Calcium-binding proteins in the retina of a calbindin-null mutant mouse.

Calcium-binding proteins are abundantly expressed in many neurons of mammalian retinae. Their physiological roles are, however, largely unknown. This is particularly true for calcium-modulating proteins ("calcium buffers") such as calbindin D28k.

The "questions to ask about your medicines" campaign. An evaluation of pharmacists' and the public's response.

Objectives: The purpose of this study was to assess the impact of the WHO/EuroPharm Forum "Questions to Ask About Your Medicines" campaign on patient counseling in Finnish community pharmacies.

Methods: The impact of the campaign was assessed by comparing the baseline findings with those at 3 months and 12 months after the implementation. The research methods involved observation of pharmacist-customer interactions, followed by personal interview of the customer.

Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha.

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for central dopaminergic neurons, motor neurons and several other populations of neurons in the central and peripheral nervous system. GDNF and its receptor complex of c-RET tyrosine kinase and a glycosyl-phosphatidylinositol linked protein GDNFR-alpha are of great interest due to their potential use in the therapy of Parkinson's and motoneuron diseases. We have cloned the human and rat cDNA sequences of GDNFR-beta, a new gene encoding for a 464 amino acid long homologue of GDNFR-alpha, and assign the locus of this new gene to human chromosome 8p21-22 and mouse chromosome 14D3-E1.

Purkinje cell survival and axonal regeneration are age dependent: an in vitro study.

Purkinje cells are among the most resistant neurons to axotomy and the most refractory to axonal regeneration. By using organotypic cultures, we have studied age- and environment-related factors implicated in Purkinje cell survival and axonal regeneration. Most Purkinje cells taken from 1- to 5-d-old rats, the period in which these neurons are engaged in intense synaptogenesis and dendritic remodeling, die 1 week after plating, whereas if cultured before or after this period, Purkinje cells survive, even in the absence of deep nuclear neurons, their postsynaptic targets.

Binding of pinoline on the 5-hydroxytryptamine transporter: competitive interaction with [3H] citalopram.

Pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) is a naturally occurring compound in the mammalian body which inhibits 5-hydroxytryptamine (5-HT) uptake and exerts antidepressant-like behavioural effects in rats. The present study investigates the effects of pinoline on [3H]citalopram binding to the 5-HT transporter on rat brain. Our experiments revealed that pinoline inhibits [3H]citalopram binding with IC50 1255 +/- 167 nM and Ki 572 +/- 76 nM; Hill coefficient for inhibition was close to 1.

Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene.

Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear.

Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice.

Calbindin-D28k (calbindin) is an intracellular calcium binding protein of unknown in vivo function. It is abundantly expressed in many populations of neurons, and it can, presumably by buffering calcium overload, protect cells against excitotoxic damage. In the midbrain, calbindin is preferentially expressed in those dopamine neurons which are spared from degeneration in Parkinson's disease and its animal models.

Most classes of dorsal root ganglion neurons are severely depleted but not absent in mice lacking neurotrophin-3.

During development, many neurons in the dorsal root ganglia require neurotrophin-3 for survival. However, it is not known precisely which subpopulations of sensory neurons, other than the proprioceptive afferents, are neurotrophin-3 dependent in vivo. In this study, using a battery of neurochemical markers that label different subpopulations of dorsal root ganglion neurons, we found a widespread, about 60-65% loss of cells in most subpopulations in neurotrophin-3 deficient mice.

Autoradiographic localization of [3H]-pinoline binding sites in mouse tissues.

Pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) has been found in similar concentrations to those of melatonin in various mammalian tissues. The present study investigates the subcellular distribution of in vivo administered [3H]-pinoline in mouse tissues using light and electron microscopic autoradiography. The antioxidative capacity of pinoline was determined in vitro and compared with that of the structurally similar pineal hormone melatonin.

Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development.

Bcl-2 is a major regulator of programmed cell death, a critical process in shaping the developing nervous system. To assess whether Bcl-2 is involved in regulating neuronal survival and in mediating the neuroprotective action of neurotrophic factors, we generated Bcl-2-deficient mice. At birth, the number of facial motoneurons, sensory, and sympathetic neurons was not significantly changed, and axotomy-induced degeneration of facial motoneurons could still be prevented by brain-derived neurotrophic factor (BDNF) or ciliary neurotrophic factor (CNTF).

Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation.

Neurotrophin-3 (NT-3) is required for the development of most sensory neurons of the dorsal root ganglia. Using electrophysiological techniques in mice with null mutations of the NT-3 gene, we show that two functionally specific subsets of cutaneous afferents differentially require this factor: D-hair receptors and slowly adapting mechanoreceptors; other cutaneous receptors were unaffected. Merkel cells, which are the end organs of slowly adapting mechanoreceptors, are virtually absent in 14-day-old homozygous mutants and are severely reduced in adult NT-3 heterozygous animals.

Histaminergic modulation of neocortical spindling and slow-wave activity in freely behaving rats.

Histaminergic H3 receptor antagonists stimulate neuronal histamine release and could consequently have a number of physiological effects in the brain. The effects of H3 receptor blockade, induced by systemically administered thioperamide, were assessed on the frontal cortex electroencephalographic (EEG) properties in freely behaving rats. The relationship of EEG activity variables to endogenous brain histaminergic markers was also examined, both in controls and in portocaval anastomosis (PCA)-operated rats (which show increased levels of brain histamine and t-methylhistamine).

Formation of tetrahydroharman (1-methyl-1,2,3,4-tetrahydro-beta-carboline) by Helicobacter pylori in the presence of ethanol and tryptamine.

Helicobacter pylori contains alcohol dehydrogenase which oxidizes ethanol to acetaldehyde. In the present study, H. pylori cytosol was incubated in a buffered media at pH 6.

Changes in GABA-benzodiazepine receptor complex and in peripheral benzodiazepine receptors in male mice after copulation.

We studied the effect of copulation on GABA and benzodiazepine (BZD) receptors in the male mouse. After copulation, there was an 18% increase in the in vitro number of [3H]muscimol binding sites in frontal cortex. No changes were observed in central BZD binding sites labelled either in vivo by [3H]flunitrazepam or in vitro (in olfactory bulbs and in frontal cortex) by [3H]flumazenil, but further in vitro studies demonstrated that the GABA-stimulated [3H]flunitrazepam binding was reduced in both frontal cortex and olfactory bulbs.

Differential regulation of cyclic GMP levels in the frontal cortex and the cerebellum of anesthetized rats by nitric oxide: an in vivo microdialysis study.

A microdialysis method combined with a sensitive radioimmunoassay was used to monitor extracellular cyclic GMP (cGMP) levels in the frontal cortex and the cerebellum of anesthetized rats in vivo. Basal cGMP release remained constant throughout the perfusion period and was approximately 2 fmol/30 min in the frontal cortex and approximately 4 fmol/30 min in the cerebellum. The nitric oxide (NO) donor sodium nitroprusside (SNP) stimulated cGMP release transiently in both regions.

Platelet serotonin uptake sites increased in drinkers of ayahuasca.

The binding of [3H]citalopram to the platelet 5-hydroxytryptamine (5-HT) transporter was measured in a group of healthy male drinkers of ayahuasca, a psychoactive sacrament indigenous to Amazonia, and a group healthy male controls. An increased number of binding sites (Bmax) in the platelets of ayahuasca drinkers was found, while the dissociation constant (Kd) remained the same for both groups. If indicative of neuronal 5-HT uptake activity, these results would suggest a decreased concentration of extracellular 5-HT, or a response to increased production and release of 5-HT.

Inhibition of brain histamine synthesis increases food intake and attenuates vasopressin response to salt loading in rats.

Alpha-fluoromethylhistidine (FMH), a histamine synthesis inhibitor, was infused into the lateral cerebral ventricle of male Long-Evans rats for 7 days at a dose of 60 mcg/day. During this period animals were housed in metabolic cages; water and food consumption were measured and urine samples were collected. FMH-treated rats ate significantly more than controls and had a significantly greater weight increase.

Influence of flumazenil on the learning-enhancing effect of ambocarb in rats.

The effects of flumazenil (Ro 15-1788) and a new beta-carboline, ambocarb (AMB), on learning were investigated using the multichoice maze. The drugs, administered either alone or simultaneously, were injected once a day before training for eight days. AMB, administered alone, improved the performance and decreased the working errors, whilst flumazenil had no effect on performance during its sole administration but weakly prevented the learning-improving effect of AMB.

Neurotransmitters in the nervous system of Macoma balthica (Bivalvia).

The distribution of histamine-, octopamine-, gamma-aminobutyric acid- (GABA) and taurine-like immunoreactivity in the bivalve mollusc Macoma balthica was studied immunocytochemically with antisera produced in rabbits. Histamine levels in the ganglia and whole animals were also measured by high-performance liquid chromatography using a postcolumn derivatization method. Immunoreactivity for these substances, except for taurine, is found in the central nervous system of this species.

Ethanol and delta-sleep-inducing peptide: effects on brain monoamines.

The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats.

The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat.

Rats were twice daily (2 x 10 mg/kg, i.p.) treated for three weeks with the peripheral benzodiazepine (BZ) receptor ligands Ro 5-4864 (4'-chlorodiazepam) and PK 11,195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox ami de).

Multiple neurotransmitters in the tuberomammillary nucleus: comparison of rat, mouse, and guinea pig.

Tuberomammillary neurons in the posterior hypothalamus are the sole source of neuronal histamine in adult mammalian brain. In the rat, these cells are reported to contain immunoreactivity for gamma-aminobutyric acid (GABA) and several neuropeptides. We compared the presence of these substances in the tuberomammillary cells of the rat, mouse, and guinea pig.

Effects of smoking abstinence and chain-smoking on puffing topography and diurnal nicotine exposure.

Effects of chain-smoking, a 15-h smoking abstinence, and the nicotine yield of cigarettes on puff indices were studied in eight healthy smokers by using a controlled crossover study design. Puff parameters were measured puff by puff with a portable measuring device when 10 or 20 cigarettes, with nicotine yields of 0.3 and 1.

Fast cyclic voltammetry of oxidizable species; depth profile in the rat striatum with and without potassium stimulation of the median forebrain bundle.

Fast cyclic voltammetry was used to monitor the release of dopamine in the caudate nucleus following potassium stimulation of the median forebrain bundle and to determine the characteristics of the small basal oxidation current while dipping of an electrode with a large tip (0.3 mm) in the caudate nucleus. The oxidation current was shown to be greater just after the electrode reached the caudate area than at a time 15-20 s after its arrival.