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Physical exercise is a robust stimulus that enhances hippocampal neurogenesis via cell proliferation in rodents. We examined the role of systemic angiotensin (Ang) peptides in exercise-dependent enhancement of neurogenesis in the adult rat hippocampus. Plasma angiotensin peptide concentration increased rapidly in response to 30 min of treadmill exercise. After undertaking this exercise once daily for a week, the number of proliferating cells in the hippocampus, identified by 5-bromo-2'-deoxyuridine (BrdU) incorporation, had increased compared with controls. To mimic the increase in plasma Ang peptide concentrations brought about by exercise, rats were injected with 10(-5)M Ang II once daily for a week. The number of BrdU-incorporating cells and of doublecortin (DCX)-expressing immature neurons in the hippocampus rose approximately 1.5 and 1.9-fold compared with controls, respectively. The effects were completely abolished by an Ang II receptor subtype 1 antagonist losartan. These findings, taken together, suggest that an increased concentrations of Ang peptides in the systemic circulation during exercise may promote neurogenesis in the adult rat hippocampus., (Copyright © 2014 Elsevier B.V. All rights reserved.)

G-protein receptor (GPR) 40 is known to be activated by docosahexaenoic acid (DHA). However, reports studying the role and functions (including pain regulation) of GPR40 in the brain are lacking. We investigated the involvement of GPR40 in the brain on DHA-induced antinociceptive effects. Expression of GPR40 protein was observed in the olfactory bulb, striatum, hippocampus, midbrain, hypothalamus, medulla oblongata, cerebellum and cerebral cortex in the brain as well as the spinal cord, whereas GPR120 protein expression in these areas was not observed. Intracerebroventricular (i.c.v.), but not intrathecal (i.t.) injection of DHA (25 and 50μg/mouse) and GW9508 (a GPR40- and GPR120-selective agonist; 0.1 and 1.0μg/mouse) significantly reduced formalin-induced pain behavior. These effects were inhibited by pretreatment with the μ opioid receptor antagonist β-funaltrexamine (β-FNA), naltrindole (δ opioid receptor antagonist) and anti-β-endorphin antiserum. The κ opioid receptor antagonist norbinaltorphimine (nor-BNI) did not affect the antinociception of DHA or GW9508. Furthermore, the immunoreactivity of β-endorphin in the hypothalamus increased at 10 and 20min after i.c.v. injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated (at least in part) through GPR40 signaling in the supraspinal area, and may provide valuable information on a novel therapeutic approach for pain control., (Copyright © 2011 Elsevier B.V. All rights reserved.)

To elucidate the role of the preoptic area (POA) in the regulation of penile erection, we examined the effects of electrical stimulation in and around the POA on penile erection in rats, which was assessed by changes in pressure in the corpus spongiosum of the penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In unanesthetized and anesthetized rats, four types of responses were induced by stimulation in and around the POA; (1) normal type responses, which were similar to spontaneously occurring erections, characterized by slow increase in CSP pressure and sharp peaks concurrent with BS muscle bursting; (2) muscular type responses, which included sharp CSP pressure peaks (muscular component) with almost no vascular component; (3) mixed type responses, which included a sequence of high-frequency CSP peaks followed by low-frequency CSP peaks; and (4) micturition type responses, which had higher-frequency and lower-amplitude CSP peaks than other responses which were identical to those of normal micturition. In unanesthetized condition, erections were evoked by stimulation of the lateral preoptic area (LPOA), medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), reuniens thalamic nucleus (Re) and lateral septum (LS). Lower-intensity stimulation evoked erections from the LPOA, BST, PVN and RE, but not the MPOA. In anesthetized condition, stronger stimuli were required and effective sites were restricted to the LPOA, MPOA and BST. These findings suggest that the lateral and medial subdivisions of the preoptic area play different roles in mediating penile erection., (Copyright © 2010 Elsevier B.V. All rights reserved.)

To investigate the regulation mechanism of (14)C-acetate uptake in astrocytes, uptake experiments with cultured rat astrocytes were performed. In this study, we used a relatively low concentration (0.0185 mM) of (14)C-acetate. The uptake was dependent on pH and acetate concentration, and saturated by 10 mM acetate. Furthermore, the selective inhibition by p-(chloromercuri) benzenesulfonic acid (pCMBS) but not by alpha-cyano-3-hydroxycinnamate (CHC) showed that the monocarboxylate transporter-1 (MCT-1)-mediated transport system is essentially important in cultured rat astrocytes. A significant reduction (more than 30%) in (14)C-acetate uptake was observed with 0.5 mM fluorocitrate treatment, which indicated (14)C-acetate uptake in this study might reflect not only the transport process, but also the metabolic process. Glutamate significantly increased (14)C-acetate uptake. An increase in extracellular potassium concentration had no effect on (14)C-acetate uptake. The Ca(2+) ionophore A23187 caused a 40% reduction, and ouabain (inhibitor of Na(+)-K(+)-ATPase) and monensin (Na(+) ionophore) significantly decreased (14)C-acetate uptake by astrocytes. The combined use of ouabain and monensin caused significantly greater decreases than the addition of either chemical alone. These results suggest that glutamate stimulation and changes in Ca(2+) and Na(+) concentrations might have important roles in regulation of (14)C-acetate uptake in cultured rat astrocytes.

The regional distribution of PRMT8 transcript was examined in mouse brain using in situ hybridization (ISH) histochemistry. The PRMT8 cRNA probe was specifically hybridized with CNS and the signals were observed only in the neurons. The distribution of the neurons expressing PRMT8 mRNA was not even throughout the brain. All of the regions related to general somatosensory system expressed PRMT8 mRNA strongly. Most of the relay nuclei intervening the special somatosensory system, such as the auditory, visual, and vestibular systems, were packed with PRMT8 mRNA expressing neurons. Forebrain limbic areas and thalamic nuclei relevant to limbic areas were also strongly labeled with the probe. Some areas related to the motor system, such as the caudate putamen, Purkinje cells, inferior olivary nucleus and cerebellar nuclei expressed PRMT8 mRNA strongly. These findings suggest that PRMT8 is chiefly involved in the somatosensory and limbic systems, and a part of motor system.

Effects of prokineticins (PKs), a novel family of bioactive peptides with a mitogenic action to endothelial cells of the endocrine gland and testis, on astrocytic functions were examined. Mouse cultured astrocytes expressed PK-R1 type PK receptors, while there was little expression of the PK-R2 type. PKs caused increases in astrocytic cytosolic Ca2+ levels and BrdU incorporation. Increases in Ca2+ levels by PK-2 were diminished by U73122 (a phospholipase C inhibitor). PK-induced BrdU incorporation was inhibited by U73122, GF109203 (a protein kinase C inhibitor) and PD98059 (a MEK/ERK inhibitor). These results indicate that PK receptors are expressed in astrocytes and regulate astrocytic proliferation.

Micturition is controlled by a network of brainstem neurons involving the Barrington's nucleus. To depict clearly the brainstem system for micturition control, the present study was designed to record single neuronal activity in the mesopontine tegmentum including the Barrington's nucleus, and to observe its precise timing in relation to bladder contraction recorded simultaneously. About 1/5 of neurons encountered had firing modulated in relation to bladder contraction. Three types of neurons were distinguished; those which fired only prior to the start of contraction (type E1), those whose firing started shortly prior to and was maintained during contraction (type E2), and those whose firing was strongly suppressed during contraction (type I). Type E2 neurons were most frequently observed in the Barrington's nucleus and its close vicinity, while the neurons of the other two types were scattered widely in the mesopontine tegmentum. The results show clearly that direct neural signals to induce bladder contraction may arise from the Barrington's nucleus, and that the nucleus may receive regulatory inputs from wide areas of the mesopontine tegmentum. In addition, the present study clarified that the noradrenergic and cholinergic neurons, which are located in nuclei adjoining the Barrington's nucleus and function to control sleep/wakefulness, may not be concerned in controlling micturition directly.

The relation between unit activity in the laterodorsal tegmental (LDT) area and the state of the urinary bladder was examined in urethane-anesthetized rats. Neurons in the LDT area can be classified into two populations: broad-spike (possibly cholinergic) and brief-spike (non-cholinergic). When the rats showed cortical electroencephalographic activity with large amplitude lower frequency, indicative of deep anesthesia, more than 40% of the broad-spike neurons was excited and about 10% was inhibited by infusion of saline into the bladder. The response was followed by decrease in amplitude and slight increase in frequency of the cortical activity, i.e., lightening of anesthesia. During light anesthesia, excitation was observed only in less than 10% of the units, while 17% was inhibited. In the brief-spike neurons, a similar proportion (about 20%) was excited and less than 10% was inhibited by the distention during either state of anesthesia. About 10% of the broad-spike neurons in the LDT area and 30% of the brief-spike neurons examined were discharged prior to the bladder contraction. Such neurons of the brief-spike category were encountered frequently outside of the central gray; lateral, caudal and ventral to the main mass of cholinergic neurons in the LDT area. These results suggest the possible involvement of the broad-spike (cholinergic) neurons in the elevation of vigilance level caused by bladder distention. The brief-spike (non-cholinergic) neurons firing with relation to bladder contraction may be part of the micturition reflex center.

The density of specific prostaglandin E2 (PGE2) binding sites was quantitatively mapped in the rat brain using in vitro autoradiography. The anterior wall of the third ventricle and the nucleus solitary tract were found to have a very high density of binding sites (greater than 15 fmol/mg tissue). Two thalamic nuclei (paraventricular and anteroventral nuclei) and the dorsal parabrachial nucleus contained a high density of binding sites (10-15 fmol/mg tissue). Entorhinal cortex, ventral hippocampus, amygdala, dorsomedial hypothalamus, mammillary complex, some thalamic nuclei, central gray, superior colliculus, raphe nuclei, locus coeruleus, spinal trigeminal nucleus (caudal part) and the dorsal horn of the spinal cord (laminae 1 and 2) had each a moderate density of binding sites (5-10 fmol/mg tissue). Binding tended to occur in brain regions rich in neuronal cell bodies or neuronal cell processes (dendrites and axon terminals). PGE1, whose central actions are very similar to those of PGE2, had essentially the same pattern of binding sites as did PGE2 throughout the entire brain, suggesting there are receptors common to these two PGEs. In addition to already known functions of receptors common to these two PGEs. In addition to already known functions of PGE2 in the hypothalamus, which include fever genesis, promotion of wakefulness, cardiovascular control and LH-RH release, the unique distribution of extrahypothalamic PGE2 binding sites found in this study suggests its involvement in the processing or modulation of viscerosensory, somatosensory (nociceptive and possibly thermal) and visual inputs as well as in the central integration of autonomic and limbic functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Na+-independent L-[35S]cysteic acid (CA) accumulation in rat cortical synaptic membrane was examined. In the absence of Cl-, the accumulation was not observed. Addition of Cl- revealed the accumulation in a dose-dependent manner. Br- and NO3- also did. Ca2+-enhanced the Cl- -dependent accumulation, whereas low concentrations of Na+ reduced it. L-[35S]CA accumulation was inhibited by quisqualate, L-glutamate (L-Glu), L-cysteine sulfinate, D,L-homocysteic acid and D,L-2-amino-4-phosphonobutyrate (D,L-APB) potently. L-CA inhibited L-[3H]Glu accumulation in synaptic membrane in the presence of Cl-. The maximal inhibition of L-CA was equal to that of D,L-APB, but L-CA did not inhibit L-[3H]Glu accumulation in the absence of Cl-. These results show that L-[35S]CA selectively detects the Cl- -dependent L-Glu transporters in synaptic membrane.