D1- and D2-type dopamine receptors are immunolocalized in pial and layer I astrocytes in the rat cerebral cortex.

Pial astrocytes, a cellular component of the cerebral cortex surface structure, are observed in a wide range of mammalian species. Despite being recognized as such, the functional potential of pial astrocytes has long been overlooked. Our previous research demonstrated that pial astrocytes exhibit stronger immunoreactivity for muscarinic acetylcholine receptor M1 than protoplasmic astrocytes, indicating sensitivity to neuromodulators.

An Open-label Phase I/IIa Clinical Trial of 11β-HSD1 Inhibitor for Cushing's Syndrome and Autonomous Cortisol Secretion.

Context: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) patients.

Objective: To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients.

Design: A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database.

Immunolocalization of muscarinic M1 receptor in the rat medial prefrontal cortex.

The medial prefrontal cortex (mPFC) has been considered to participate in many higher cognitive functions, such as memory formation and spatial navigation. These cognitive functions are modulated by cholinergic afferents via muscarinic acetylcholine receptors. Previous pharmacological studies have strongly suggested that the M1 receptor (M1R) is the most important subtype among muscarinic receptors to perform these cognitive functions.

Neurotransmitters and neuropeptides in gonadal steroid receptor-expressing cells in medial preoptic area subregions of the male mouse.

Testosterone is involved in male sexual, parental and aggressive behaviors through the androgen receptor (AR) and estrogen receptor (ER) α expressed in the brain. Although several studies have demonstrated that ERα and AR in the medial preoptic area (MPOA) are required for exhibiting sexual and aggressive behaviors of male mice, the molecular characteristics of ERα- and AR-expressing cells in the mouse MPOA are largely unknown. Here, we performed in situ hybridization for neurotransmitters and neuropeptides, combined with immunohistochemistry for ERα and AR to quantitate and characterize gonadal steroid receptor-expressing cells in the MPOA subregions of male mice.

Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala.

The brain shows various sex differences in its structures. Various mammalian species exhibit sex differences in the sexually dimorphic nucleus of the preoptic area (SDN-POA) and parts of the extended amygdala such as the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr) and posterodorsal part of the medial amygdala (MePD). The SDN-POA and BNSTpr are male-biased sexually dimorphic nuclei, and characterized by the expression of calbindin D-28K (calbindin 1).

Quantitative analysis of axon collaterals of single pyramidal cells of the anterior piriform cortex of the guinea pig.

Background: The role of the piriform cortex (PC) in olfactory information processing remains largely unknown. The anterior part of the piriform cortex (APC) has been the focus of cortical-level studies of olfactory coding, and associative processes have attracted considerable attention as an important part in odor discrimination and olfactory information processing. Associational connections of pyramidal cells in the guinea pig APC were studied by direct visualization of axons stained and quantitatively analyzed by intracellular biocytin injection in vivo.

Acylated Glycosidic Acid Methyl Esters Generated from the Convolvulin Fraction of Rhizoma Jalapae Braziliensis by Treatment with Indium(III) Chloride in Methanol.

Four hexaglycosides of methyl 3S,12S-dihydroxyhexadecanoate (1-4) were provided after treatment of the crude convolvulin fraction from Rhizoma Jalapae Braziliensis (the root of Ipomoea operculata (GOMES) MART., Convolvulaceae) with indium(III) chloride in methanol. The structures of 1-4 were elucidated on the basis of spectroscopic and chemical methods.

High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity.

Objective: High-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself.

Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes.

The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH) has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1)-deficient mice, are not consistent with each other.

A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata.

Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus.

Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases.

Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior. These neurons form neural circuits to integrate different modalities of behavioral and environmental factors, such as stress, maternal care, and feeding conditions. One possible mechanism for integrating environmental factors through the monoaminergic and neuropeptidergic neurons is through the epigenetic regulation of gene expression via altered acetylation of histones.

Disruption of Stard10 gene alters the PPARα-mediated bile acid homeostasis.

STARD10, a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) protein family, is highly expressed in the liver and has been shown to transfer phosphatidylcholine. Therefore it has been assumed that STARD10 may function in the secretion of phospholipids into the bile. To help elucidate the physiological role of STARD10, we produced Stard10 knockout mice (Stard10(-/-)) and studied their phenotype.

Spinal mechanism underlying the antiallodynic effect of gabapentin studied in the mouse spinal nerve ligation model.

We studied the antiallodynic effect of gabapentin (GBP) in the mouse model of neuropathic pain, aiming at clarifying the underlying mechanism. The L5 spinal nerve ligation induced tactile allodynia, an increase of CD11b expression, and an increase in the protein expression level of the voltage-dependent Ca(2+) channel α(2)/δ-1 subunit in the spinal dorsal horn on the injured side. The chronic intrathecal administration of GBP (100 µg/body per day) as well as ω-conotoxin MVIIA, an N-type Ca(2+)-channel blocker, completely suppressed allodynia, but did not attenuate the CD11b expression.

Fasting and high-fat diet alter histone deacetylase expression in the medial hypothalamus.

Increasing attention is now being given to the epigenetic regulation of animal and human behaviors including the stress response and drug addiction. Epigenetic factors also influence feeding behavior and metabolic phenotypes, such as obesity and insulin sensitivity. In response to fasting and high-fat diets, the medial hypothalamus changes the expression of neuropeptides regulating feeding, metabolism, and reproductive behaviors.

Dopamine D5 receptor immunoreactivity is differentially distributed in GABAergic interneurons and pyramidal cells in the rat medial prefrontal cortex.

In the rodent neocortex, the dopamine D5 receptor (D5R) appears to be the predominant subtype of D1-like receptors that are generally considered to play important roles in cognitive functions subserved by the prefrontal cortex (PFC). In this study, to identify the precise localization of D5R in rat PFC, we used a receptor-specific antibody and observed the immunolabeled structures by light and confocal laser scanning microscopies. D5R immunolabeling was found in nearly all neurons, both excitatory and inhibitory neurons.

Synaptic characteristics between cortical cells in the rat prefrontal cortex and axon terminals from the ventral tegmental area that utilize different neurotransmitters.

Projections from the ventral tegmental area (VTA) have been demonstrated to terminate in the prefrontal cortex (PFC) and to be dopaminergic and/or gamma-aminobutyric acidergic (GABAergic), forming a neural circuit implicated in certain memory and cognitive processes. However, it has not been determined whether gamma-aminobutyric acid (GABA) and dopamine (DA) are localized in certain types of axon terminals from the VTA to the PFC. To determine the synaptic characteristics made by postsynaptic prefrontal cortical structures and mesoprefrontal fibers utilizing either GABA or DA, we performed a double-labeling method for electron microscopy, in which we combined peroxidase markers for anterograde tract-tracing with postembedding immunogold labeling for tyrosine hydroxylase, DA, and GABA in rats.

Immunolocalization of muscarinic receptor subtypes in the reticular thalamic nucleus of rats.

In this study, to identify the precise localization of the muscarinic receptor subtypes m2, m3 and m4 in the rostral part of the rat reticular thalamic nucleus (rRt), namely, the limbic sector, we used receptor-subtype-specific antibodies and characterized the immunolabeled structures by light, confocal laser scanning, and electron microscopies. The m2-immunolabeling was preferentially distributed in the distal dendrite region where cholinergic afferent fibers tend to terminate and in the peripheral region of somata, whereas the m3-immunolabeling was more preferentially distributed in a large part of somata and in proximal dendrite shafts than in the distal dendrite region. Dual-immunofluorescence experiments demonstrated that majority of rRt neurons with parvalbumin immunoreactivity contain both m2 and m3.

Quantitative analysis of axon collaterals of single superficial pyramidal cells in layer IIb of the piriform cortex of the guinea pig.

To understand the functional organization of the piriform cortex (PC), the axon collaterals of three pyramidal cells in layer IIb of the anterior PC and one pyramidal cell in layer IIb of the posterior PC were labeled and quantitatively analyzed by intracellular biocytin injection in the guinea pig. Single pyramidal cells in the anterior and posterior PCs have widely distributed axon collaterals, which exhibit little tendency for patchy concentrations inside as well as outside the PC. The total lengths of the axon collaterals of the three fully analyzed pyramidal cells ranged from 68 to 156 mm, more than 50% of which were distributed in the PC.

Thalamocortical projection from the ventral posteromedial nucleus sends its collaterals to layer I of the primary somatosensory cortex in rat.

Here we examined quantitatively axonal projections originating from the ventral posteromedial thalamic nucleus (VPM) to layer I of the primary somatosensory cortex (SI) by extracellular and intracellular injections of biocytin as an anterograde tracer. Following the extracellular injections, two types of VPM afferents with different arborization patterns in SI were observed. The type I extended vertically, forming dense plexus in layers IV and VI, and projected collaterals to layer I.

Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and gamma-aminobutyric acidergic cortical cells in the prelimbic cortex of the rat.

Although the reciprocal interconnections between the prefrontal cortex and the mediodorsal nucleus of the thalamus (MD) are well known, the involvement of inhibitory cortical interneurons in the neural circuit has not been fully defined. To address this issue, we conducted three combined neuroanatomical studies on the rat brain. First, the frequency and the spatial distribution of synapses made by reconstructed dendrites of nonpyramidal neurons were identified by impregnation of cortical cells with the Golgi method and identification of thalamocortical terminals by degeneration following thalamic lesions.

Antiemetic effect of dexamethasone on cisplatin-induced early and delayed emesis in the pigeon.

We investigated the ability of dexamethasone to attenuate cisplatin (4 mg/kg, i.v.)-induced early and delayed emesis.

Quantitative analysis of axon collaterals of single cells in layer III of the piriform cortex of the guinea pig.

Recent physiological and morphological studies suggest that the piriform cortex (PC) functions like the association areas of the neocortex rather than the typical primary sensory area as was previously assumed. The axon connection patterns of single cells are important for understanding the functional organization of the PC. The axon collaterals of three single pyramidal cells and one spiny multipolar cell in layer III of the PC were labeled and quantitatively analyzed by intracellular injections of biocytin in guinea pigs.

Antiemetic effect of a tachykinin NK1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon.

Cisplatin (4 mg/kg, i.v.) induced both early emesis, which appears within the first 8-h period, and delayed emesis, which appears between 8 and 48 h after its administration to pigeons.

Ultrastructure of ascending cholinergic terminals in the anteroventral thalamic nucleus of the rat: a comparison with the mammillothalamic terminals.

In this study, to identify the ultrastructure and distribution of ascending cholinergic afferent terminals in the anteroventral thalamic nucleus, we used an anti-vesicular acetylcholine transporter antibody as marker of cholinergic afferents, and characterized the immunoreactive terminals at the ultrastructural level. We then compared the distribution pattern of the cholinergic terminals and that of the mammillothalamic terminals identified by anterograde transport of a tracer injected into the mammillary body. The cholinergic terminals were small, and formed both symmetrical and asymmetrical synaptic contacts throughout the dendritic arborizations, particularly in the distal region.