Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

Background  

During the preovulatory surge of gonadotropin-releasing hormone (GnRH), a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia.     

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

Background  

In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition.     

Detrimental effects of tropisetron on permanent ischemic stroke in the rat

Background  

Recent in vitro evidence indicates that blockade of 5-hydroxytryptamine (5-HT) receptor 3 (5-HT₃) is able to confer protection in different models of neuronal injury. The purpose of the present study was to investigate the effect of tropisetron, a 5-HT₃ receptor antagonist, on infarct size and neurological score in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in the rat.     

Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson's disease

Background  

Predominantly, magnetic resonance imaging (MRI) studies in animal models of Parkinson's disease (PD) have focused on alterations in T₂ water ¹H relaxation or ¹H MR spectroscopy (MRS), whilst potential morphological changes and their relationship to histological or behavioural outcomes have not been appropriately addressed. Therefore, in this study we have utilised MRI to scan in vivo brains from rodents bearing a nigrostriatal lesion induced by intranigral injection of the proteasome inhibitor lactacystin.     

<Emphasis Type="Italic">N</Emphasis>-arachidonoyl glycine,an abundant endogenous lipid,potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor

Background  

Microglia provide continuous immune surveillance of the CNS and upon activation rapidly change phenotype to express receptors that respond to chemoattractants during CNS damage or infection. These activated microglia undergo directed migration towards affected tissue. Importantly, the molecular species of chemoattractant encountered determines if microglia respond with pro- or anti-inflammatory behaviour, yet the signaling molecules that trigger migration remain poorly understood. The endogenous cannabinoid system regulates microglial migration via CB₂ receptors and an as yet unidentified GPCR termed the 'abnormal cannabidiol' (Abn-CBD) receptor. Abn-CBD is a synthetic isomer of the phytocannabinoid cannabidiol (CBD) and is inactive at CB₁ or CB₂ receptors, but functions as a selective agonist at this G_i/o-coupled GPCR. N-arachidonoyl glycine (NAGly) is an endogenous metabolite of the endocannabinoid anandamide and acts as an efficacious agonist at GPR18. Here, we investigate the relationship between NAGly, Abn-CBD, the unidentified 'Abn-CBD' receptor, GPR18, and BV-2 microglial migration.     

Human neuronal stargazin-like proteins, γ2, γ3 and γ4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.

Background  

Stargazin (γ₂) and the closely related γ₃, and γ₄ transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC) γ subunits and transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA) receptor regulatory proteins (TARPs). In this investigation, we examined the distribution patterns of the stargazin-like proteins γ₂, γ₃, and γ₄ in the human central nervous system (CNS). In addition, we investigated whether human γ₂ or γ₄ could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes.     

Transient change in GABAA receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration

Background  

Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABA_A receptor subunit gene expression during PC degeneration.     

The excitation cascade of <Emphasis Type="Italic">Limulus</Emphasis> ventral photoreceptors: guanylate cyclase as the link between InsP<Subscript>3</Subscript>-mediated Ca<Superscript>2+</Superscript>release and the opening of cGMP-gated channels

Background  

Early stages in the excitation cascade of Limulus photoreceptors are mediated by activation of G_q by rhodopsin, generation of inositol-1,4,5-trisphosphate by phospholipase-C and the release of Ca²⁺. At the end of the cascade, cGMP-gated channels open and generate the depolarizing receptor potential. A major unresolved issue is the intermediate process by which Ca²⁺ elevation leads to channel opening.     

Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons

Background  

Accumulated evidence suggests that hydrogen peroxide (H₂O₂) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H₂O₂ in neuronal insulin receptor activation and the origin of insulin-induced H₂O₂ in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H₂O₂ is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H₂O₂ production, thus playing an integral role in insulin receptor autophosphorylation in neurons.     

Regulation of prokineticin 2 expression by light and the circadian clock

Background  

The suprachiasmatic nucleus (SCN) contains the master circadian clock that regulates daily rhythms of many physiological and behavioural processes in mammals. Previously we have shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCN output molecule responsible for circadian locomotor rhythms. As light is the principal zeitgeber that entrains the circadian oscillator, and PK2 expression is responsive to nocturnal light pulses, we further investigated the effects of light on the molecular rhythm of PK2 in the SCN. In particular, we examined how PK2 responds to shifts of light/dark cycles and changes in photoperiod. We also investigated which photoreceptors are responsible for the light-induced PK2 expression in the SCN. To determine whether light requires an intact functional circadian pacemaker to regulate PK2, we examined PK2 expression in cryptochrome1,2-deficient (Cry1-/-Cry2-/-) mice that lack functional circadian clock under normal light/dark cycles and constant darkness.     

<Emphasis Type="Italic">N</Emphasis>-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus <Emphasis Type="Italic">Branchiostoma lanceolatum</Emphasis>

Background  

NMDA (N-methyl-D-aspartic acid) is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland.     

Pilot Study: Understanding the Effects of Voicing Intervention on HFCC Therapy in People with Cystic Fibrosis

The efficacy of High-Frequency Chest Compression (HFCC) airway clearance therapy is linked to the induced-peak expiratory airflow pulse (IPEF) at the patient's mouth. The authors' goal was to determine the conditions that yield the highest IPEF using HFCC running at 6 Hz in conjunction with voicing intervention. A pilot experimental study was conducted in a laboratory setting. Six adults with moderate to mild cystic fibrosis (CF) and 10 healthy adults participated. When the component characteristics of voicing were disregarded in data analysis of four conditions, voicing only intervention (V₁I₀), HFCC only intervention (V₀I₁), voicing intervention and HFCC intervention combinations (V₁I₁) and nonintervention (V₀I₀), V₀I₁ had significantly higher (P < 0.0001) IPEF. Data analyses of 64 separate voicing component characteristics, frequency (×4), amplitude (×4), and rhythm (×2) of voicing intervention, in addition to absence and presence of HFCC intervention (V₁I₀ and V₁I₁), were examined. One condition in V₁I₀ had significantly higher (P < 0.000001) IPEF than other conditions in V₁I₀ and V₁I₁ in both experimental and control groups. Based on these findings, V₁I₁ may yield higher IPEF than V₀I₁. One condition of amplitude component of voicing and one condition of rhythm component of voicing had significantly higher (P < 0.0001) IPEF than other conditions of amplitude and rhythm components in both CF and control subjects. Analysis of this combined condition of V₁I₁ showed that this specific condition of V₁I₁ had significantly higher (P < 0.000001) IPEF than any other conditions in V₁I₁ and V₀I₁.     

Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

Background

Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.

Results

Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ET_B, 5-HT_1B and AT₁ receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score.

Conclusion

These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy.     

Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, <Emphasis Type="Italic">Ictalurus puntatus</Emphasis>

Background  

The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg). Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR). Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I) and Phaseolus vulgaris Erythroagglutinin (PHA-E), inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance of barbel membranes reconstituted into lipid bilayers.     

Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

Background

G protein-coupled receptors (GPCRs) interact with heterotrimeric GTP-binding proteins (G proteins) to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP) kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways.

Results

Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT_2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK) inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1) on the 5-HT_2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT_2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT_2C receptor abolished the effect of insulin.

Conclusion

These results show that insulin signaling can inhibit 5-HT_2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.     

Evidence for non-independent gating of P2X<Subscript>2</Subscript> receptors expressed in <Emphasis Type="Italic">Xenopus</Emphasis>oocytes

Background  

P2X₂ receptor is an ATP-activated ion channel which is widely expressed in the nervous system, and mediates synaptic transmission.     

Synthesis of thiolate-protected silver nanocrystal superlattices from an organometallic precursor and formation of molecular di-<Emphasis Type="Italic">n</Emphasis>-alkyldisulfide lamellar phases

Abstract  

Silver nanocrystal superlattices (NCSs) stabilized by hexadecanethiol have been prepared through reduction of [Ag(hexadecanethiolate)] _n , formed in situ by reaction of the organometallic precursor [Ag(C₆F₅)] and hexadecanethiol. The nanostructures have been characterized by transmission electron microscopy (TEM) and X-ray diffractometry (XRD). Several reaction parameters such as solvent (anisole or toluene), reaction temperature (150 or 120 °C) or silver:thiol ratio (1:1 or 2:1) have been studied. The NCSs are formed by silver nanoparticles which sizes range from 3.7 to 5.1 nm, depending on the reaction conditions. The formation a of lamellar phase of di-n-hexadecyldisulfide by oxidation of the hexadecanethiolate ligands bonded to Ag(I) is detected by XRD.     

Plasticity of histamine H<Subscript>3</Subscript>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat

Background  

In rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recovery (e.g., diminished symptoms), encompassing 1 week after unilateral labyrinthectomy, has been termed vestibular compensation. Evidence suggesting that the histamine H₃ receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H₁ receptor agonist and an H₃ receptor antagonist, can accelerate the process of vestibular compensation.     

Expression of iron-related genes in human brain and brain tumors

Background  

Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP), HFE, neogenin (NEO1), transferrin receptor 1 (TFRC), transferrin receptor 2 (TFR2), and hemojuvelin (HFE2) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.