1,721,065 research outputs found
Cellular mechanisms and second messengers: relevance to the psychopharmacology of bipolar disorders
Full text linkThe discovery of lithium's efficacy as a mood-stabilizing agent revolutionized the treatment of patients with bipolar disorder and after five decades, lithium continues to be the mainstay of treatment for bipolar disorder. Recent research on the molecular mechanism underlying the therapeutic effect of lithium has focused on how it changes the activities of cellular signal transduction systems, especially the cyclic AMP and phosphomositide second-messenger systems. Considerable data suggest that carbamazepine and valproate (VPA) are an alternative or adjunctive treatment to lithium. VPA, despite being dissimilar structurally to lithium, shares most of the effects of lithium at the level of protein kinase C (PKC). Like lithium, VPA reduces the activity of PKC and reduces the protein levels of different PKC isoforms, however the effects of VPA appear to be largely independent of inositol. The ton-term efficacy of VPA and lithium in bipolar disorder suggested that modulation of gene expression might be an important target for these drugs. Both VPA and lithium altered the expression of the early inducible genes for c-fos and cjun thus promoting the expression of specific proteins. The genes known to be regulated by the AP-1 family of transcription factors include genes for various neuropeptides, neurotrophins, receptors, transcription factors, enzymes, proteins that bind to cytoskeletal elements, and cytoprotective proteins such as bcl-2. In conclusion chronic treatment with lithium and other mood stabilizers, by regulating transcriptional factors, may modulate the expression of a variety of genes that compensate for aberrant signalling associated with the pathophysiology of bipolar disorder
Tumors in invertebrates
No full textTumors are ectopic masses of tissue formed by due to an abnormal cell proliferation. In this review tumors of several invertebrate species are examined. The description of tumors in invertebrates may be a difficult task, because the pathologists are usually inexperienced with invertebrate tissues, and the experts in invertebrate biology are not familiar with the description of tumors. As a consequence, the terminology used in defining the tumor type is related to that used in mammalian pathology, which can create misunderstandings in some occasions
Biologically active peptides in molluscs
No full textThe immune and neuroendocrine systems of invertebrates, as well as vertebrates, share a common
pool of molecules that have been conserved throughout evolution. Now we add a new interface to this
bidirectional interaction, demonstrating the involvement of the gut system, showing that these three
systems use the same biologically active peptides
Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus
No full textTo gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time PCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-γ mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine
P.2.a.012 Co-administration of fluoxetine with acetylsalicylic acid, but not flurbiprofen or celecoxib, for one week shows an antidepressant-like effect
No full textIncreasing evidence is now demonstrating the involvement of the immune system and in particular of their effectors, cytokines, in the development and progression of depression. In particular, it is worth underlying how pro-inflammatory cytokines appear to be increased in blood or brain of patients with major depression (MD) and that pharmacological use of pro-inflammatory cytokines (i.e. interferon alpha) may induce MD. These data suggest a role for inflammation in the pathogenesis of depression and that anti-inflammatory drugs may be used as an adjunctive therapy in the treatment of MD. However, some studies reported contradictory results and suggest that adverse effects may contraindicate the use of anti-inflammatory agents in the treatment of depression. Nevertheless, non-steroidal anti-inflammatory drugs (NSAIDs) can have different mechanisms of action also depending on the dose. This is true for the therapeutic effects as well as for the unwanted side effects.
On this basis, the present study aimed at evaluating the behavioural effect of the co-administration of fluoxetine (FLX, 5 mg/kg i.p.) with different NSAIDs in the chronic escape model of depression (CED). The CED model of depression possesses face, construct and pharmacological validity and is based on the induction, and maintenance, of an escape deficit upon exposing rats to unavoidable stressors. We previously demonstrated that, in this model, the stress-induced impaired behaviour can be resolved by one week of treatment with the co-administration of FLX (5 mg/kg/i.p.) plus acetylsalicylic acid (ASA, 45 mg/kg i.p.) but not FLX alone [1]. Here we evaluated the effect of the co-administration of FLX and flurbiprofen (FLB, an inhibitor of Cox-1 and Cox-2, 5 mg/kg, p.o.) or celecoxib (CLX, a selective COX2 inhibitor, 5 mg/kg, p.o.) in the CED model after 7 days of treatment. The co-administration FLX plus ASA (45mg/kg i.p.) was used as a positive control. Morever we tested the behavioral effect of different doses (45, 22.5 and 11.25 mg/Kg i.p.) of ASA as potentiating agent of the effect of fluoxetine.
Our study shows that only the co-administration of ASA with FLX reverted the stress-induced condition of escape deficit after 7 days of treatment. Moreover, the amplitude of the antidepressant-like effect was dose dependent. The percentage of the antidepressant response was about 90%, 60% and 40% for animals receiving FLX (5 mg/kg/i.p.) plus ASA at the dose of 45, 22.5 or 11.25 mg/Kg i.p. respectively. Both flurbiprofen and celecoxib, when administered together with FLX for 7 days, failed to induce an antidepressant-like effects in the CED model. Higher dose of FLB (50 mg/Kg p.o.) and CLX (20 mg/Kg p.o.) were also tested, but they were associated to high mortality rate (80% and 25% respectively).
These data demonstrated that neither all NSAIDs, nor all doses, may be useful in the treatment of depression while adverse effects can be potentiated or induced by the co-administration with antidepressants. Unraveling the cellular and molecular mechanisms behind the dissimilar behavioral response elicited by different anti-inflammatory drugs can contribute to understand the role of inflammation in the etiopathogensis of MD and to improve patient care.
[1] Brunello, N., Alboni, S., Capone, G., Benatti, C., Blom, J.M., Tascedda, F., Kriwin, P., Mendlewicz, J., 2006 Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol. 21:227-31
Acute and chronic changes in K+-induces depolarization alter NMDA and nNOS gene expression in cultured cerebellar granule cells.
No full textThe influence of low or high (10 or 25 mM) K+-induced membrane depolarization on the mRNA levels for NMDA receptor subunits
was investigated by RNase protection assay in cultured rat cerebellar granule cells. Cells, maintained for 7 days in K~5, a condition that
promotes their survival and maturation, express the highest levels of NR- 1 and NR-2A mRNA, whereas NR-2B is maximally expressed in
cells grown in K~- o. Acute changes in medium K ÷ concentration had a significant effect on the mRNA levels for NMDA receptor
subunits. A concomitant reduction of NR-2A mRNA and induction of NR-2B was observed following a 24-h shift of the culture medium
from K~- 5 to K~- o. Under these circumstances NR-2C, not detected in basal conditions, became expressed. Neuronal nitric oxide synthase,
an enzyme linked to NMDA receptor activation, was also influenced by growth conditions. Its expression, higher under low excitation
(K~-o), is induced in the shift from K~- 5 to K~- o and is markedly decreased in the opposite situation. These data indicate that several factors
may influence the expression of NMDA receptor subunits and consequently may modulate the function of this receptor complex and its
adaptation to acute and chronic changes in neuronal activity
Circulating phagocytes: The ancient and conserved interface between immune and neuroendocrine function
No full textImmune and neuroendocrine functions display significant overlap in highly divergent and evolutionarily distant models such as molluscs, crustaceans, insects and mammals. Fundamental players in this crosstalk are professional phagocytes: macrophages in vertebrates and immunocytes in invertebrates. Although they have different developmental origins, macrophages and immunocytes possess comparable functions and differentiate under the control of evolutionarily conserved transcription factors. Macrophages and immunocytes share their pools of receptors, signalling molecules and pathways with neural cells and the neuro-endocrine system. In crustaceans, adult transdifferentiation of circulating haemocytes into neural cells has been documented recently. In light of developmental, molecular and functional evidence, we propose that the immune-neuroendocrine role of circulating phagocytes pre-dates the split of protostomian and deuterostomian superphyla and has been conserved during the evolution of the main groups of metazoans
Psicofarmacologia clinica
No full textIl volume raccoglie le acquisizioni più recenti sull'utilizzo clinico delle principali classi di psicofarmaci impiegati nella terapia delle patologie psichiatriche di più rilevante intersse sociale. Si divide in due sezioni principali: le classi di farmaci psichiatrici e i trattamenti psicofarmacologici. Nella Sezione I, per ogni molecola all'interno di una specifica classe, sono commentati i dati di studi preclinici e in fase clinica; inoltre, sono illustrati gli aspetti farmacodinamici e farmacocinetici, le indicazioni terapeutiche, i dosaggi, gli effetti collaterali e le interazioni con altri farmaci, psichiatrici e non psichiatrici. La Sezione II presenta lo stato dell'arte della terapia farmacologica nelle principali malattie psichiatriche. Gli autori descrivono, inoltre, la farmacoterapia in speciali popolazioni, come i bambini e gli adolescenti, i pazienti affetti da malattie sistemiche e gli anziani. Alcuni capitoli son infine dedicati alla psicofarmacoterapia in situazioni particolari, quali la gravidanza, l'allattamento e le emergenze. Particolare cura è stata posta nelladattare la descrizione delle singole molecole alla realtà italiana: sono stati inseriti alcini farmaci non in commercio negli Stati Uniti ma venduti in Italia; inoltre, laddove la legislazione del nostro Paese differisce da quella americana, si è provveduto a fornire indicazioni di sicuro riferimento per lo specialista italiano. Questo volume è una preziosa fonte di informazioni per psichatri, psicofarmacologi, neurologi, geriatri e specializzandi, nonché un valido strumento di approfondimento per gli studenti delle Facoltà di Medicina e Farmacia
Recommended from our members
The nexus of social alliances and diverse moral domains: a bedrock for participatory clinical research
Full text linkTranscriptional effect of serotonin in the ganglia of Lymnaea stagnalis
Full text linkThe serotonin system (5HT) is highly conserved in both vertebrates and invertebrates, and numerous evidence supports a biological link between 5HT and numerous animal function. In the present paper we evaluated the transcriptional effects of a serotonergic stimulation on selected targets involved in 5HT signalling and neurotransmission in the central nervous system of the great pond snail Lymnaea stagnalis. Adult snails were treated acutely (6 h) or chronically (48 h) with either 5-hydroxytrypthophan (5-HTP 1mM), the immediate precursor of serotonin, fluoxetine (FLX 1Î1⁄4M), a selective serotonin reuptake inhibitor, or a combination of two. The central ring ganglia were dissected and used for q-PCR gene expression analysis. Transcription was strongly induced following a chronic, but not an acute, exposure to 5-HTP in the ganglia of Lymnaea. In particular, LymCREB1 and LymP2X mRNA levels were decreased following a 6 h exposure and increased in snails receiving 5-hydroxytryptophan for 48 h. Interestingly, this effect was reduced when snails were exposed chronically to both 5-HTP and FLX, suggesting a role for SERT in mediating the effect of 5-hydroxytryptophan. These data suggest that L. stagnalis is suited to unravel the complexity of the serotonin signaling pathway
- …
