Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Bruno, Valeria  (90)
Type of Medium
Language
Year
  • 1
    Language: English
    In: Current Opinion in Pharmacology, 2015, Vol.20, p.89(6)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.coph.2014.12.002 Byline: Ferdinando Nicoletti, Valeria Bruno, Richard Teke Ngomba, Roberto Gradini, Giuseppe Battaglia Abstract: * There is still hope for a clinical use of mGlu ligands. * Targeted disorders may still include schizophrenia and Parkinson's disease. * Other disorders, such as SCA1 and absence epilepsy might be treated with mGlu drugs. Author Affiliation: (1) Department of Physiology and Pharmacology, University Sapienza, Piazzale Aldo Moro, 5, 00185 Roma, Italy (2) I.R.C.C.S Neuromed, Localita Camerelle, 86077 Pozzilli, Italy (3) Department of Experimental Medicine, University 'Sapienza', Viale Regina Elena, 324, 00161 Roma, Italy
    Keywords: Glutamate
    ISSN: 1471-4892
    Source: Cengage Learning, Inc.
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: PLoS ONE, 2012, Vol.7(9)
    Description: We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH + ) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl- p -tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH + neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH + neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH + neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH + neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH + neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH + neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH + neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH + neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH + neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH + neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.
    Keywords: Research Article ; Biology
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Neurological Sciences, 2011, Vol.31(Supplement 3), pp.283-288
    Description: Monoclonal antibodies, first introduced in cancer therapy and to prevent allograft rejection, represent new pharmacological tools for the treatment of autoimmune diseases. With the knowledge of immunological movements in autoimmunity, it is now possible to target each single step of the immune process, from the activation of T lymphocytes in lymph nodes to the formation of the immunological synapse, and to T cell differentiation and cytokine production. However, this approach is still not devoid of adverse effects. In fact, even if monoclonal antibodies exert selective immunomodulation by targeting only cells expressing a specific antigen, a widespread perturbation of the immune system is induced, leading to a predisposition for infections and infestations and to the occurrence of tumours.
    Keywords: Biological drugs ; Monoclonal antibodies ; Autoimmune diseases ; Multiple sclerosis
    ISSN: 1590-1874
    E-ISSN: 1590-3478
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: 2012, Vol.7(9), p.e44025
    Description: We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH + ) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl- p -tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH + neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH + neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH + neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH + neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH + neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH + neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH + neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH + neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH + neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH + neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.
    Keywords: Research Article ; Biology ; Neuroscience ; Developmental Biology
    E-ISSN: 1932-6203
    Source: PLoS
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Endocrinology, December 2012, Vol.153(12), pp.5940-8
    Description: Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.
    Keywords: Cell Death -- Drug Effects ; Estradiol -- Metabolism ; N-Methylaspartate -- Pharmacology ; Neurons -- Metabolism ; Receptors, Metabotropic Glutamate -- Metabolism
    ISSN: 00137227
    E-ISSN: 1945-7170
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Nature Medicine, 2010, Vol.16(8), p.897
    Description: High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper ([T.sub.H]17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling--which would normally decrease intracellular cAMP formation--biased [T.sub.H] cell commitment to the [T.sub.H]17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T ([T.sub.reg]) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis.
    Keywords: Multiple Sclerosis -- Risk Factors ; Multiple Sclerosis -- Care And Treatment ; Multiple Sclerosis -- Research ; Neurotransmitter Receptors -- Physiological Aspects ; Neurotransmitter Receptors -- Research ; T Cells -- Physiological Aspects ; T Cells -- Research;
    ISSN: 1078-8956
    E-ISSN: 1546170X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Neuroscience, 05 November 2017, Vol.363, pp.142-149
    Description: Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3 g/kg), which caused the death of 〉70% of Brn-3a RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5 mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration.
    Keywords: Retinal Ganglion Cells ; Mglu1 Receptors ; Monosodium Glutamate ; Jnj16258695 ; Crv4 Mice ; Anatomy & Physiology
    ISSN: 0306-4522
    E-ISSN: 1873-7544
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Neuroscience Letters, 2010, Vol.478(3), pp.128-130
    Description: The -amino acid, -aspartate, is abundant in the developing brain, yet its function is unknown. Addition of -aspartate to hippocampal or cortical slices prepared from 8- to 9-day-old rats stimulated polyphosphoinositide (PI) hydrolysis to a slightly greater extent than -glutamate. The action of -aspartate was concentration-dependent with an apparent EC value of 1 mM and a maximal stimulation of 6- and 20-fold in cortical and hippocampal slices, respectively. Stimulation of PI hydrolysis by -aspartate was largely reduced by pharmacological blockade of mGlu5 metabotropic glutamate receptors with 2-methyl-6-(phenylethynyl)pyridine. These findings suggest that -aspartate behaves as an endogenous agonist of mGlu5 receptors during early postnatal life.
    Keywords: D-Aspartate ; Metabotropic Glutamate Receptors ; Polyphosphoinositide Hydrolysis ; Hippocampal Slices ; Cortical Slices ; Medicine ; Anatomy & Physiology
    ISSN: 0304-3940
    E-ISSN: 1872-7972
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: PLoS ONE, 01 January 2011, Vol.6(1), p.e16447
    Description: The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1), an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central nervous system. Drugs that rescue the canonical Wnt pathway may attenuate hippocampal damage in major depression and other stress-related disorders.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Epilepsia, November 2017, Vol.58(11), pp.1993-2001
    Description: Summary Objectives Thrombospondins, which are known to interact with the [alpha]2[delta] subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). Methods We measured the transcripts of thrombospondin-1 and [alpha]2[delta] subunit, and protein levels of [alpha]2[delta], Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Results Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. Significance These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs.
    Keywords: Thrombospondins ; Absence Epilepsy ; Α 2 Δ Subunit ; Wag /Rij Rats ; Genetic Variants
    ISSN: 0013-9580
    E-ISSN: 1528-1167
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages