Carla Perrone-Capano

University of Naples Federico II | UNINA · Department of Pharmacy

In the brain microRNAs (miRNAs) are believed to play a role in orchestrating synaptic plasticity at a higher-level by acting as an additional mechanism of translational regulation, alongside the mRNAs/polysome system. Despite extensive research, our understanding of the specific contribution of individual miRNA to the function of dopaminergic neuro...

Structural, functional, and molecular alterations in excitatory spines are a common hallmark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure and composition of...

Structural, functional, and molecular alterations in excitatory spine synapses are a common hallmark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure and composi...

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for...

In a million years, under the pressure of natural selection, hominins have acquired the abilities for vocal learning, music, and language. Music is a relevant human activity, highly effective in enhancing sociality, is a universal experience common to all known human cultures, although it varies in rhythmic and melodic complexity. It has been part...

Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by social deficits, repetitive stereotyped behaviors, and altered inflammatory responses. Accordingly, children with ASD show decreased plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation, which is the endog...

Dorsal root ganglia (DRG) neurons synthesize acetylcholine (ACh), in addition to their peptidergic nature. They also release ACh and are cholinoceptive, as they express cholinergic receptors. During gangliogenesis, ACh plays an important role in neuronal differentiation, modulating neuritic outgrowth and neurospecific gene expression. Starting from...

To form and maintain extremely intricate and functional neural circuitry, mammalian neurons are typically endowed with highly arborized dendrites and a long axon. The synapses that link neurons to neurons or to other cells are numerous and often too remote for the cell body to make and deliver new proteins to the right place in time. Moreover, syna...

The cytoskeleton and its associated proteins present at the plasma membrane not only determine the cell shape but also modulate important aspects of cell physiology such as intracellular transport including secretory and endocytic pathways. Continuous remodeling of the cell structure and intense communication with extracellular environment heavily...

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people’s lif...

The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic inflammation by the blood...

The relatively few dopaminergic neurons in the mammalian brain are mostly located in the midbrain and regulate many important neural functions, including motor integration, cognition, emotive behaviors and reward. Therefore, alteration of their function or degeneration leads to severe neurological and neuropsychiatric diseases. Unraveling the mecha...

[This corrects the article DOI: 10.1371/journal.pone.0030661.].

While protein synthesis in neurons is largely attributed to cell body and dendrites, the capability of synaptic regions to synthesize new proteins independently of the cell body has been widely demonstrated as an advantageous mechanism subserving synaptic plasticity. Thus, the contribution that local protein synthesis at synapses makes to physiolog...

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology have advanced considerably in recent years. A wealth of data show that 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunctio...

With contributors from the anatomy, cell biology, molecular genetics, cognitive sciences, neuroscience, and pharmacology departments of universities and research laboratories around the world, this volume contains 11 chapters addressing specification and patterning of the rostral neural tube; inductive factors and their receptors in the specificati...

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfu...

miRNAs are master regulators of gene expression in diverse biological processes, including the modulation of neuronal cytoarchitecture. The identification of their physiological target genes remains one of the outstanding challenges. Recently, it has been demonstrated that the activation of serotonin receptor 7 (5-HT7R) plays a key role in regulati...

Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central ner...

Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, t...

The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated micro...

Dendritic spines, small protrusions emerging from the dendrites of most excitatory synapses in the mammalian brain, are highly dynamic structures and their shape and number is continuously modulated by memory formation and other adaptive changes of the brain. In this study, using a behavioral paradigm of motor learning, we applied the non-linear an...

Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here, we report that prolonged activation of the serotonin 5‐ HT 7 receptor (5‐ HT 7R) with selective agon...

Music is a universal language, present in all human societies. It pervades the lives of most human beings and can recall memories and feelings of the past, can exert positive effects on our mood, can be strongly evocative and ignite intense emotions, and can establish or strengthen social bonds. In this review, we summarize the research and recent...

The 5-HT7 serotonin receptor is revealing a promising target for innovative therapeutic strategies of neurodevelopmental and neuropsychiatric disorders. Here, we report the synthesis of thirty long-chain arylpiperazine analogs of the selective and brain penetrant 5-HT7 receptor agonist LP-211 (1) designed to enhance stability towards microsomal oxi...

Mecp2 null mice model Rett syndrome (RTT) a human neurological disorder affecting females after apparent normal pre- and peri-natal developmental periods. Neuroanatomical studies in cerebral cortex of RTT mouse models revealed delayed maturation of neuronal morphology and autonomous as well as non-cell autonomous reduction in dendritic complexity o...

The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signali...

Spine motility analysis has become the mainstay for investigating synaptic plasticity but is limited in its versatility requiring complex, non automatized instrumentations. We describe an entropy-based method for determining the spatial distribution of dendritic spines that allows successful estimation of spine motility from still images. This meth...

Recent studies have indicated that the serotonin receptor subtype 7 (5-HT7R) plays a crucial role in shaping neuronal morphology during embryonic and early postnatal life. Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippoca...

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous an...

At the Nobel lecture for physiology in 1906, Ramón y Cajal famously stated that "the nerve elements possess reciprocal relationships in contiguity but not in continuity," summing up the neuron doctrine. Sixty years later, by the time the central dogma of molecular biology formulated the axis of genetic information flow from DNA to mRNA, and then to...

Brain serotonin (5-HT) systems modulate emotional, motivational and cognitive processes. Mutations in the serotonin transporter (SERT) gene have been associated with susceptibility towards the development of several psychiatric disorders, both in humans and animal models. Present approach exploited a bilateral intra-hippocampus stereotaxic inoculat...

During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS) regionalization, generation of neural precursors (NPs) and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB) has been ass...

Nurr1 and TH expression in in NP lines with stable expression of Nurr1. NP lines were selected for stable expression of Nurr1 as described in Materials and Methods. A and B. real-time PCR of Nurr1 (A) and TH mRNA (B) on differentiated cells in control conditions after Nurr1 overexpression, HPRT was used as normalizing gene. C. Percentage of beta-II...

Research on stem cells has developed as one of the most promising areas of neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was indisputably accepted, eliciting great research efforts. Neural stem cells in the adult mammalian brain are located in the "neurogenic" areas of the subventricular and subgranular zones. Neverth...

Neuronal avalanches, measured in vitro and in vivo, exhibit a robust critical behaviour. Their temporal organization hides the presence of correlations. Here we present experimental measurements of the waiting time distribution between successive avalanches in the rat cortex in vitro. This exhibits a non-monotonic behaviour, not usually found in ot...

Due to their correlation with major human neurological diseases, dopaminergic neurons are some of the most studied neuronal subtypes. Mesencephalic dopaminergic (mDA) differentiation requires the activation of a cascade of transcription factors, among which play a crucial role the nuclear receptor Nurr1 and the paired-like homeodomain 3, Pitx3. Dur...

Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hypera...

Dysfunction of brain dopamine transporter (DAT) has been associated with sensation seeking and impulse-control disorders. We recently generated a new animal model by stereotaxical inoculation of lentiviral vectors, which allowed localized intra-accumbal delivery of modulators for DAT gene: GFP (green fluorescent protein) control, silencers (Sil), a...

Summary of the PCR validations of the microarray results:The Nr4a2, Th, and Egr1 gene expression have been tested by PCR and statistically validated as described in materials and methods. (0.04 MB TIF)

Genes significant in the three analyses with a DAVID annotation. Fields: DAVIDID: DAVID unique ID; EG: Entrez Gene ID; logFC_EG: logarithmic fold change (MesPC-MesE11) based on the EG re-annotation; P.Value_EG: p-value based on the EG re-annotation; adj.P.Val_EG: adjusted (Benjamini-Hochberg) p-value based on the EG re-annotation; ENSID: Ensembl ge...

Functional analysis of the genes significantly over-expressed in MesPC. Each stack represents a group of related functional terms. Each term within each stack is in a row of the table. The number of genes annotated, the percent of representation of the term, and the enrichment p-value are shown. (0.29 MB XLS)

Summary of the Genomatix ModelInspector analysis for V$NEUR-V$NR2F. Rattus norvegicus promoter sequences showing the V$NEUR-V$NR2F module. For each match, the sequence annotation, the position of the module, and the strand are indicated. Over-represented Geneontology terms are also shown starting from page 57. (0.35 MB PDF)

Functional analysis of the genes significantly over-expressed in MesE11. Each stack represents a group of related functional terms. Each term within each stack is in a row of the table. The number of genes annotated, the percent of representation of the term, and the enrichment p-value are shown. (0.19 MB XLS)

Summary of the Genomatix ModelInspector analysis for V$EGR-V$SP1F. Rattus norvegicus promoter sequences showing the V$EGR-V$SP1F module. For each match, the sequence annotation, the position of the module, and the strand are indicated. Over-represented Geneontology terms are also shown starting from page 53. (0.39 MB PDF)

Methylphenidate (MPH) administration to adolescent rodents produces persistent region-specific changes in brain reward circuits and alterations of reward-based behavior. We show that these modifications include a marked increment of serotonin (5-hydroxy-tryptamine) receptor type 7 (Htr7) expression and synaptic contacts, mainly in the nucleus accum...

In the mammalian central nervous system (CNS) an important contingent of dopaminergic neurons are localized in the substantia nigra and in the ventral tegmental area of the ventral midbrain. They constitute an anatomically and functionally heterogeneous group of cells involved in a variety of regulatory mechanisms, from locomotion to emotional/moti...

Affymetrix GeneChip represents a very reliable and standardized technology for genome-wide gene expression screening. However, in experiments carried out on complex biological samples (e.g. brain tissues composed of several diverse cell types), significant noise can arise due to important transcripts being expressed in a relatively small number of...

Midbrain dopaminergic neurons comprise a small group of cells that regulate important functions in the mammalian brain. Their degeneration or dysfunction is involved in many common neurological disorders such as Parkinson’s disease, depression, schizophrenia, attention deficit hyperactive disorder and drug addiction. Here we review recent studies t...

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of a very high connectivity degree. Here we discuss a recent model based on self-organized critical...

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of a very high connectivity degree. Here we study a recent model based on self-organized criticalit...

The glial cell line-derived neurotrophic factor (GDNF) exerts trophic actions on a number of cell types, including mesencephalic dopaminergic (mDA) neurons. Using rat mesencephalic primary cultures enriched in mDA neurons, we show that protracted GDNF stimulation increases their survival and neurite outgrowth. It modulates the expression of genes e...

The transcription factor Nurr1 is essential for the generation of midbrain dopaminergic neurons (mDA). Only a few Nurr1-regulated genes have so far been identified and it remains unclear how Nurr1 influences the development and function of dopaminergic neurons. To identify novel Nurr1 target genes we have used genome-wide expression profiling in ra...

Chronic cocaine use leads to pronounced alterations in neuronal functions in brain circuits associated with reward. In the present study, we examined in the rat midbrain the effects of acute, subchronic (5 days) and chronic cocaine treatments (14 days) on the gene expression of transcription factors involved in the development and maintenance of do...

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of very high connectivity degree. Here we study a recent model based on self-organized criticality,...

Administration of methylphenidate (MPH, Ritalin) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-re...

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treat...

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model that is based on self-organized criticality and takes into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists of an electrical network with threshol...

To identify genes potentially involved in remodelling synaptic connections, we induced the temporary detachment of pre- and post-synaptic elements by axotomy or denervation of rat superior cervical ganglion neurons. cDNA microarray analysis followed by stringent selection criteria allowed the identification of a panel of genes whose expression was...

Administration of methylphenidate (MPH, Ritalin®) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-r...

Most brain models focus on associative memory or calculation capability, experimentally inaccessible using physiological methods. Here we present a model explaining a basic feature of electroencephalograms (EEG). Our model is based on an electrical network with threshold firing and plasticity of synapses that reproduces very robustly the measured e...

The transcription factor/nuclear receptor Nurr1 is essential for the differentiation of midbrain dopaminergic neurones. Here we demonstrate that, during the ontogeny of rat ventral mesencephalon, nurr1 gene expression is developmentally regulated and its levels show a sharp peak between embryonic day E13 and E15, when most dopaminergic neurones dif...

We analyzed the molecular mechanisms involved in the acquisition and maturation of dopaminergic (DA) neurons generated in vitro from rat ventral mesencephalon (MES) cells in the presence of mitogens or specific signaling molecules. The addition of basic fibroblast growth factor (bFGF) to MES cells in serum-free medium stimulates the proliferation o...

To understand the onset and the molecular mechanisms triggering dopaminergic (DA) dysregulation in Attention-Deficit Hyperactivity Disorder (ADHD), we have used the Spontaneously Hypertensive Rats (SHR), the most widely studied animal model for this disease. We have studied the pattern of expression of specific genes involved in DA neuron different...

The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dicta...