353 results on '"Sala, Mariaelvina"'
Search Results
102. Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils
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Braida, Daniela, primary, Pegorini, Simona, additional, Arcidiacono, Maria Vittoria, additional, Consalez, Gian Giacomo, additional, Croci, Laura, additional, and Sala, Mariaelvina, additional
- Published
- 2003
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103. Role of the endocannabinoid system in MDMA intracerebral self-administration in rats
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Braida, Daniela, primary and Sala, Mariaelvina, additional
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- 2002
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104. Involvement of CDC25Mm/Ras-GRF1-Dependent Signaling in the Control of Neuronal Excitability
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Tonini, Raffaella, primary, Franceschetti, Silvana, additional, Parolaro, Daniela, additional, Sala, Mariaelvina, additional, Mancinelli, Enzo, additional, Tininini, Silvia, additional, Brusetti, Ronny, additional, Sancini, Giulio, additional, Brambilla, Riccardo, additional, Martegani, Enzo, additional, Sturani, Emmapaola, additional, and Zippel, Renata, additional
- Published
- 2001
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105. CP 55,940 protects against ischemia-induced electroencephalographic flattening and hyperlocomotionin Mongolian gerbils
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Braida, Daniela, primary, Pozzi, Morena, additional, and Sala, Mariaelvina, additional
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- 2000
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106. Cannabinoid-induced working memory impairment is reversed by a second generation cholinesterase inhibitor in rats
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Braida, Daniela, primary and Sala, Mariaelvina, additional
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- 2000
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107. In vivo characterization of the specific cannabinoid receptor antagonist, SR141716A: Behavioral and cellular responses after acute and chronic treatments
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Rubino, Tiziana, primary, Vigan�, Daniela, additional, Zagato, Elisabetta, additional, Sala, Mariaelvina, additional, and Parolaro, Daniela, additional
- Published
- 2000
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108. A novel method for self-administering addicting drugs intracerebroventricularly in a free-choice procedure
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Braida, Daniela, primary, Virag, Walter, additional, Ottonello, Francesco, additional, Inghilterra, Salvatore, additional, Gori, Enzo, additional, and Sala, Mariaelvina, additional
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- 1998
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109. Long-Lasting Antiamnesic Effect of a Novel Anticholinesterase Inhibitor (MF268)
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Braida, Daniela, primary, Paladini, Emma, additional, Griffini, Pierluigi, additional, Lamperti, Mariapia, additional, Colibretti, Luisa, additional, and Sala, Mariaelvina, additional
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- 1998
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110. Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil
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Sala, Mariaelvina, primary, Leone, Maria Primula, additional, Lampugnani, Paola, additional, Matturri, Luigi, additional, and Gori, Enzo, additional
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- 1997
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111. An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats: comparison with other cholinesterase inhibitors
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Braida, Daniela, primary, Paladini, Emma, additional, Griffini, Pierluigi, additional, Lamperti, Mariapia, additional, Maggi, Antonio, additional, and Sala, Mariaelvina, additional
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- 1996
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112. Eeg power spectra and behavioural correlates in rats given chronic morphine. lack of residual long-term eeg and neuronal changes
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Sala, Mariaelvina, primary, Leone, Maria Primula, additional, Lampugnani, Paola, additional, Braida, Daniela, additional, Frattola, Danila, additional, and Gori, Enzo, additional
- Published
- 1995
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113. Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat
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Sala, Mariaelvina, primary, Leone, Maria Primula, additional, Lampugnani, Paola, additional, Braida, Daniela, additional, and Gori, Enzo, additional
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- 1995
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114. Relationship between morphine and etonitazene-induced working memory impairment and analgesia
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Braida, Daniela, primary, Gori, Enzo, additional, and Sala, Mariaelvina, additional
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- 1994
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115. Possibility of Spontaneous Drug Abuse Tested in Rat
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Sala, Mariaelvina, primary, Braida, Daniela, additional, Calcaterra, Paola, additional, Leone, Maria Primula, additional, and Gori, Enzo, additional
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- 1993
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116. Dose-dependent conditioned place preference produced by etonitazene and morphine
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Sala, Mariaelvina, primary, Braida, Daniela, additional, Calcaterra, Paola, additional, Leone, Maria Primula, additional, and Gori, Enzo, additional
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- 1992
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117. Neurohypophyseal hormones manipulation modulate social and anxiety-related behavior in zebrafish.
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Braida, Daniela, Donzelli, Andrea, Martucci, Roberta, Capurro, Valeria, Busnelli, Marta, Chini, Bice, and Sala, Mariaelvina
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VASOPRESSIN ,OXYTOCIN ,SOCIAL anxiety ,BRAIN diseases ,NEUROPEPTIDES ,INTERPERSONAL relations ,LABORATORY zebrafish - Abstract
Rationale: Oxytocin (OT) and arginine-vasopressin (AVP) regulate social behavior in mammals. Zebrafish ( Danio rerio) allows higher throughput and ease in studying human brain disorders. Objectives: This study investigated in zebrafish the effect of non-mammalian homologs isotocin (IT) and vasotocin (AVT) in comparison with OT/AVP on social behavior and fear response to predator. The mechanism was studied using the most human selective OT and AVP receptor antagonists. Methods: Zebrafish were injected i.m. with increasing doses (0.001-40 ng/kg) of the neuropeptides. DesGly-NH- d(CH)-[ d-Tyr,Thr]OVT) for OT receptor, SR 49059 for V1a subtype receptor, and SSR-149415 for V1b subtype receptor were injected i.m. 10 min before each agonist. Results: All the peptides increased social preference and reduced fear to predator response in a dose-dependent manner interpolated by symmetrical parabolas. AVT/AVP were more potent to elicit anxiolytic than social effect while IT and OT were equally potent. All the antagonists dose-dependently inhibited both the effects induced by the neuropeptides. The ratio between the ED50 obtained for blocking the OT-induced effects on social preference and fear response to predator was very high only for desglyDTTyrOVT (160). SR49059 showed the highest ratio in blocking AVP-induced effects (807). The less selective antagonist appeared to be SSR149415. Conclusions: For the first time, IT/AVT and OT/AVP were found to modulate in zebrafish, social behavior, unrelated to sex, and fear to predator response through at least two different receptors. Zebrafish is confirmed as a valid, reliable model to study deficit in social behavior characteristic of some psychiatric disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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118. Effect of centrally administered atropine and pirenzepine on radial arm maze performance in the rat
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Sala, Mariaelvina, primary, Braida, Daniela, additional, Calcaterra, Paola, additional, Primula Leone, Maria, additional, Arianna Comotti, Franca, additional, Gianola, Silvia, additional, and Gori, Enzo, additional
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- 1991
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119. Chronic Δ9 -Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates.
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Rubino, Tiziana, Vigano, Daniela, Realini, Natalia, Guidali, Cinzia, Braida, Daniela, Capurro, Valeria, Castiglioni, Chiara, Cherubino, Francesca, Romualdi, Patrizia, Candeletti, Sanzio, Sala, Mariaelvina, and Parolaro, Daniela
- Abstract
Few and often contradictory reports exist on the long-term neurobiological consequences of cannabinoid consumption in adolescents. The endocannabinoid system plays an important role during the different stages of brain development as cannabinoids influence the release and action of different neurotransmitters and promote neurogenesis. This study tested whether long-lasting interference by cannabinoids with the developing endogenous cannabinoid system during adolescence caused persistent behavioral alterations in adult rats. Adolescent female and male rats were treated with increasing doses of Δ
9 -tetrahydrocannabinol (THC) for 11 days (postnatal day (PND) 35–45) and left undisturbed until adulthood (PND 75) when behavioral and biochemical assays were carried out. CB1 receptor level and CB1/G-protein coupling were significantly reduced by THC exposure in the amygdala (Amyg), ventral tegmental area (VTA) and nucleus accumbens (NAc) of female rats, whereas male rats had significant alterations only in the amygdala and hippocampal formation. Neither female nor male rats showed any changes in anxiety responses (elevated plus maze and open-field tests) but female rats presented significant ‘behavioral despair’ (forced swim test) paralleled by anhedonia (sucrose preference). In contrast, male rats showed no behavioral despair but did present anhedonia. This different behavioral picture was supported by biochemical parameters of depression, namely CREB alteration. Only female rats had low CREB activity in the hippocampal formation and prefrontal cortex and high activity in the NAc paralleled by increases in dynorphin expression. These results suggest that heavy cannabis consumption in adolescence may induce subtle alterations in the emotional circuit in female rats, ending in depressive-like behavior, whereas male rats show altered sensitivity to rewarding stimu. [ABSTRACT FROM AUTHOR]- Published
- 2008
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120. Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats.
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Rubino, Tiziana, Sala, Mariaelvina, Viganò, Daniela, Braida, Daniela, Castiglioni, Chiara, Limonta, Valeria, Guidali, Cinzia, Realini, Natalia, and Parolaro, Daniela
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TETRAHYDROCANNABINOL , *ANXIETY , *PREFRONTAL cortex , *CELLULAR mechanics , *NEUROPHARMACOLOGY , *LABORATORY rats - Abstract
We investigated the effect of low doses of intraperitoneal Δ9-tetrahydrocannabinol (THC) on anxiety behavior in rats using the elevated plus maze (EPM). An anxiolytic effect was obtained in a range of doses between 0.075 and 1.5 mg/kg, the 0.75 dose being the most effective. Pretreatment with the CB1 receptor antagonist AM251 fully reversed THC's effect, suggesting CB1 receptors were involved. In order to elucidate the neuroanatomical substrates underlying the effect of the maximal effective dose of THC, we investigated cFos expression in anxiety-related brain regions (prefrontal cortex, nucleus accumbens, amygdala, and hippocampus) of rats exposed to the EPM. THC significantly lowered the amount of cFos in prefrontal cortex and amygdala without affecting the other cerebral areas. As there is increasing evidence that CREB function regulates anxiety-like behavior in rats, the second biochemical parameter we measured was phosphorylated CREB in the same brain areas. Rats treated with THC showed a significant increase in CREB activation in the prefrontal cortex and hippocampus. In the prefrontal cortex this increased activation was linked to an increase in ERK activation, whereas in the hippocampus there was a drop in the activity of CAMKII, a kinase with inhibitory effect on CREB activation. All these effects were reversed by AM251 pretreatment, suggesting that stimulation of CB1 receptors is fundamental for triggering the biochemical events. Our results suggest that the stimulation of these receptors in the prefrontal cortex, amygdala, and hippocampus with the subsequent activation of different signaling pathways is the first event underlying the effects of cannabinoids on anxious states.Neuropsychopharmacology (2007) 32, 2036–2045; doi:10.1038/sj.npp.1301330; published online 7 February 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
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121. Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement.
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Braida, Daniela, Limonta, Valeria, Pegorini, Simona, Zani, Alessia, Guerini-Rocco, Chiara, Gori, Enzo, and Sala, Mariaelvina
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SALVINORIN A ,SALVIA divinorum ,HALLUCINATIONS ,HALLUCINOGENIC drugs ,FISH behavior ,FISH locomotion ,FISH as laboratory animals - Abstract
The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals. The effects of salvinorin A on the zebrafish ( Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied. Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1–10 μg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 μg/kg) or vehicle and evaluated in a two-compartment chamber. Salvinorin A (0.1 and 0.2 μg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a “trance-like” effect, at doses as 5 and 10 μg/kg, was obtained. Pretreatment with the κ-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB
1 ) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 μg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 μg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 μg/kg produced no effect, whereas a dose of 80 μg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 μg/kg). Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both κ-opioid and cannabinoid CB1 receptors. [ABSTRACT FROM AUTHOR]- Published
- 2007
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122. Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain.
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Ferri, Anna L. M., Cavallaro, Maurizio, Braida, Daniela, Cristofano, Antonello Di, Canta, Annalisa, Vezzani, Annamaria, Ottolenghi, Sergio, Pandolfi, Pier Paolo, Sala, Mariaelvina, DeBiasi, Silvia, and Nicolis, Silvia K.
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STEM cells ,NEURAL stem cells ,MICE ,NEURODEGENERATION ,DEVELOPMENTAL neurobiology - Abstract
In many species, the Sox2 transcription factor is a marker of the nervous system from the beginning of its development, and we have previously shown that Sox2 is expressed in embryonic neural stem cells. It is also expressed in, and is essential for, totipotent inner cell mass stem cells and other multipotent cell lineages, and its ablation causes early embryonic lethality. To investigate the role of Sox2 in the nervous system, we generated different mouse mutant alleles: a null allele (Sox2
βgeo 'knock-in'), and a regulatory mutant allele (Sox2ΔENH ), in which a neural cell-specific enhancer is deleted. Sox2 is expressed in embryonic early neural precursors of the ventricular zone and, in the adult, in ependyma (a descendant of the ventricular zone). It is also expressed in the vast majority of dividing precursors in the neurogenic regions, and in a small proportion of differentiated neurones, particularly in the thalamus, striatum and septum. Compound SOX2β-geo/ΔENH heterozygotes show important cerebral malformations, with parenchymal loss and ventricle enlargement, and L-dopa-rescuable circling behaviour and epilepsy. We observed striking abnormalities in neurones; degeneration and cytoplasmic protein aggregates, a feature common to diverse human neurodegenerative diseases, are observed in thalamus, striatum and septum. Furthermore, ependymal cells show ciliary loss and pathological lipid inclusions. Finally, precursor cell proliferation and the generation of new neurones in adult neurogenic regions are greatly decreased, and GFAP/nestin-positive hippocampal cells, which include the earliest neurogenic precursors, are strikingly diminished. These findings highlight a crucial and unexpected role for Sox2 in the maintenance of neurones in selected brain areas, and suggest a contribution of neural cell proliferative defects to the pathological phenotype. [ABSTRACT FROM AUTHOR]- Published
- 2004
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123. Eptastigmine: Ten Years of Pharmacology, Toxicology, Pharmacokinetic, and Clinical Studies.
- Author
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Braida, Daniela and Sala, Mariaelvina
- Abstract
ABSTRACT Eptastigmine (heptyl-physostigmine tartrate) is a carbamate derivative of physostigmine in which the carbamoylmethyl group in position 5 of the side chain has been substituted with a carbamoylheptyl group. In vitro and ex vivo results suggest that eptastigmine has a long-lasting reversible brain cholinesterase (i.e., acetylcholinesterase and butyrylcholinesterase) inhibitory effect. When administered in vivo to rodents by various routes, eptastigmine inhibits cerebral acetylcholinesterases (AChE) and increases acetylcholine (Ach) brain levels by 2500-3000%, depending on the dose. This effect leads to an improvement in the cerebral blood flow in the ischemic brain, excitatory and inhibitory effects on the gastrointestinal tract and to a protection from acute soman and diisopropylflu-orophosphate intoxication. Eptastigmine, by either acute or chronic administration, has been found to have memory enhancing effects in different species of normal, aged and lesioned animals. It also restored to normal the age-related increase of EEG power without affecting spontaneous motor activity. Clinical investigations on more than 1500 patients with Alzheimer's disease demonstrated that eptastigmine significantly improved cognitive performance (as assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale) as compared with placebo. This improvement was most evident in patients with more severe cognitive impairment at the baseline. The relationship between patient performance and average steady-state AChE inhibition was described by an inverted U-shaped dose-response curve. Pharmacokinetic studies have revealed that after oral administration eptastigmine is rapidly distributed to the tissues and readily enters the CNS, where it can be expected to inhibit AChE for a prolonged period. Eptastigmine is generally well tolerated and the majority of adverse events (cholinergic) were mild to moderate in intensity. However, the adverse hematologic (granulocytopenia) effects reported in two studies have resulted in the suspension of further clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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124. Cannabinoidinduced working memory impairment is reversed by a second generation cholinesterase inhibitor in rats
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Braida, Daniela and Sala, Mariaelvina
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Cannabinoids which impair rat working memory appear to inhibit hippocampal extracellular acetylcholine (Ach) release and reduce choline uptake through an interaction with CB1cannabinoid receptors. Here we report that CP 55,940, a potent bicyclic synthetic cannabinoid analog, dose–dependently impaired rat performance, when given i.p. 20 min before an eight-arm radial maze test. The selective CB1cannabinoid receptor antagonist SR 141716A, given i.p. 20 min earlier, significantly reduced the memory deficit. Pretreatment with eptastigmine, a second generation cholinesterase inhibitor, given orally 100 min before the cannabinoid agonist, relieved the memory impairment without affecting CP 55,940-induced behavioural alterations such as reduced spontaneous motor activity, analgesia and hind limb splaying. These data suggest that cannabinoid-induced working memory impairment is mediated through a central cholinergic blockade.
- Published
- 2000
125. Different attentional dysfunctions in eEF2K−/−, IL1RAPL1−/− and SHANK3Δ11−/− mice.
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Ponzoni, Luisa, Sala, Carlo, Verpelli, Chiara, Sala, Mariaelvina, and Braida, Daniela
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KNOCKOUT mice ,DERMATOPHAGOIDES ,AUTISM spectrum disorders ,BEHAVIORAL assessment ,MICE ,NEUROPLASTICITY - Abstract
A common feature of several psychiatric disorders is the attentional impairment. eEF2K−/−, IL1RAPL1−/− and SHANK3Δ11−/− mice were used as animal models consistently linked to changes in synaptic plasticity, learning and memory. All knockout (KO) mice and their corresponding littermates were submitted to the novel object recognition (NOR) and visual object recognition (VOR) tasks. In the NOR, eEF2K−/− mice exhibited a normal performance in terms of mean discrimination index, while SHANK3Δ11−/− and IL1RAPL1−/− mice were impaired when a delay of 2 and 24 hours was introduced. Surprisingly, when submitted to VOR, where the two objects were replaced with two shapes delivered from two iPods, all the mutant mice performed worse than those in the NOR. In VOR, the application of motion to different shapes, to increase attention, improved performance in eEF2K−/− and IL1RAPL1−/− but not in SHANK3Δ11−/− mice. In SHANK3Δ11−/− mice, attentional deficit was also present even if different motions were applied to the same shapes or when these mice were repeatedly exposed for 5 days to the context. Behavioral analysis showed that eEF2K−/− and IL1RAPL1−/− mice had a good flexibility tested in the T‐maze. eEF2K−/− showed normal self‐grooming. On the basis of previous literature data indicating that SHANK3Δ11−/− showed impaired flexibility and reduced sociability, we identified in this genotype the most exhaustive model showing all the core symptoms of autism spectrum disorder including a heavy visual attention deficit. These findings show the importance of VOR to identify mouse models of autism. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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126. Epileptiform Activity and Cognitive Deficits in SNAP-25+/− Mice are Normalized by Antiepileptic Drugs
- Author
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Corradini, Irene, Donzelli, Andrea, Antonucci, Flavia, Welzl, Hans, Loos, Maarten, Martucci, Roberta, De Astis, Silvia, Pattini, Linda, Inverardi, Francesca, Wolfer, David Paul, Caleo, Matteo, Bozzi, Yuri, Verderio, Claudia, Frassoni, Carolina, Braida, Daniela, Clerici, Mario, Lipp, Hans-Peter, Sala, Mariaelvina, and Matteoli, Michela
- Subjects
Valproate ,Epilepsy ,Memory ,SNAP-25 ,3. Good health - Abstract
Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25+/−) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25+/− mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drugs., Cerebral Cortex, 24 (2), ISSN:1047-3211, ISSN:1460-2199
127. Epileptiform Activity and Cognitive Deficits in SNAP-25+/− Mice are Normalized by Antiepileptic Drugs
- Author
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Corradini, Irene, Donzelli, Andrea, Antonucci, Flavia, Welzl, Hans, Loos, Maarten, Martucci, Roberta, De Astis, Silvia, Pattini, Linda, Inverardi, Francesca, Wolfer, David, Caleo, Matteo, Bozzi, Yuri, Verderio, Claudia, Frassoni, Carolina, Braida, Daniela, Clerici, Mario, Lipp, Hans-Peter, Sala, Mariaelvina, Matteoli, Michela, Corradini, Irene, Donzelli, Andrea, Antonucci, Flavia, Welzl, Hans, Loos, Maarten, Martucci, Roberta, De Astis, Silvia, Pattini, Linda, Inverardi, Francesca, Wolfer, David, Caleo, Matteo, Bozzi, Yuri, Verderio, Claudia, Frassoni, Carolina, Braida, Daniela, Clerici, Mario, Lipp, Hans-Peter, Sala, Mariaelvina, and Matteoli, Michela
- Abstract
Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25+/−) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25+/− mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drugs
128. Effect of intracerebroventricular administration of morphine upon intestinal motility in rat and its antagonism with naloxone
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Parolaro, Daniela, primary, Sala, Mariaelvina, additional, and Gori, Enzo, additional
- Published
- 1977
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129. Intestinal effect and analgesia: Evidence for different involvement of opioid receptor subtypes in periaqueductal gray matter
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Parolaro, Daniela, primary, Crema, Giovanna, additional, Sala, Mariaelvina, additional, Santagostino, Angela, additional, Giagnoni, Gabriella, additional, and Gori, Enzo, additional
- Published
- 1986
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130. Involvement of periaqueductal gray matter in intestinal effect of centrally administered morphine
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Sala, Mariaelvina, primary, Parolaro, Daniela, additional, Crema, Giovanna, additional, Spazzi, Laura, additional, Giagnoni, Gabriella, additional, Cesana, Raffaele, additional, and Gori, Enzo, additional
- Published
- 1983
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131. Fluoxetine rescues the depressive-like behaviour induced by reserpine and the altered emotional behaviour induced by nicotine withdrawal in zebrafish: Involvement of tyrosine hydroxylase.
- Author
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Braida, Daniela, Ponzoni, Luisa, Dellarole, Ilaria, Morara, Stefano, and Sala, Mariaelvina
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ANTIDEPRESSANTS , *TYROSINE hydroxylase , *MENTAL depression , *RESERPINE , *ZEBRA danio , *FLUOXETINE , *BRACHYDANIO , *CALCITONIN gene-related peptide - Abstract
Background: Nicotine cessation leads to anxiety and depression. Aims: The suitability of the zebrafish model of anhedonia using reserpine and fluoxetine was evaluated. Fluoxetine was also used to reduce nicotine withdrawal-induced anhedonic state. Methods: Zebrafish were exposed to reserpine (40 mg/l) and then to fluoxetine (0.1 mg/l) for 1 week. Anhedonia was evaluated in the Novel Tank Diving and Compartment Preference tests. Another group was exposed to nicotine (1 mg/l/2 weeks) and then exposed to fluoxetine. Anxiety and anhedonia were evaluated 2–60 days after. Tyrosine hydroxylase (TH) immunoreactivity and microglial morphology (labelled by 4C4 monoclonal antibody) in the parvocellular pretectal nucleus (PPN), dorsal part, and of calcitonin gene-related peptide (CGRP) in the hypothalamus were also analysed. Results: Less time in the top and increased latency to the top in reserpine compared to a drug-free group was found. Fluoxetine rescued reserpine-induced the reduced time in the top. Seven and 30 days after nicotine withdrawal more time in the bottom and similar time in the Compartment Preference test, rescued by fluoxetine, were shown. In the PPN, 30-day withdrawal induced an increase in TH immunoreactivity, but fluoxetine induced a further significant increase. No changes in PPN microglia morphology and hypothalamic CGRP were detected. Conclusions: Our findings validate the suitability of the zebrafish model of anhedonia using the reserpine-induced depression-like behaviour and the predictivity using fluoxetine. Fluoxetine rescued nicotine withdrawal-induced anhedonic state, opening the possibility to screen new drugs to alleviate anxiety and depression in smokers during abstinence. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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132. Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission.
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Zapata, Jonathan, Moretto, Edoardo, Hannan, Saad, Murru, Luca, Longatti, Anna, Mazza, Davide, Benedetti, Lorena, Fossati, Matteo, Heise, Christopher, Ponzoni, Luisa, Valnegri, Pamela, Braida, Daniela, Sala, Mariaelvina, Francolini, Maura, Hildebrand, Jeffrey, Kalscheuer, Vera, Fanelli, Francesca, Sala, Carlo, Bettler, Bernhard, and Bassani, Silvia
- Abstract
Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABA
B receptors (GABAB Rs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABAB R activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABAB Rs and extrasynaptic δ-subunit-containing GABAA Rs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABAB R-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy. [ABSTRACT FROM AUTHOR]- Published
- 2017
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133. Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors.
- Author
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Ponzoni, Luisa, Daniela, Braida, and Sala, Mariaelvina
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ECSTASY (Drug) , *SEROTONIN receptors , *HALLUCINOGENIC drugs , *DRUG abuse , *PHENETHYLAMINES , *LABORATORY zebrafish - Abstract
Rationale: The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied. Objectives: Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT-like receptor on the abovementioned effects was evaluated. Methods: Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1-20 mg/kg), PMA (0.0005-2 mg/kg), or MDMA (0.5-160 mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT subtype receptor antagonist ritanserin (0.025-2.5 mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated. Results: MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2 mg/kg) and PMA (0.1 mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160 mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT subtype receptor. Conclusion: Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens. [ABSTRACT FROM AUTHOR]
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- 2016
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134. Increase of plasma corticosterone induced by loperamide in rats
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Giagnoni, Gabriella, Parolaro, Daniela, Sala, Mariaelvina, Marabini, Laura, Senini, Rosanna, and Gori, Enzo
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- 1982
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135. Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K).
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Beretta, Stefania, Gritti, Laura, Ponzoni, Luisa, Scalmani, Paolo, Mantegazza, Massimo, Sala, Mariaelvina, Verpelli, Chiara, and Sala, Carlo
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LABORATORY mice , *PROTHROMBIN , *ANIMAL disease models , *EPILEPSY , *ANTICONVULSANTS , *SODIUM channels - Abstract
Background: Dravet Syndrome is a severe childhood pharmaco-resistant epileptic disorder mainly caused by mutations in the SCN1A gene, which encodes for the α1 subunit of the type I voltage-gated sodium channel (NaV1.1), that causes imbalance between excitation and inhibition in the brain. We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a ± mice, a murine model of Dravet Syndrome. Methods: To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a ± mice. By crossing Scn1a ± mice with eEF2K−/− mice we obtained the three main genotypes needed for our studies, Scn1a+/+ eEF2K+/+ (WT mice), Scn1a ± eEF2K+/+ mice (Scn1a ± mice) and Scn1a ± eEF2K−/− mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a ± mice. Results: We showed that the activity of eEF2K/eEF2 pathway was enhanced in Scn1a ± mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a ± mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a ± mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses. Limitations: Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a ± needs further investigations. Conclusions: Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome. [ABSTRACT FROM AUTHOR]
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- 2022
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136. Behavioural and pharmacological profiles of zebrafish administrated pyrrolidinyl benzodioxanes and prolinol aryl ethers with high affinity for heteromeric nicotinic acetylcholine receptors.
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Braida, Daniela, Ponzoni, Luisa, Moretti, Milena, Viani, Paola, Pallavicini, Marco, Bolchi, Cristiano, Appiani, Rebecca, Bavo, Francesco, Gotti, Cecilia, and Sala, Mariaelvina
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NICOTINIC acetylcholine receptors , *ETHERS , *CHOLINERGIC receptors , *ELECTROPHYSIOLOGY , *NICOTINE , *NICOTINIC receptors - Abstract
Rationale: Prolinol aryl ethers and their rigidified analogues pyrrolidinyl benzodioxanes have a high affinity for mammalian α4β2 nicotinic acetylcholine receptors (nAChRs). Electrophysiological studies have shown that the former are full agonists and the latter partial agonists or antagonists of human α4β2 receptors, but their in vivo effects are unknown. Objectives and methods: As α4β2 nAChRs play an important role in the cognition and the rewarding effects of nicotine, we tested the effects of two full agonists and one antagonist on spatial learning, memory and attention in zebrafish using a T-maze task and virtual object recognition test (VORT). The effect of a partial agonist in reducing nicotine-induced conditioned place preference (CPP) was also investigated. Results: In comparison with the vehicle alone, the full agonists MCL-11 and MCL-28 induced a significant cognitive enhancement as measured by the reduced running time in the T-maze and increased attention as measured by the increased discrimination index in the VORT. MCL-11 was 882 times more potent than nicotine. The two compounds were characterised by an inverted U-shaped dose-response curve, and their effects were blocked by the co-administration of the antagonist MCL-117, which alone had no effect. The partial agonist MCL-54 induced CPP and had an inverted U-shaped dose-response curve similar to that of nicotine but blocked the reinforcing effect of co-administered nicotine. Binding studies showed that all of the compounds have a higher affinity for heteromeric [3H]-epibatidine receptors than [125I]-αBungarotoxin receptors. MCL-11 was the most selective of heteromeric receptors. Conclusions: These behavioural studies indicate that full agonist prolinol aryl ethers are very active in increasing spatial learning, memory and attention in zebrafish. The benzodioxane partial agonist MCL-54 reduced nicotine-induced CPP, and the benzodioxane antagonist MCL-117 blocked all agonist-induced activities. [ABSTRACT FROM AUTHOR]
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- 2020
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137. Increased sensitivity to Δ9-THC-induced rewarding effects after seven-week exposure to electronic and tobacco cigarettes in mice.
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Ponzoni, Luisa, Moretti, Milena, Braida, Daniela, Zoli, Michele, Clementi, Francesco, Viani, Paola, Sala, Mariaelvina, and Gotti, Cecilia
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TOBACCO , *ELECTRONIC cigarettes , *PASSIVE smoking , *SMOKING cessation , *AMPA receptors , *MICE - Abstract
Abstract Cigarette (CIG) smoking often precedes the use of illegal drugs. Electronic-cigarettes (e-CIGs) have been promoted as a means of stopping smoking and reducing the harmful effects of CIGs on the population. However, although e-CIGs eliminate some of the morbidity associated with combustible tobacco, they are still nicotine-delivery devices. In order to study whether the nicotine delivered via e-CIG acts as "a gateway drug" to the use of cannabis, we analysed the behavioural and molecular effects of 7 weeks' pre-exposure to air (AIR), e-CIGs or CIGs on addiction-related conditioned place preference (CPP) in mice using a sub-threshold (0.01 mg/kg) dose of delta-9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of cannabis. After 8 and 66 days of withdrawal, this Δ9-THC dose was ineffective in inducing CPP in mice pre-exposed to pump-driven AIR, but very effective in mice pre-exposed to e-CIGs or CIGs. Exposure to e-CIGs or CIGs increases the expression of ΔFosB in the nucleus accumbens (NAc), which remains high during short-term e-CIG or CIG withdrawal and long-term CIG withdrawal and is not influenced by treatment with Δ9-THC. At the end of e-CIG or CIG exposure and during withdrawal, the mice also had a higher AMPA receptors GluA1/GluA2-3 ratio in the NAc. Chronic nicotine exposure increases sensitivity to rewarding effects of Δ9-THC in mice and produces long-lasting neurobiological changes regardless of the delivery method (CIG vs. e-CIG). The exposure to passive tobacco smoke or e-CIG vapours can similarly increase vulnerability to the effects of cannabis and possibly other drugs of abuse. [ABSTRACT FROM AUTHOR]
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- 2019
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138. In vivo and in vitro ADMET profiling and in vivo pharmacodynamic investigations of a selective α7 nicotinic acetylcholine receptor agonist with a spirocyclic Δ2-isoxazoline molecular skeleton.
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Matera, Carlo, Dondio, Giulio, Braida, Daniela, Ponzoni, Luisa, De Amici, Marco, Sala, Mariaelvina, and Dallanoce, Clelia
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ISOXAZOLINE , *NICOTINIC acetylcholine receptors , *PHARMACODYNAMICS , *BIOLOGICAL assay , *CENTRAL nervous system - Abstract
(±)-3-Methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate (±)-1 was previously characterized as the most selective agonist at α7 neuronal nicotinic acetylcholine receptors in a series of spirocyclic quinuclidinyl-Δ 2 -isoxazoline derivatives. In this study, we performed different in vitro biological assays aimed at characterizing the ADMET properties of (±)-1. Then, we tested the compound in vivo in behavioral studies including classical novel object recognition and inhibitory avoidance tests in the rat, and a spatial memory assay in zebrafish involving a rapid T-maze task. The results indicated an overall favorable profile for (±)-1 in view of potential therapeutic applications targeting the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2018
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139. LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior.
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Rusconi, Francesco, Grillo, Barbara, Ponzoni, Luisa, Bassani, Silvia, Toffolo, Emanuela, Paganini, Leda, Mallei, Alessandra, Braida, Daniela, Passafaro, Maria, Popoli, Maurizio, Sala, Mariaelvina, and Battaglioli, Elena
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EPIGENETICS , *GENE expression , *GENETIC regulation , *LYSINE specific demethylase 1 , *DEMETHYLASE - Abstract
Behavioral changes in response to stressful stimuli can be controlled via adaptive epigenetic changes in neuronal gene expression. Here we indicate a role for the transcriptional corepressor Lysine-Specific Demethylase 1 (LSD1) and its dominant-negative splicing isoform neuroLSD1, in the modulation of emotional behavior. In mouse hippocampus, we show that LSD1 and neuroLSD1 can interact with transcription factor serum response factor (SRF) and set the chromatin state of SRF-targeted genes early growth response 1 (egr1) and c-fos. Deletion or reduction of neuroLSD1 in mutant mice translates into decreased levels of activating histone marks at egr1 and c-fos promoters, dampening their psychosocial stress-induced transcription and resulting in low anxiety-like behavior. Administration of suberoylanilide hydroxamine to neuroLSD1KO mice reactivates egr1 and c-fos transcription and restores the behavioral phenotype. These findings indicate that LSD1 is a molecular transducer of stressful stimuli as well as a stress-response modifier. Indeed, LSD1 expression itself is increased acutely at both the transcriptional and splicing levels by psychosocial stress, suggesting that LSD1 is involved in the adaptive response to stress. [ABSTRACT FROM AUTHOR]
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- 2016
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140. Spontaneous object and movement representations in 4-month-old human infants and albino Swiss mice.
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Langus, Alan, Saksida, Amanda, Braida, Daniela, Martucci, Roberta, Sala, Mariaelvina, and Nespor, Marina
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INFANT psychology , *LABORATORY mice , *VISUAL perception , *RECOGNITION (Psychology) , *MENTAL representation - Abstract
Can young infants decompose visual events into independent representations of objects and movements? Previous studies suggest that human infants may be born with the notion of objects but there is little evidence for movement representations during the first months of life. We devised a novel Rapid Visual Recognition Procedure to test whether the nervous system is innately disposed for the conceptual decomposition of visual events. We show that 4-month-old infants can spontaneously build object and movement representations and recognize these in partially matching test events. Also albino Swiss mice that were tested on a comparable procedure could spontaneously build detailed mental representations of moving objects. Our results dissociate the ability to conceptually decompose physical events into objects and spatio-temporal relations from various types of human and non-human specific experience, and suggest that the nervous system is genetically predisposed to anticipate the representation of objects and movements in both humans and non-human species. [ABSTRACT FROM AUTHOR]
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- 2015
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141. The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine receptors.
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Ponzoni, Luisa, Braida, Daniela, Pucci, Luca, Andrea, Donzelli, Fasoli, Francesca, Manfredi, Irene, Papke, Roger, Stokes, Clare, Cannazza, Giuseppe, Clementi, Francesco, Gotti, Cecilia, and Sala, Mariaelvina
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NICOTINIC receptors , *ZEBRA danio , *CYTISINE , *ANTISEPTICS , *LIGANDS (Biochemistry) , *REWARD (Psychology) , *SMOKING cessation - Abstract
Rationale: Cigarette smoking is one of the most serious health problems worldwide and people trying to stop smoking have high rates of relapse. Zebrafish ( Danio rerio), by combining pharmacological and behavioral assays, is a promising animal model for rapidly screening new compounds to induce smoking cessation. Objectives: This study aims to identify possible acetylcholine nicotinic receptors (nAChRs) involved in mediating nicotine (NIC)-induced conditioned place preference (CPP) in zebrafish and investigate the effect of the CC4 and CC26 cytisine derivatives in reducing NIC-induced CPP. Methods: CPP was evaluated using a two-compartment chamber, and the zebrafish were given CC4 (0.001-5 mg/kg), CC26 (0.001-1 mg/kg), cytisine (0.1-2.5 mg/kg), and varenicline (1-10 mg/kg) alone or with NIC (0.001 mg/kg). Swimming activity was evaluated using a square observational chamber. The affinity of the nicotinic ligands for native zebrafish brain nAChRs was evaluated by binding studies using [H]-Epibatidine (Epi) and [I]-αBungarotoxin (αBgtx) radioligands, and their subtype specificity was determined by means of electrophysiological assay of oocyte-expressed α4β2 and α7 subtypes. Results: CC4 and CC26 induced CPP with an inverted U-shaped dose-response curve similar to that of NIC. However, when co-administered with NIC, they blocked its reinforcing or slightly aversive effect. Binding and electrophysiological studies showed that this effect was due to binding to high-affinity heteromeric but not α7-containing receptors. Conclusions: We have further characterized CC4 and identified a new compound (CC26) that may be active in inducing smoking cessation. Zebrafish is a very useful model for screening new compounds that can affect the rewarding properties of NIC. [ABSTRACT FROM AUTHOR]
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- 2014
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142. A new model to study visual attention in zebrafish.
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Braida, Daniela, Ponzoni, Luisa, Martucci, Roberta, and Sala, Mariaelvina
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VISUAL perception , *LABORATORY zebrafish , *COGNITIVE ability , *RECOGNITION (Psychology) , *COGNITION disorders , *MECAMYLAMINE , *THERAPEUTICS - Abstract
The major part of cognitive tasks applied to zebrafish has not fully assessed their attentional ability, a process by which the nervous system learns, organizes sensory input and generates coordinated behaviour. In an attempt to maximize the value of zebrafish as an animal model of cognition, we tested the possibility to apply a modified version of novel object recognition test named virtual object recognition test (VORT) using 2D geometrical shapes (square, triangle, circle, cross, etc.) on two iPod 3.5-inch widescreen displays, located on two opposite walls of the water tank. Each fish was subjected to a familiarization trial (T 1 ), and after different time delays (from 5 min to 96 h) to a novel shape recognition trial (T 2 ). A progressive decrease, across time, of memory performance, in terms of mean discrimination index and mean exploration time, was shown. The predictive validity was tested using cholinergic drugs. Nicotine (0.02 mg/kg intraperitoneally, IP) significantly increased, while scopolamine (0.025 mg/kg IP) and mecamylamine decreased, mean discrimination index. Zebrafish discriminated different movements (vertical, horizontal, oblique) and the discrimination index increased significantly when moving poorly discriminated shapes were presented, thus increasing visual attention. Taken together these findings demonstrate that VORT is a viable, fast and useful model to evaluate sustained attention in zebrafish and for predicting the efficacy of pharmacotherapies for cognitive disorders. [ABSTRACT FROM AUTHOR]
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- 2014
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143. Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish.
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Braida, Daniela, Ponzoni, Luisa, Martucci, Roberta, Sparatore, Fabio, Gotti, Cecilia, and Sala, Mariaelvina
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ZEBRA danio , *LABORATORY zebrafish , *LEARNING in animals , *ANIMAL intelligence , *ANIMAL memory , *NICOTINIC acetylcholine receptors , *SPATIAL memory , *PSYCHOPHARMACOLOGICAL research - Abstract
Rationale: Neuronal nicotinic acetylcholine receptors (nAChRs) play a modulatory role in cognition, and zebrafish provide a preclinical model to study learning and memory. Objectives: We investigated the effect of nicotine (NIC) and some new cytisine-derived partial agonists (CC4 and CC26) on spatial memory in zebrafish using a rapid assay on T-maze task. The role of α4/α6β2 and the α7 nAChRs in NIC-induced memory enhancement was evaluated using selective nAChR antagonists. Results: Low and high doses of NIC, cytisine (CYT), CC4 and CC26 respectively improved and worsened the mean running time, showing an inverted U dose-response function. The effective dose (ED50) (×10 mg/kg) was 0.4 for CC4, 4.5 for CYT, 140 for NIC and 200 for CC26. NIC-induced cognitive enhancement was reduced by the selective nAChR subtype antagonists: methyllycaconitine (MLA) for α7, α-conotoxin (MII) for α6β2, dihydro-β-erythroidine (DhβE) for α4β2, the nonselective antagonist mecamylamine (MEC) and the muscarinic antagonist scopolamine (SCOP), with DhβE being more active than MLA or MII. All the partial agonists blocked the cognitive enhancement. The improvement with the maximal active dose of each partial agonist was blocked by low doses of DhβE (0.001 mg/kg) and MII (0.01 mg/kg). MLA reduced the effects of CC26 and CC4 at doses of 0.01 and 1 mg/kg, respectively, but did not antagonize CYT-induced memory improvement at any of the tested dose. No change in swimming activity was observed. Conclusions: Our findings demonstrate that zebrafish make a useful model for the rapid screening of the effect of new α4β2 nAChR compounds on spatial memory. [ABSTRACT FROM AUTHOR]
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- 2014
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144. Persistent cognitive and affective alterations at late withdrawal stages after long-term intermittent exposure to tobacco smoke or electronic cigarette vapour: Behavioural changes and their neurochemical correlates
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Daniela Braida, Cecilia Gotti, Lucia Carboni, Mariaelvina Sala, Michele Zoli, Luisa Ponzoni, Paola Viani, Milena Moretti, Francesco Clementi, Ponzoni, Luisa, Braida, Daniela, Carboni, Lucia, Moretti, Milena, Viani, Paola, Clementi, Francesco, Zoli, Michele, Gotti, Cecilia, and Sala, Mariaelvina
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0301 basic medicine ,Male ,medicine.medical_specialty ,Elevated plus maze ,Crf receptor ,AMPA glutamate receptor ,AMPA glutamate receptors ,AMPA receptor ,Hippocampal formation ,Hippocampus ,Tobacco smoke ,Cigarette Smoking ,Marble burying ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neurochemical ,Cognition ,e-cigarette vapour ,Internal medicine ,medicine ,Animals ,Behaviour ,Maze Learning ,Crf receptors ,Pharmacology ,Inhalation Exposure ,Mice, Inbred BALB C ,Cigarette smoke ,Crf ,NMDA ,Withdrawal ,business.industry ,Recognition, Psychology ,Substance Withdrawal Syndrome ,Affect ,030104 developmental biology ,Endocrinology ,E-Cigarette Vapor ,030220 oncology & carcinogenesis ,NMDA receptor ,Anxiety ,Tobacco Smoke Pollution ,medicine.symptom ,business - Abstract
Smoking cessation induces a withdrawal syndrome associated with anxiety, depression, and impaired neurocognitive functions, but much less is known about the withdrawal of e-cigarettes (e-CIG). We investigated in Balb/c mice the behavioural and neurochemical effects of withdrawal for up to 90 days after seven weeks' intermittent exposure to e-CIG vapour or cigarette smoke (CIG). The withdrawal of e-CIG and CIG induced early behavioural alterations such as spatial memory deficits (spatial object recognition task), increased anxiety (elevated plus maze test) and compulsive-like behaviour (marble burying test) that persisted for 60-90 days. Notably, attention-related (virtual object recognition task) and depression-like behaviours (tail suspension and sucrose preference tests) appeared only 15-30 days after withdrawal and persisted for as long as up to 90 days. At hippocampal level, the withdrawal-induced changes in the levels of AMPA receptor GluA1 and GluA2/3 subunits, PSD 95 protein, corticotropin-releasing factor (Crf) and Crf receptor 1 (CrfR1) mRNA were biphasic: AMPA receptor subunit and PSD95 protein levels initially remained unchanged and decreased after 60-90 days, whereas Crf/CrfR1 mRNA levels initially increased and then markedly decreased after 60 days. These late reductions correlated with the behavioural impairments, particularly the appearance of depression-like behaviours. Our findings show that major behavioural and neurochemical alterations persist or even first appear late after the withdrawal of chronic CIG smoke or e-CIG vapour exposure, and underline importance of conducting similar studies of humans, including e-CIG vapers.
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- 2020
145. Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals.
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Ponzoni, Luisa, Melzi, Gloria, Marabini, Laura, Martini, Andrea, Petrillo, Giulia, Teh, Muy-Teck, Torres-Perez, Jose V., Morara, Stefano, Gotti, Cecilia, Braida, Daniela, Brennan, Caroline H., and Sala, Mariaelvina
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NICOTINE , *ZEBRA danio , *BEHAVIORAL assessment , *TYROSINE hydroxylase , *NICOTINIC receptors , *MEDICAL research - Abstract
Nicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking. We evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal. Zebrafish were exposed to 1 mg/L nicotine for 2 weeks. Dependence was determined using behavioural analysis following mecamylamine-induced withdrawal, and brain nicotinic receptor binding studies. Separate groups of nicotine-exposed and control fish were assessed for anxiety-like behaviours, anhedonia and memory deficits following 2–60 days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60 days after the last drug exposure. Tyrosine hydroxylase (TH) immunoreactivity in pretectum was also analysed. Mecamylamine-precipitated withdrawal nicotine-exposed fish showed increased anxiety-like behaviour as evidenced by increased freezing and decreased exploration. 3H-Epibatidine labeled heteromeric nicotinic acethylcholine receptors (nAChR) significantly increased after 2 weeks of nicotine exposure while 125I-αBungarotoxin labeled homomeric nAChR remained unchanged. Spontaneous nicotine withdrawal elicited anxiety-like behaviour (increased bottom dwelling), reduced motivation in terms of no preference for the enriched side in a place preference test starting from Day 7 after withdrawal and a progressive decrease of memory attention (lowering discrimination index). Behavioural differences were associated with brain gene expression changes: nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60 days, and of htr2a from 7 to 60 days.The expression of c-Fos was significantly increased at 7 days. Finally, Tyrosine hydroxylase (TH) immunoreactivity increased in dorsal parvocellular pretectal nucleus, but not in periventricular nucleus of posterior tuberculum nor in optic tectum, at 60 days after withdrawal. Our findings show that nicotine withdrawal induced anxiety-like behaviour, cognitive alterations, gene expression changes and increase in pretectal TH expression, similar to those observed in humans and rodent models. • Mecamylamine-precipitated withdrawal increases freezing and decreased exploration. • H-Epibatidine labeled nAChR significantly increases after nicotine exposure. • Anxiety, reduced motivation, decreased memory attention is shown after withdrawal. • mRNA expression of chrnα7 and htr2A receptors decreases while that of c-Fos increases. • TH fluorescence intensity increases in dorsal parvocellular pretectal nucleus. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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146. 5-HT1A receptors are involved in the anxiolytic effect of Δ9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague–Dawley rats
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Braida, Daniela, Limonta, Valeria, Malabarba, Lorenzo, Zani, Alessia, and Sala, Mariaelvina
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CANNABINOIDS , *CELL receptors , *CHLORIDES , *RATS , *AMIDES - Abstract
Abstract: The mechanism mediating the effects of cannabinoids on anxiety-related responses appear to involve cannabinoid CB1 and non-CB1 receptors. However, other neurotransmitters may play a role in such effect. This study shows evidence of an interaction between endocannabinoid system and serotonin (5-HT), 1A receptor subtype on anxiety-like behavior in Sprague–Dawley rats. The exogenous cannabinoid agonist, Δ9-tetrahydrocannabinol (THC), and N-(4-hydroxyphenyl)-arachidonylamide, the anandamide transporter inhibitor (AM 404) were evaluated in the elevated plus maze test. THC (0.075–0.75 mg/kg i.p.), given 30 min and AM 404 (0.75–1.25 mg/kg i. p.), given 60 min before the test, exhibited a dose–response anxiolytic effect evaluated in terms of increase in the percentage of total entries and time spent in the open and decrease of total entries and time spent in the closed arms. The anxiolytic effect obtained with the maximal active dose of both THC (0.75 mg/kg) and AM 404 (1.25 mg/kg) was blocked by the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide dihydro chloride (WAY-100635 (300 μg/kg, s.c.), given 30 min before THC or 15 min before AM 404. The combination of an ineffective dose of THC (0.015 mg/kg) or AM 404 (0.015 mg/kg) on anxiety-related responses with an ineffective dose of the 5HT1A receptor agonist, 8-Hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (7.5 μg/kg, i.p.), led to a synergistic effect. No interference with spontaneous motor activity, evaluated in an activity cage for 5 min, in rats given the drugs alone or in combination, was found. These data suggest that the anxiolytic effect produced by endo- and eso-cannabinoids is modulated by 5-HT1A receptors. [Copyright &y& Elsevier]
- Published
- 2007
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147. Δ9-Tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats
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Braida, Daniela, Iosuè, Stefania, Pegorini, Simona, and Sala, Mariaelvina
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MURIDAE , *CANNABINOIDS , *ANIMAL experimentation , *DRUGS of abuse - Abstract
Abstract: On the basis of contradictory findings on the rewarding effects of Δ9-tetrahydrocannabinol (Δ9-THC) in laboratory animals, the effect of the compound on conditioned place preference and intracerebroventricular (i.c.v.) self-administration in a free-choice procedure, using a wide range of doses (0.015–6 mg/kg for conditioned place preference test and 0.01–1 μg/2 μl/infusion for i.c.v. self-administration), was studied in Wistar rats. The present results showed that Δ9-THC induced reward in both tests, but only at the lowest tested doses (0.075–0.75 mg/kg i.p. for conditioned place preference test and 0.01–0.02 μg/infusion for i.c.v. self-administration). This effect was fully antagonised by i.p. pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4 methyl pyrazole 3-carboxamide] (0.25–1 mg/kg), and the opiate receptor antagonist, naloxone (0.5–2 mg/kg), suggesting the involvement of both endocannabinoid and opioid systems. In conclusion, these findings demonstrate, for the first time, that low doses of Δ9-THC can act as an effective reinforcer in Wistar rats providing a reliable animal model of human marijuana abuse. [Copyright &y& Elsevier]
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- 2004
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148. eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures
- Author
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Michael M. Poe, Luisa Ponzoni, Luca Murru, Flavia Valtorta, Elham Taha, Chiara Verpelli, Angela Bachi, Carlo Sala, Mariaelvina Sala, Maura Francolini, Kobi Rosenblum, Iliana Barrera, Jonathan Zapata, James M. Cook, Christopher Heise, Adele Mossa, Maksym V. Kopanitsa, Elena Vezzoli, Fabrizia C. Guarnieri, Maria Passafaro, Roberta Benfante, Christopher G. Proud, Giulio Ippolito, Francesco Rusconi, Michael Rajesh Stephen, Angela Cattaneo, Alexey G. Ryazanov, Caterina Montani, Daniela Braida, Heise, Christopher, Taha, Elham, Murru, Luca, Ponzoni, Luisa, Cattaneo, Angela, Guarnieri, Fabrizia C, Montani, Caterina, Mossa, Adele, Vezzoli, Elena, Ippolito, Giulio, Zapata, Jonathan, Barrera, Iliana, Ryazanov, Alexey G, Cook, Jame, Poe, Michael, Stephen, Michael Rajesh, Kopanitsa, Maksym, Benfante, Roberta, Rusconi, Francesco, Braida, Daniela, Francolini, Maura, Proud, Christopher G, Valtorta, Flavia, Passafaro, Maria, Sala, Mariaelvina, Bachi, Angela, Verpelli, Chiara, Rosenblum, Kobi, and Sala, Carlo
- Subjects
0301 basic medicine ,Elongation Factor 2 Kinase ,Cognitive Neuroscience ,Neural Inhibition ,Biology ,Neurotransmission ,EEF2 ,Inhibitory postsynaptic potential ,Hippocampus ,Synaptic Transmission ,gamma-Aminobutyric acid ,Conditioning (Psychology) ,inhibitory synapse ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Epilepsy ,0302 clinical medicine ,GABA receptor ,Conditioning, Psychological ,medicine ,Animals ,translation elongation regulation ,Cells, Cultured ,gamma-Aminobutyric Acid ,Cerebral Cortex ,Mice, Knockout ,Neurons ,hippocampu ,Animal ,GABAA receptor ,Synapsin ,Original Articles ,Fear ,Neuron ,medicine.disease ,Receptors, GABA-A ,Synapsins ,fear conditioning ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy.
- Published
- 2016
149. Impaired approach to novelty and striatal alterations in the oxytocin receptor deficient mouse model of autism.
- Author
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Leonzino, Marianna, Ponzoni, Luisa, Braida, Daniela, Gigliucci, Valentina, Busnelli, Marta, Ceresini, Ilaria, Duque-Wilckens, Natalia, Nishimori, Katsuhiko, Trainor, Brian C., Sala, Mariaelvina, and Chini, Bice
- Subjects
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OXYTOCIN receptors , *AUTISM spectrum disorders , *AUTISM , *COGNITIVE testing , *DOPAMINERGIC neurons - Abstract
Long-standing studies established a role for the oxytocin system in social behavior, social reward, pair bonding and affiliation. Oxytocin receptors, implicated in pathological conditions affecting the social sphere such as autism spectrum disorders, can also modulate cognitive processes, an aspect generally overlooked. Here we examined the effect of acute (pharmacological) or genetic (Oxtr −/−) inactivation of oxytocin receptor-mediated signaling, in male mice, in several cognitive tests. In the novel object recognition test, both oxytocin receptor antagonist treated wild type animals and Oxtr −/− mice lacked the typical preference for novelty. Oxtr −/− mice even preferred the familiar object; moreover, their performance in the Morris water maze did not differ from wild types, suggesting that oxytocin receptor inactivation did not disrupt learning. Because the preference for novel objects could be rescued in Oxtr −/− mice with longer habituation periods, we propose that the loss of novelty preferences following Oxtr inactivation is due to altered processing of novel contextual information. Finally, we observed an increased expression of excitatory synaptic markers in the striatum of Oxtr −/− mice and a greater arborization and higher number of spines/neuron in the dorsolateral area of this structure, which drives habit formation. Our data also indicate a specific reshaping of dorsolateral striatal spines in Oxtr −/− mice after exposure to a novel environment, which might subtend their altered approach to novelty, and support previous work pointing at this structure as an important substrate for autistic behaviors. • Inactivation of the oxytocin receptors impairs mice interest for novel objects. • Novelty preference is rescued by habituation to the environment. • Dorsolateral striatum is a key region for oxytocin-regulated approach to novelty. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
150. Corrigendum to “Δ9-Tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats” [Eur. J. Pharmacol. 506 (2005) 63–69]
- Author
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Braida, Daniela, Iosuè, Stefania, Pegorini, Simona, and Sala, Mariaelvina
- Published
- 2005
- Full Text
- View/download PDF
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