Stress and cocaine interact to modulate Arc/Arg3.1 expression in rat brain.

Rationale: The interaction between stress and drugs of abuse is a critical component of drug addiction, but the underlying molecular mechanisms remain elusive. Arc/Arg3.1 is an effector immediate early gene that may represent a bridge connecting short- and long-term neuronal modifications associated with exposure to stress and drugs of abuse.

Characterization of the electrocardiographic pattern of individuals with cerebral palsy.

Background: Dentists of Lar São Francisco observed during dental treatment that children with cerebral palsy (CP) had increased heart rate (HR) and lower production of saliva. Despite the high prevalence of CP found in the literature (2.08-3.

Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress.

It is known that long-term treatment with antipsychotic drugs (APDs) produces neuroadaptive changes through the modulation of different proteins that, by enhancing neuronal plasticity and cellular resiliency, may improve core disease symptoms. The aim of this study was to investigate the ability of chronic treatment with the novel antipsychotic lurasidone to modulate BDNF expression in hippocampus and prefrontal cortex, under basal conditions or in response to an acute stress, a major precipitating element in psychiatric disorders. By means of real-time PCR, we found that (1) chronic lurasidone treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus; (2) the modulation of BDNF mRNA levels in response to acute swim stress in lurasidone-treated rats was markedly potentiated in hippocampus, and to less extent in prefrontal cortex, through the selective regulation of different neurotrophin isoforms.

ELAV-GAP43 pathway activation following combined exposure to cocaine and stress.

Rationale: An increasing body of evidence suggests that drug addiction engages circuits also associated with memory processes. In particular, in the hippocampus, a substantial similarity seems to exist between the changes yielded by drugs of abuse and those induced by hippocampal-dependent learning.

Objectives: Considering the key involvement of neuronal Embryonic Lethal Abnormal Vision (nELAV) proteins in memory processes occurring within the hippocampus and the critical role of stress for compulsive drug use and relapse, we investigated the effect of cocaine and stress challenges on the activation of the nELAV cascade.

GAPP Italy: "A survey on asthma on Italian physicians and patients".

Guidelines recognize the importance of achieving and maintaining asthma control: the treatment strategies nw available allow the control of the great majority of patients with asthma but despite many efforts only 5% of patients achieve guideline-defined asthma control. The GAPP (The Global Asthma Physician and Patient survey) is a global quantitative survey with the aiim of identifying barriers to optimal management of asthma. Physicians and adult patients with persistent asthma have been interviewed with closed-ended questions questionnaire.

Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats: comparison with methylphenidate.

The stimulant methylphenidate and the non-stimulant atomoxetine are widely used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but the molecular mechanisms of their therapeutic action are not fully understood. The aim of our study was to investigate, in adolescent rats, the sub-chronic effect of these two drugs on neuronal plasticity, through a detailed analysis of BDNF expression and signalling in order to establish the contribution of these mechanisms in the pharmacotherapy of ADHD. Atomoxetine (ATX) up-regulated BDNF mRNA levels in the hippocampus whereas methylphenidate (MPH) increased BDNF gene expression in the nucleus accumbens and caudate-putamen.

AMPA GluR-A receptor subunit mediates hippocampal responsiveness in mice exposed to stress.

Because stress represents a major precipitating event for psychiatric disorders, it is important to identify molecular mechanisms that may be altered in vulnerable individuals when exposed to stress. Here, we studied GluR-A(-/-) mice, animals with compromised AMPA receptor signaling, and characterized by a schizophrenic as well as depressive phenotype to investigate changes occurring in response to an acute stress. Wild-type and GluR-A(-/-) mice were exposed to a single immobilization stress and sacrificed immediately after the end of the stress for the analysis of activity regulated genes and of glutamatergic synapse responsiveness.

Repeated electroconvulsive shock (ECS) alters the phosphorylation of glutamate receptor subunits in the rat hippocampus.

Glutamate and its receptors are involved in the pathophysiology of mood disorders and have recently emerged as potential targets for the pharmacotherapy of depression. In rats, we investigated plasticity changes of the glutamatergic system evoked by electroconvulsive shock (ECS), which represents the most effective therapy for patients who are refractory to antidepressants. Chronic ECS produced a marked increase in the phosphorylation of the regulatory NMDA receptor subunit NR2B (Ser1303) and the AMPA receptor subunit GluR-A (Ser831) in the hippocampus, with no effects on the obligatory subunit NR1.

Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors.

Spinal cord injury (SCI) triggers a complex ischemic and inflammatory reaction, involving activation of neurotransmitter systems, in particular glutamate, culminating in cell death. We hypothesized that SCI might lead to alteration in the RNA editing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors that govern critical determinants of neuronal survival. To this end, we examined the molecular changes set in motion by SCI that affect the channel properties of AMPA receptors.

GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone.

Recent evidence showed that neurotransmitters are synthesised in glial cells, such as the Schwann cells, which form myelin sheaths in the PNS. While the presence of GABA type A (GABA-A) receptors has been previously demonstrated in these cells, the evidence of GABA synthesis remained still elusive. In an attempt to demonstrate the presence of GABA in rat Schwann cells, we adopted a strategy, using several integrated neurochemical, molecular as well as immunocytochemical approaches.

Cognitive effects of second-generation antipsychotics: current insights into neurochemical mechanisms.

Historically, pharmacotherapy for schizophrenia was mainly focused on finding drugs to treat psychotic symptoms only, without addressing other crucial domains of the disorder such as cognitive impairments. As a result, these domains have remained undertreated. In this review, we discuss recent preclinical research efforts, including investigation of synaptic mechanisms as well as intracellular signalling pathways and mechanisms involved in neuroplasticity and cell resilience, that may represent new mechanisms participating in the pathogenesis of schizophrenia, particularly at the level of the prefrontal cortex and hippocampus, and that might lead to the development of drugs that can counteract, at least partially, the cognitive impairments typical of schizophrenia.

Antipsychotic drug actions on gene modulation and signaling mechanisms.

Schizophrenia is a debilitating chronic mental disorder characterized by significant lifetime risk and high social costs. Although its etiology remains unknown, many of its symptoms may be mitigated by treatment with antipsychotic drugs (APDs). These compounds, generally classified as first- or second-generation antipsychotics, have complex receptor profiles that may account for short-term clinical response and normalization of acute manifestation of the disease.

Prenatal stress alters glutamatergic system responsiveness in adult rat prefrontal cortex.

Exposure to stress during gestation alters brain development resulting in permanent alterations that may increase susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript we examined the effects of prenatal stress on critical determinants of the glutamatergic synapse under basal conditions as well as in response to acute stress. The main finding of this work is that gestational stress altered the responsiveness of the glutamatergic system following a challenge at adulthood.

Acute spinal cord injury reduces brain derived neurotrohic factor expression in rat hippocampus.

Spinal cord injury (SCI) is a devastating event which causes dramatic changes in the everyday life of the patient. We have found that acute SCI reduced BDNF expression selectively in the hippocampus of lesioned rats, a decrease which persists at least 1 week, thus identifying the modulation of the neurotrophin biosynthesis as an important mechanism underlying brain vulnerability to SCI. These data are the first to show that SCI alters hippocampal BDNF expression and identify the neurotrophin as a potential target through which SCI changes brain functions, a notion that might prove useful in understanding the mechanisms underlying brain vulnerability to SCI.

S.TR.E.A.M., system for trace element assessment with mosses. An equation to estimate mercury concentration in freshwaters.

Hundred experiments of Hg bioaccumulation with the aquatic moss Rhynchostegium riparioides (Hedw.) C.E.

Repeated stress prevents cocaine-induced activation of BDNF signaling in rat prefrontal cortex.

In this report we provide evidence that repeated stress prevents cocaine-induced activation of BDNF expression and signaling in rat prefrontal cortex. A single injection of cocaine up-regulates BDNF expression in sham (i.e.

Unrelated developmental neurotoxicants elicit similar transcriptional profiles for effects on neurotrophic factors and their receptors in an in vitro model.

Diverse developmental neurotoxicants can often produce similar functional and behavioral outcomes. We examined an organophosphate pesticide (diazinon), an organochlorine pesticide (dieldrin) and a metal (Ni(2+)) for effects on the expression of neurotrophic factors and their receptors and modulators in differentiating PC12 cells, an in vitro model of neuronal development. Each agent was introduced at 30 microM for 24 or 72 h, treatments devoid of cytotoxicity.

Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex.

To separate the direct pharmacological effects of cocaine from those associated with active drug self-administration we employed a yoked control-operant paradigm and investigated the expression of well established markers of the rapid action of cocaine, i.e. the inducible early genes Arc and Zif268 and trophic factors, i.

Neurotrophic factors in neurodegenerative disorders : potential for therapy.

Finding an effective therapy to treat chronic neurodegenerative disorders still represents an unmet and elusive goal, mainly because so many pathogenic variables come into play in these diseases. Recent emphasis has been placed on the role of neurotrophic factors in the aetiology of such disorders because of their role in the survival of different cell phenotypes under various adverse conditions, including neurodegeneration.This review summarizes the current status and the efforts to treat neurodegenerative disorders by the exogenous administration of neurotrophic factors in an attempt to replenish trophic supply, the paucity of which may contribute to the development of the illness.

Antipsychotic drugs modulate Arc expression in the rat brain.

We found that, in the striatum, acute injections of the first generation antipsychotic (FGA) haloperidol or the second generation antipsychotic (SGA) olanzapine enhanced Arc mRNA levels, however such induction persisted for at least 2 h in haloperidol-treated rats whereas it waned as early as 1 h after olanzapine injection. Conversely, repeated injections led to a persistent decrease of striatal Arc gene expression, regardless of the agent examined. In the frontal cortex, acute injection of both antipsychotics caused a reduction of Arc mRNA levels which persisted for at least 2 h.

Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation.

Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder resulting from the inherited deficiency of the arylsulfatase A (ARSA) enzyme. Currently, no valid therapeutic options are available for affected patients. A thorough knowledge of disease progression in its diverse clinical variants, together with the identification of reliable prognostic factors, could be instrumental in accurate patient selection for new upcoming therapeutic opportunities, such as enzyme replacement and gene therapy.

Levocetirizine in persistent allergic rhinitis: continuous or on-demand use? A pilot study.

Background: Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome.

Methods: The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis.