1,721,269 research outputs found
The impact of stress on neuronal plasticity: Implications for pathogenesis and treatment of psychiatric diseases
No full textMicroRNAs and psychiatric disorders : from aetiology to treatment
No full textThe emergence of psychiatric disorders relies on the interaction between genetic vulnerability and environmental adversities. Several studies have demonstrated a crucial role for epigenetics (e.g. DNA methylation, post-translational histone modifications and microRNA-mediated post-transcriptional regulation) in the translation of environmental cues into adult behavioural outcome, which can prove to be harmful thus increasing the risk to develop psychopathology. Within this frame, non-coding RNAs, especially microRNAs, came to light as pivotal regulators of many biological processes occurring in the Central Nervous System, both during the neuronal development as well as in the regulation of adult function, including learning, memory and neuronal plasticity. On these basis, in recent years it has been hypothesised a central role for microRNA modulation and expression regulation in many brain disorders, including neurodegenerative disorders and mental illnesses. Indeed, the aim of the present review is to present the most recent state of the art regarding microRNA involvement in psychiatric disorders. We will first describe the mechanisms that regulate microRNA biogenesis and we will report evidences of microRNA dysregulation in peripheral body fluids, in postmortem brain tissues from patients suffering from psychopathology as well as in animal models. Last, we will discuss the potential to consider microRNAs as putative target for pharmacological intervention, using common psychotropic drugs or more specific tools, with the aim to normalize functions that are disrupted in different psychiatric conditions
CREB, neurogenesis and depression
No full textThe transcription factor CREB has been implicated in signalling pathways relevant for pathogenesis and therapy of depression. CREB is upregulated and activated in the hippocampus by chronic antidepressant treatment, similarly as neurogenesis. Surprisingly, a recent study using CREB-deficient mice also demonstrates an upregulation of neurogenesis correlating with an antidepressant behavioral phenotype.((1)) Interestingly, CREB-deficient mice show a rapid behavioral response to antidepressants, while wild-type mice do not. This minireview tries to reconcile these new findings with established concepts on CREB, neurogenesis and depression. It also outlines some crucial experiments and lines of future research that could clarify some of the pending question
The preclinical profile of lurasidone: clinical relevance for the treatment of schizophrenia
No full textINTRODUCTION: Lurasidone is a novel antipsychotic drug approved for the treatment of schizophrenia in adults. It is formulated into tablets, administered orally once/day (dose range 40-160 mg/day) does not require titration, but needs to be given with food to maximize its plasma exposure.
AREAS COVERED: This review focuses on the preclinical discovery of lurasidone. Furthermore, the article provides analysis on the pharmacological, behavioral and molecular mechanisms of lurasidone and their contribution to its therapeutic advantages. The article is based on the literature reported in published preclinical and clinical studies, product labels, poster presentations and press releases.
EXPERT OPINION: Lurasidone demonstrated high affinity for serotonin 5-HT(1A), 5-HT(2A), 5-HT7, dopamine D2 and adrenergic α(2C) receptors followed by α1 and α(2A) receptors. The drug was active in animal models predictive of antipsychotic and antidepressant activities. In addition, it demonstrated procognitive effects, as it was effective in several animal models that assessed memory, cognition and executive functions in rats and in primates. At a cellular level, lurasidone promotes neuronal plasticity, can modulate epigenetic mechanisms controlling gene transcription, and increases the expression of the neurotrophic factor BDNF in cortical and limbic brain regions. Lurasidone's mechanisms of action might contribute to its unique psychopharmacological properties in the improved treatment of schizophrenia, and perhaps other psychiatric disorders
Chronic antidepressant treatments induces specific changes in BDNF expression and subcellular localization
No full textSynaptic alterations associated with depression and schizophrenia: potential as a therapeutic target
No full textIn recent years, the concept of 'synaptopathy' has been extended from neurodegenerative and neurological disorders to psychiatric diseases. According to this nascent line of research, disruption in synaptic structure and function acts as the main determinant of mental illness. Therefore, molecular systems and processes crucial for synaptic activity may represent promising therapeutic targets.
We review data on synaptic structural alterations in depression and schizophrenia and on specific molecular systems and/or mechanisms important for the maintenance of proper synaptic function. Specifically, we examine the involvement of the neuroligin system, the local protein translation, and the neurotrophin BDNF by reviewing clinical and preclinical studies, with particular attention to results provided by using animal models based on the role of stress in psychiatric diseases. Finally, we also discuss the impact of pharmacological treatment on these molecular systems/mechanisms.
The relevance of synaptic dysfunctions in psychiatric diseases is undoubted and the potential to normalize, ameliorate, and shape such alterations by acting on molecular systems crucial to ensure synaptic function property is fascinating. However, future studies are required to elucidate several open issues
L-deprenyl potentiates cAMP-induced elevation of FGF-2 mRNA levels in rat cortical astrocytes
No full textThe expression of fibroblast growth factor-2 (FGF-2, basic FGF) is up- regulated in astroglial cells by different stimuli, including glucocorticoid hormones and agents that cause an increase in cyclic AMP (cAMP) levels. In the present study we showed that L-deprenyl, a drug able to rescue neurons from potentially lethal damage, can potentiate FGF-2 induction by 8Br-cAMP in cultured astrocytes. This effect appears to be independent from its well known inhibitory activity on monoamine oxidase (MAO) type B. As astrocyte activation is an important step in response to neuronal injury, our data suggest that potentiation of neurotrophic factor expression may exert neuroprotection and therefore limit the progression of neuronal damage in several pathological situations
Transcriptional and translational changes of activity-regulated cytoskeletal associated protein following duloxetine treatment
No full textAnatomical specificity in the modulation of activity-regulated genes after acute or chronic lurasidone treatment
No full textLurasidone is a novel second generation antipsychotic drug characterized by a multi-receptor profile. Besides the high affinity for 5-HT2A and D2 receptors, it is also characterized by potent 5-HT7 receptor antagonism, which may be beneficial for mood and cognition. Considering that dose-dependent changes in receptor occupancy may differentially impact gene transcription, we aimed at investigating the effects of acute and chronic treatments with different doses of lurasidone (1, 3 and 10mg/kg) in rats on the expression of the activity-regulated genes Arc, Zif268 and Npas4, which are markers of neuronal activation and are also associated with neuroadaptive mechanisms. Our results show dose-dependent and anatomically-selective differences after acute and chronic lurasidone treatment. Indeed, the effects produced by acute treatment seem to reflect the modulatory activity of lurasidone at selected neurotransmitter receptors. In fact, low doses of the drug acted in the hippocampus, while high doses acted in the striatum, reflecting the high predominance of D2 receptor expression in this brain region. On the contrary, chronic treatment with lurasidone revealed a different profile of IEGs modulation, possibly reflecting neuroadaptive changes set in motion in response to repetitive drug exposure. In summary, the multi-receptor profile of lurasidone leads to the recruitment of different brain structures in a dose-related manner and this may be important for its therapeutic properties, particularly with respect to antidepressant activity and cognition
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