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Papers by Antonella Borreca

Research paper thumbnail of Loss of Interleukin 1 Signaling in Microglia Causes Mtor Enhancement and Impairment of Microglia-Mediated Synapse Elimination

IBRO Neuroscience Reports

Research paper thumbnail of Epigenetic Mechanism Affects Microglia Status and Synaptic Pruning Mechanism in Fragile X Syndrome

IBRO Neuroscience Reports

Research paper thumbnail of The Key Role of the Amygdala in Stress

InTech eBooks, Jul 5, 2017

Research paper thumbnail of Maternal immune activation leads to defective brain blood vessels and intracerebral hemorrhages in male offspring

The EMBO Journal, May 15, 2023

Research paper thumbnail of Maternal immune activation leads to defective brain–blood vessels and intracerebral hemorrhages in male offspring

Research paper thumbnail of Ribosomal RACK1 Regulates the Dendritic Arborization by Repressing FMRP Activity

International Journal of Molecular Sciences

FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its ... more FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational machinery to regulate the translation of its mRNA targets is not yet fully understood. Here, we show that FMRP localizes on translational machinery by interacting with the ribosomal binding protein, Receptor for Activated C Kinase 1 (RACK1). The binding of FMRP to RACK1 removes the translational repressive activity of FMRP and promotes the translation of PSD-95 mRNA, one specific target of FMRP. This binding also results in a reduction in the level of FMRP phosphorylation. We also find that the morphological abnormalities induced by Fmr1 siRNA in cortical neurons are rescued by the overexpression of a mutant form of RACK1 that cannot bind ribosomes. Thus, these results provide a new m...

Research paper thumbnail of Spatacsin mutations in autosomal recessive juvenile ALS

Research paper thumbnail of AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy

Molecular Neurobiology, 2018

Research paper thumbnail of Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer’s disease and other tauopathies

Research paper thumbnail of eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts

Journal of Experimental & Clinical Cancer Research, 2016

Research paper thumbnail of SMN affects membrane remodelling and anchoring of the protein synthesis machinery

Journal of cell science, Jan 7, 2016

Disconnection between membrane signalling and actin networks may have catastrophic effects depend... more Disconnection between membrane signalling and actin networks may have catastrophic effects depending on cell size and polarity. The Survival Motor Neuron (SMN) protein is ubiquitously involved in assembly of spliceosomal small nuclear ribonucleoprotein particles. Other SMN functions could, however, affect cellular activities driving asymmetrical cell surface expansions. Genes able to mitigate SMN deficiency operate within pathways as part of which SMN can act: mRNA translation, actin network, and endocytosis. Here, we found that SMN accumulates at membrane protrusions during dynamic rearrangement of the actin filament. In addition to localization data, we show that SMN interacts with caveolin-1, which mediates anchoring of translation machinery components. Importantly, SMN deficiency depletes the plasma membrane of ribosomes, and this correlates with the failure of fibroblasts to extend membrane protrusions. These findings strongly support a relationship between SMN and membrane dyn...

Research paper thumbnail of NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease

Human molecular genetics, Jan 15, 2015

Disarrangement in functions and quality control of mitochondria at synapses are early events in A... more Disarrangement in functions and quality control of mitochondria at synapses are early events in Alzheimer's disease (AD) pathobiology. We reported that a 20-22 kDa NH2-tau fragment mapping between 26 and 230 amino acids of the longest human tau isoform (aka NH2htau): (i) is detectable in cellular and animal AD models, as well in synaptic mitochondria and cerebrospinal fluids (CSF) from human AD subjects; (ii) is neurotoxic in primary hippocampal neurons; (iii) compromises the mitochondrial biology both directly, by inhibiting the ANT-1-dependent ADP/ATP exchange, and indirectly, by impairing their selective autophagic clearance (mitophagy). Here, we show that the extensive Parkin-dependent turnover of mitochondria occurring in NH2htau-expressing post-mitotic neurons plays a pro-death role and that UCHL-1, the cytosolic Ubiquitin-C-terminal hydrolase L1 which directs the physiological remodeling of synapses by controlling ubiquitin homeostasis, critically contributes to mitochond...

Research paper thumbnail of Indistinguishable pattern of amygdala and hippocampus rewiring following tone or contextual fear conditioning in C57BL/6 mice

Frontiers in Behavioral Neuroscience, 2013

Research paper thumbnail of Reactivating fear memory under propranolol resets pre-trauma levels of dendritic spines in basolateral amygdala but not dorsal hippocampus neurons

Front. Behav. Neurosci., 2013

Research paper thumbnail of The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning

Nature Communications, 2017

The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational co... more The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95. Of note, BC1 KO mice show aberrant structural plasticity in response to whisker deprivation, impaired texture novel object recognition and altered social behavior. Thus, our study highlights a role for BC1 RNA in experience-dependent plasticity and learning in the mammalian adult neocortex, and provides insight into the function of brain ncRNAs regulating synaptic transmission, plasticity and behavior, with potential relevance in the context of intellectual disabilities and...

Research paper thumbnail of Fmr1-KO mice failure to detect object novelty associates with a post-test decrease of structural and synaptic plasticity upstream of the hippocampus

Scientific Reports

Mice with deletion of the FMR1 gene show episodic memory impairments and exhibit dendritic spines... more Mice with deletion of the FMR1 gene show episodic memory impairments and exhibit dendritic spines and synaptic plasticity defects prevalently identified in non-training conditions. Based on evidence that synaptic changes associated with normal or abnormal memory emerge when mice are cognitively challenged, here we examine whether, and how, fragile entorhinal and hippocampal synapses are remodeled when mice succeed or fail to learn. We trained Fmr1 knockout (KO) and wild-type C57BL/6J (WT) mice in the novel object recognition (NOR) paradigm with 1 h or 24 h training-to-test intervals and then assessed whether varying the time between the presentation of similar and different objects modulates NOR performance and plasticity along the entorhinal cortex-hippocampus axis. At the 1 h-interval, KO mice failed to discriminate the novel object, showed a collapse of spines in the lateral entorhinal cortex (LEC), and of long-term potentiation (LTP) in the lateral perforant path (LPP), but a no...

Research paper thumbnail of Research Article CREB Regulates Experience-Dependent Spine Formation and Enlargement in Mouse Barrel Cortex

Copyright © 2015 Annabella Pignataro et al. This is an open access article distributed under the ... more Copyright © 2015 Annabella Pignataro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Experience modifies synaptic connectivity through processes that involve dendritic spine rearrangements in neuronal circuits. Although cAMP response element binding protein (CREB) has a key function in spines changes, its role in activity-dependent rearrangements in brain regions of rodents interacting with the surrounding environment has received little attention so far. Here we studied the effects of vibrissae trimming, a widely used model of sensory deprivation-induced cortical plasticity, on processes associated with dendritic spine rearrangements in the barrel cortex of a transgenicmousemodel of CREB downregulation (mCREB mice). We found that sensory deprivation through prolonged whisker trimming leads to an increased numbe...

Research paper thumbnail of Identification of a choroid plexus vascular barrier closing during intestinal inflammation

Science

Locking down access to the brain Inflammatory bowel disease is best known for intestinal symptoms... more Locking down access to the brain Inflammatory bowel disease is best known for intestinal symptoms but can also cause a variety of extraintestinal manifestations in other organs. It can also be associated with cognitive and psychiatric effects, including anxiety and depression. Using mouse models of intestinal inflammation, Carloni et al . uncovered a potential pathogenic link between these aspects of inflammatory bowel disease. The inflammatory process causes the gut vascular barrier to become more permeable, resulting in the spread of inflammation beyond the intestine, while the vascular barrier in the choroid plexus shuts down, helping protect the brain from inflammation but also potentially impairing communication between organs and impairing some brain functions. —YN

Research paper thumbnail of FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer's disease: A Losing Game

Frontiers in Molecular Biosciences

Fragile X mental retardation protein (FMRP) is an RNA binding protein (RBP) whose absence is esse... more Fragile X mental retardation protein (FMRP) is an RNA binding protein (RBP) whose absence is essentially associated to Fragile X Syndrome (FXS). As an RNA Binding Protein (RBP), FMRP is able to bind and recognize different RNA structures and the control of specific mRNAs is important for neuronal synaptic plasticity. Perturbations of this pathway have been associated with the autistic spectrum. One of the FMRP partners is the APP mRNA, the main protagonist of Alzheimer’s disease (AD), thereby regulating its protein level and metabolism. Therefore FMRP is associated to two neurodevelopmental and age-related degenerative conditions, respectively FXS and AD. Although these pathologies are characterized by different features, they have been reported to share a number of common molecular and cellular players. The aim of this review is to describe the double-edged sword of FMRP in autism and AD, possibly allowing the elucidation of key shared underlying mechanisms and neuronal circuits. A...

Research paper thumbnail of Adenosine A2A receptor inhibition reduces synaptic and cognitive hippocampal alterations in Fmr1 KO mice

Translational Psychiatry

In fragile X syndrome (FXS) the lack of the fragile X mental retardation protein (FMRP) leads to ... more In fragile X syndrome (FXS) the lack of the fragile X mental retardation protein (FMRP) leads to exacerbated signaling through the metabotropic glutamate receptors 5 (mGlu5Rs). The adenosine A2A receptors (A2ARs), modulators of neuronal damage, could play a role in FXS. A synaptic colocalization and a strong permissive interaction between A2A and mGlu5 receptors in the hippocampus have been previously reported, suggesting that blocking A2ARs might normalize the mGlu5R-mediated effects of FXS. To study the cross-talk between A2A and mGlu5 receptors in the absence of FMRP, we performed extracellular electrophysiology experiments in hippocampal slices of Fmr1 KO mouse. The depression of field excitatory postsynaptic potential (fEPSPs) slope induced by the mGlu5R agonist CHPG was completely blocked by the A2AR antagonist ZM241385 and strongly potentiated by the A2AR agonist CGS21680, suggesting that the functional synergistic coupling between the two receptors could be increased in FXS....

Research paper thumbnail of Loss of Interleukin 1 Signaling in Microglia Causes Mtor Enhancement and Impairment of Microglia-Mediated Synapse Elimination

IBRO Neuroscience Reports

Research paper thumbnail of Epigenetic Mechanism Affects Microglia Status and Synaptic Pruning Mechanism in Fragile X Syndrome

IBRO Neuroscience Reports

Research paper thumbnail of The Key Role of the Amygdala in Stress

InTech eBooks, Jul 5, 2017

Research paper thumbnail of Maternal immune activation leads to defective brain blood vessels and intracerebral hemorrhages in male offspring

The EMBO Journal, May 15, 2023

Research paper thumbnail of Maternal immune activation leads to defective brain–blood vessels and intracerebral hemorrhages in male offspring

Research paper thumbnail of Ribosomal RACK1 Regulates the Dendritic Arborization by Repressing FMRP Activity

International Journal of Molecular Sciences

FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its ... more FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational machinery to regulate the translation of its mRNA targets is not yet fully understood. Here, we show that FMRP localizes on translational machinery by interacting with the ribosomal binding protein, Receptor for Activated C Kinase 1 (RACK1). The binding of FMRP to RACK1 removes the translational repressive activity of FMRP and promotes the translation of PSD-95 mRNA, one specific target of FMRP. This binding also results in a reduction in the level of FMRP phosphorylation. We also find that the morphological abnormalities induced by Fmr1 siRNA in cortical neurons are rescued by the overexpression of a mutant form of RACK1 that cannot bind ribosomes. Thus, these results provide a new m...

Research paper thumbnail of Spatacsin mutations in autosomal recessive juvenile ALS

Research paper thumbnail of AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy

Molecular Neurobiology, 2018

Research paper thumbnail of Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer’s disease and other tauopathies

Research paper thumbnail of eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts

Journal of Experimental & Clinical Cancer Research, 2016

Research paper thumbnail of SMN affects membrane remodelling and anchoring of the protein synthesis machinery

Journal of cell science, Jan 7, 2016

Disconnection between membrane signalling and actin networks may have catastrophic effects depend... more Disconnection between membrane signalling and actin networks may have catastrophic effects depending on cell size and polarity. The Survival Motor Neuron (SMN) protein is ubiquitously involved in assembly of spliceosomal small nuclear ribonucleoprotein particles. Other SMN functions could, however, affect cellular activities driving asymmetrical cell surface expansions. Genes able to mitigate SMN deficiency operate within pathways as part of which SMN can act: mRNA translation, actin network, and endocytosis. Here, we found that SMN accumulates at membrane protrusions during dynamic rearrangement of the actin filament. In addition to localization data, we show that SMN interacts with caveolin-1, which mediates anchoring of translation machinery components. Importantly, SMN deficiency depletes the plasma membrane of ribosomes, and this correlates with the failure of fibroblasts to extend membrane protrusions. These findings strongly support a relationship between SMN and membrane dyn...

Research paper thumbnail of NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease

Human molecular genetics, Jan 15, 2015

Disarrangement in functions and quality control of mitochondria at synapses are early events in A... more Disarrangement in functions and quality control of mitochondria at synapses are early events in Alzheimer's disease (AD) pathobiology. We reported that a 20-22 kDa NH2-tau fragment mapping between 26 and 230 amino acids of the longest human tau isoform (aka NH2htau): (i) is detectable in cellular and animal AD models, as well in synaptic mitochondria and cerebrospinal fluids (CSF) from human AD subjects; (ii) is neurotoxic in primary hippocampal neurons; (iii) compromises the mitochondrial biology both directly, by inhibiting the ANT-1-dependent ADP/ATP exchange, and indirectly, by impairing their selective autophagic clearance (mitophagy). Here, we show that the extensive Parkin-dependent turnover of mitochondria occurring in NH2htau-expressing post-mitotic neurons plays a pro-death role and that UCHL-1, the cytosolic Ubiquitin-C-terminal hydrolase L1 which directs the physiological remodeling of synapses by controlling ubiquitin homeostasis, critically contributes to mitochond...

Research paper thumbnail of Indistinguishable pattern of amygdala and hippocampus rewiring following tone or contextual fear conditioning in C57BL/6 mice

Frontiers in Behavioral Neuroscience, 2013

Research paper thumbnail of Reactivating fear memory under propranolol resets pre-trauma levels of dendritic spines in basolateral amygdala but not dorsal hippocampus neurons

Front. Behav. Neurosci., 2013

Research paper thumbnail of The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning

Nature Communications, 2017

The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational co... more The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95. Of note, BC1 KO mice show aberrant structural plasticity in response to whisker deprivation, impaired texture novel object recognition and altered social behavior. Thus, our study highlights a role for BC1 RNA in experience-dependent plasticity and learning in the mammalian adult neocortex, and provides insight into the function of brain ncRNAs regulating synaptic transmission, plasticity and behavior, with potential relevance in the context of intellectual disabilities and...

Research paper thumbnail of Fmr1-KO mice failure to detect object novelty associates with a post-test decrease of structural and synaptic plasticity upstream of the hippocampus

Scientific Reports

Mice with deletion of the FMR1 gene show episodic memory impairments and exhibit dendritic spines... more Mice with deletion of the FMR1 gene show episodic memory impairments and exhibit dendritic spines and synaptic plasticity defects prevalently identified in non-training conditions. Based on evidence that synaptic changes associated with normal or abnormal memory emerge when mice are cognitively challenged, here we examine whether, and how, fragile entorhinal and hippocampal synapses are remodeled when mice succeed or fail to learn. We trained Fmr1 knockout (KO) and wild-type C57BL/6J (WT) mice in the novel object recognition (NOR) paradigm with 1 h or 24 h training-to-test intervals and then assessed whether varying the time between the presentation of similar and different objects modulates NOR performance and plasticity along the entorhinal cortex-hippocampus axis. At the 1 h-interval, KO mice failed to discriminate the novel object, showed a collapse of spines in the lateral entorhinal cortex (LEC), and of long-term potentiation (LTP) in the lateral perforant path (LPP), but a no...

Research paper thumbnail of Research Article CREB Regulates Experience-Dependent Spine Formation and Enlargement in Mouse Barrel Cortex

Copyright © 2015 Annabella Pignataro et al. This is an open access article distributed under the ... more Copyright © 2015 Annabella Pignataro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Experience modifies synaptic connectivity through processes that involve dendritic spine rearrangements in neuronal circuits. Although cAMP response element binding protein (CREB) has a key function in spines changes, its role in activity-dependent rearrangements in brain regions of rodents interacting with the surrounding environment has received little attention so far. Here we studied the effects of vibrissae trimming, a widely used model of sensory deprivation-induced cortical plasticity, on processes associated with dendritic spine rearrangements in the barrel cortex of a transgenicmousemodel of CREB downregulation (mCREB mice). We found that sensory deprivation through prolonged whisker trimming leads to an increased numbe...

Research paper thumbnail of Identification of a choroid plexus vascular barrier closing during intestinal inflammation

Science

Locking down access to the brain Inflammatory bowel disease is best known for intestinal symptoms... more Locking down access to the brain Inflammatory bowel disease is best known for intestinal symptoms but can also cause a variety of extraintestinal manifestations in other organs. It can also be associated with cognitive and psychiatric effects, including anxiety and depression. Using mouse models of intestinal inflammation, Carloni et al . uncovered a potential pathogenic link between these aspects of inflammatory bowel disease. The inflammatory process causes the gut vascular barrier to become more permeable, resulting in the spread of inflammation beyond the intestine, while the vascular barrier in the choroid plexus shuts down, helping protect the brain from inflammation but also potentially impairing communication between organs and impairing some brain functions. —YN

Research paper thumbnail of FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer's disease: A Losing Game

Frontiers in Molecular Biosciences

Fragile X mental retardation protein (FMRP) is an RNA binding protein (RBP) whose absence is esse... more Fragile X mental retardation protein (FMRP) is an RNA binding protein (RBP) whose absence is essentially associated to Fragile X Syndrome (FXS). As an RNA Binding Protein (RBP), FMRP is able to bind and recognize different RNA structures and the control of specific mRNAs is important for neuronal synaptic plasticity. Perturbations of this pathway have been associated with the autistic spectrum. One of the FMRP partners is the APP mRNA, the main protagonist of Alzheimer’s disease (AD), thereby regulating its protein level and metabolism. Therefore FMRP is associated to two neurodevelopmental and age-related degenerative conditions, respectively FXS and AD. Although these pathologies are characterized by different features, they have been reported to share a number of common molecular and cellular players. The aim of this review is to describe the double-edged sword of FMRP in autism and AD, possibly allowing the elucidation of key shared underlying mechanisms and neuronal circuits. A...

Research paper thumbnail of Adenosine A2A receptor inhibition reduces synaptic and cognitive hippocampal alterations in Fmr1 KO mice

Translational Psychiatry

In fragile X syndrome (FXS) the lack of the fragile X mental retardation protein (FMRP) leads to ... more In fragile X syndrome (FXS) the lack of the fragile X mental retardation protein (FMRP) leads to exacerbated signaling through the metabotropic glutamate receptors 5 (mGlu5Rs). The adenosine A2A receptors (A2ARs), modulators of neuronal damage, could play a role in FXS. A synaptic colocalization and a strong permissive interaction between A2A and mGlu5 receptors in the hippocampus have been previously reported, suggesting that blocking A2ARs might normalize the mGlu5R-mediated effects of FXS. To study the cross-talk between A2A and mGlu5 receptors in the absence of FMRP, we performed extracellular electrophysiology experiments in hippocampal slices of Fmr1 KO mouse. The depression of field excitatory postsynaptic potential (fEPSPs) slope induced by the mGlu5R agonist CHPG was completely blocked by the A2AR antagonist ZM241385 and strongly potentiated by the A2AR agonist CGS21680, suggesting that the functional synergistic coupling between the two receptors could be increased in FXS....