A5031642285- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Genetics and Neurodevelopmental Disorders
- Neural dynamics and brain function
- Functional Brain Connectivity Studies
- Pluripotent Stem Cells Research
- Amino Acid Enzymes and Metabolism
- RNA and protein synthesis mechanisms
- Epilepsy research and treatment
- Stress Responses and Cortisol
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Autism Spectrum Disorder Research
- Nuclear Receptors and Signaling
- Neuroendocrine regulation and behavior
- Genomics and Chromatin Dynamics
- Adenosine and Purinergic Signaling
- RNA regulation and disease
- Advanced Neuroimaging Techniques and Applications
- Hypothalamic control of reproductive hormones
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- Genetic Neurodegenerative Diseases
University of Pisa
2012-2024
University of Florence
2007
Fondazione Stella Maris
2007
University of Bologna
2007
University of Messina
2007
Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, it remains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by drugs (DREADD)-based chemogenetics magnetic resonance imaging (fMRI), an approach we term "chemo-fMRI," to causally probe the brain-wide substrates modulated describe generation of a conditional knockin...
Serotonin (5-HT)-synthetizing neurons, which are confined in the raphe nuclei of rhombencephalon, provide a pervasive innervation central nervous system (CNS) and involved modulation plethora functions both developing adult brain. Classical studies have described post-natal development serotonergic axons as linear process terminal field innervation. However, technical limitations hampered fine morphological characterization. With advent genetic mouse models, possibility to label specific...
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits stereotyped behaviours. Recent psychosocial neuroimaging studies have highlighted reward-processing reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological molecular determinants of these remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about origin neurophysiological...
The endogenous NMDA receptor (NMDAR) agonist d -aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing adulthood. It well established that postnatal reduction of cerebral levels due to concomitant onset oxidase (DDO) activity, a flavoenzyme selectively degrades bicarboxylic -amino acids. In present work, we show content mouse decreases after birth, whereas Ddo mRNA concomitantly increase. Interestingly,...
Research Article14 December 2018Open Access Source DataTransparent process RGS9-2 rescues dopamine D2 receptor levels and signaling in DYT1 dystonia mouse models Paola Bonsi Corresponding Author [email protected] orcid.org/0000-0001-5940-9028 Laboratory of Neurophysiology Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy Search for more papers by this author Giulia Ponterio Department Systems Medicine, University Tor Vergata, Valentina Vanni Annalisa Tassone Giuseppe Sciamanna Sara...
Genomic mechanisms enhancing risk in males may contribute to sex bias autism. The ubiquitin protein ligase E3A gene ( Ube3a ) affects cellular homeostasis via control of turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage duplication or triplication chromosomal region 15q11-13 causes 1 2% autistic cases. Here, we test the hypothesis that increased dosage influence autism-relevant phenotypes a sex-biased manner. We show mice extra copies exhibit...
Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates fine-tuning of neuron development and establishment wiring patterns in brain. However, whether is involved maintenance neuronal circuitry adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess impact depletion during adulthood on serotonergic system organization. Data show density fibers increased hippocampus decreased thalamic paraventricular nucleus (PVN) as...
Neurons producing serotonin (5-hydroxytryptamine, 5-HT) constitute one of the most widely distributed neuronal networks in mammalian central nervous system (CNS) and exhibit a profuse innervation throughout CNS already at early stages development. Serotonergic neuron specification is controlled by combination secreted molecules transcription factors such as Shh, Fgf4/8, Nkx2.2, Lmx1b Pet1. In mouse, Pet1 mRNA expression appears between 10 11 days post coitum (dpc) serotonergic post-mitotic...
Abstract Mechanisms of gender-specific synaptic plasticity in the striatum, a brain region that controls motor, cognitive and psychiatric functions, remain unclear. Here we report Rhes, GTPase enriched medium spiny neurons (MSNs) alters striatal cAMP/PKA signaling cascade manner. While Rhes knockout (KO) male mice, compared to wild-type (WT) had significant basal increase pathway, KO females exhibited much stronger response this selectively under conditions dopamine/adenosine-related drug...
Abnormal hippocampal neural plasticity has been implicated in behavioural abnormalities and complex neuropsychiatric conditions, including bipolar disorder (BD). However, the determinants of this alteration remain unknown. This work tests hypothesis that neurotransmitter serotonin (5-HT) is a key determinant neuroplasticity, its absence leads to maladaptive behaviour relevant for BD. Depletion brain 5-HT Tph2 mutant mice resulted reduced despair, anxiety, marked aggression lower habituation...
Serotonin-releasing fibers depart from the raphe nuclei to profusely innervate entire central nervous system, displaying in some brain regions high structural plasticity response genetically induced abrogation of serotonin synthesis. Chronic fluoxetine treatment used as a tool model peri-physiological, clinically relevant elevation is also able cause rearrangements serotonergic innervating hippocampus. Whether this effect limited hippocampal-innervating or extends other populations axons not...
Physiology and behavior are structured temporally to anticipate daily cycles of light dark, ensuring fitness survival. Neuromodulatory systems in the brain—including those involving serotonin dopamine—exhibit oscillations neural activity help shape circadian rhythms. Disrupted neuromodulation can cause abnormalities that thought underlie several neuropsychiatric disorders, including bipolar mania schizophrenia, for which a mechanistic understanding is still lacking. Here, we show genetically...
Serotonin has been gaining increasing attention during the last two decades due to dual function of this monoamine as key regulator critical developmental events and neurotransmitter. Importantly, unbalanced serotonergic levels temporal phases might contribute onset neuropsychiatric disorders, such schizophrenia autism. Despite evidences from both animal models human genetic studies have underpinned importance serotonin homeostasis maintenance central nervous system development adulthood,...
Abstract The D-aspartate oxidase ( DDO ) gene encodes the enzyme responsible for catabolism of D-aspartate, an atypical amino acid enriched in mammalian brain and acting as endogenous NMDA receptor agonist. Considering key role receptors neurodevelopmental disorders, recent findings suggest a link between dysmetabolism schizophrenia. To clarify on development functioning, we used mouse model with constitutive Ddo overexpression depletion. In these mice, found reduced number BrdU-positive...
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of spinal motor neurons as well corticospinal (CSN) large pyramidal within cortex layer V. An intense microglia immune response has been associated with both upper and lower neuron in ALS patients, whereas microgliosis occurrence hSOD1G93A mice—the best model this disease—is not clear remains under debate. Since impact cells neuronal environment seems to be crucial for initiation progression disease, here we...
ABSTRACT Background Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of deletion on number dopamine neurons, (3) nigrostriatal‐sensitive behavior during aging knockout mice. Methods Radioactive situ hybridization was assessed adult The beam‐walking test executed 3‐, 6‐ and 12‐month‐old Immunohistochemistry midbrain tyrosine hydroxylase (TH)–positive neurons performed Results is expressed TH‐positive SNpc ventral tegmental area. Moreover, lack leads...
Subcortical band heterotopia (SBH, or double cortex syndrome) is a neuronal migration disorder consisting of heterotopic bands gray matter located between the and ventricular surface, with without concomitant pachygyria. Most cases show diffuse anteriorly predominant (A>P) abnormality. All familial 53% to 84% sporadic A>P SBH harbor mutation DCX gene, leaving genetic causes unexplained, counseling problematic, in remaining patients. Our purpose was verify extent which exonic deletions...
PCDH19 epilepsy (DEE9) is an X-linked syndrome associated with cognitive and behavioral disturbances. Since heterozygous females are affected, while mutant males spared, it likely that DEE9 pathogenesis related to disturbed cell-to-cell communication mosaicism. However, the effects of mosaic expression on cortical networks unknown. We mimicked pathology by introducing a patch protein in one hemisphere cortex conditional knockout mice day after birth. In contralateral area, was unaffected,...
In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well large aspiny cholinergic interneurons, where it thought to modulate dopamine-dependent signaling. Consistent with this knowledge, considering that dopaminergic neurotransmission altered neurological psychiatric disorders, here we sought investigate whether mRNA expression brain regions of patients Parkinson's disease (PD),...
Abstract Previous evidence pointed out a role for the striatal-enriched protein Rhes in modulating dopaminergic transmission. Based on knowledge that cocaine induces both addiction and motor stimulation, through its ability to enhance signaling corpus striatum, we have now explored involvement of effects associated with this psychostimulant. Our behavioral data showed lack knockout animals caused profound alterations stimulation following exposure, eliciting significant leftward shift...
Modeling biological systems in vitro has contributed to clarification of complex mechanisms simplified and controlled experimental conditions. Mouse embryonic stem (mES) cells can be successfully differentiated toward specific neuronal cell fates, thus representing an attractive tool dissect, vitro, that underlie features. In this study, we generated characterized a reporter mES line, called Tph2GFP, which the vital GFP replaces tryptophan hydroxylase 2 (Tph2) gene. Tph2GFP selectively...