone secreted predominantly by adipose tissues, and for orexin (OX)-containing neurons. OX is expressed exclusively around the lateral hypothalamus, an area also established as a feeding regulating center.

Morphological evidence of endomorphin as an agonist for the mu-opioid receptor in the rat spinal cord.

Endomorphin 2 is a newly discovered peptide that has high affinity and specificity for the mu-opioid receptor. One criterion for establishing that endomorphin serves as an endogenous agonist for the mu receptor is that it be anatomically distributed in close proximity to that receptor. We tested this idea with a preembedding double immunostaining technique to study synaptic relationships between them.

Ghrelin-induced food intake is mediated via the orexin pathway.

The hypothalamus regulates energy intake by integrating the degree of starvation or satiation with the status of the environment through a variety of neuronal and blood-derived signals. Ghrelin, a peptide produced in the stomach and hypothalamus, stimulates feeding and GH secretion. Centrally administered ghrelin exerts an orexigenic activity through the neuropeptide Y (NPY) and agouti-related protein systems.

Morphological studies of the endomorphinergic neurons in the central nervous system.

Endomorphins (EMs) are newly found endogenous opioid peptides. Both endomorphin-1 (EM-1) and -2 (EM-2) are composed of four amino acids. Their high affinity and specificity for mu-opioid receptors have been confirmed by many physiological and pharmacological studies.

Ultrastructural localization of orexin-1 receptor in pre- and post-synaptic neurons in the rat arcuate nucleus.

The distribution and ultrastructural localization of the orexin-1 receptor (OX(1)R) in the rat arcuate nucleus were studied using immunocytochemical techniques. OX(1)R-containing neurons were found throughout the nucleus, but were concentrated in its posterior region. Both OX(1)R-positive perikarya and dendrites were found to receive synapses from other unknown axon terminals.

Orexin-1 receptor immunoreactivity in chemically identified target neurons in the rat hypothalamus.

Immunohistochemistry and Western blotting were used to determine the distribution of orexin receptors in the rat brain. Strong orexin receptor 1 (OX1R) immunoreactivity was detected in the hypothalamus including the arcuate, ventromedial, and tuberomammillary nuclei that are involved in feeding regulation. The neuropeptide Y- and proopiomelanocortin-containing neurons of the arcuate nucleus, which act to stimulate or to inhibit feeding, respectively, displayed intense OX1R immunoreactivity by double immunostaining.

Orexins activate histaminergic neurons via the orexin 2 receptor.

Orexins (orexin A and B) are recently identified neuropeptides implicated in the regulation of vigilance states and energy homeostasis. We have shown here the physiological significance of histaminergic neurons in the orexin-induced arousal responses. Immunohistochemical and electron microscopic techniques revealed direct synaptic interaction between orexin-immunoreactive nerve terminals and histidine decarboxylase-immunoreactive neurons in the TMN.