Giorgia Tosoni - Profile on Academia.edu (original) (raw)

Papers by Giorgia Tosoni

Research paper thumbnail of Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a ... more The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases.

Research paper thumbnail of Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Current Opinion in Pharmacology

Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiolog... more Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiology and development beyond the gastrointestinal tract, including the modulation of brain development. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Pattern recognition receptors of the innate immune system that recognize microbial products, such as peptidoglycans have emerged as potential key regulators of gut microbiome-brain interactions. Peptidoglycan-sensing molecules are expressed in the placenta and brain during specific time windows of development. Moreover, peptidoglycans are ubiquitously present in circulation and can cross the blood brain barrier. This review brings together the current evidence supporting a broad function of peptidoglycans well beyond host's immunity, extending to neurodevelopment and behavior.

Research paper thumbnail of Unbiased profiling of miR‐132 targetome with implications in adult hippocampal neurogenesis and Alzheimer’s disease

Unbiased profiling of miR‐132 targetome with implications in adult hippocampal neurogenesis and Alzheimer’s disease

Alzheimer's & Dementia, 2021

MicroRNA‐132 (miR‐132), a potent neuroimmune regulator, is robustly downregulated in the brain of... more MicroRNA‐132 (miR‐132), a potent neuroimmune regulator, is robustly downregulated in the brain of Alzheimer’s Disease (AD) patients and its deficiency has been functionally linked to amyloid deposition, TAU hyperphosphorylation and memory decline, in both human and rodents. Of note, miR‐132 can explain a higher percentage of the observed variance in histopathological AD phenotypes than APOE e4, a major risk factor for AD. This suggests that miR‐132‐dependent network‐based gene regulation in human AD brain converges onto biological pathways that can drive disease endophenotypes. miR‐132 regulates several targets in molecular pathways involved in AD pathophysiology, such as memory formation, neuronal morphogenesis, synaptic plasticity, immune homeostasis, neuronal survival and cell death. Recently, we reported miR‐132 as a potent regulator of adult hippocampal neurogenesis (AHN) in healthy and AD brain. Direct miR‐132 infusion in the AD mouse brain can counteract several aspects of pa...

Research paper thumbnail of Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease

Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease

Cell Stem Cell

Research paper thumbnail of Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Current Opinion in Pharmacology

Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiolog... more Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiology and development beyond the gastrointestinal tract, including the modulation of brain development. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Pattern recognition receptors of the innate immune system that recognize microbial products, such as peptidoglycans have emerged as potential key regulators of gut microbiome-brain interactions. Peptidoglycan-sensing molecules are expressed in the placenta and brain during specific time windows of development. Moreover, peptidoglycans are ubiquitously present in circulation and can cross the blood brain barrier. This review brings together the current evidence supporting a broad function of peptidoglycans well beyond host's immunity, extending to neurodevelopment and behavior.

Research paper thumbnail of Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a ... more The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases.

Research paper thumbnail of Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Current Opinion in Pharmacology

Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiolog... more Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiology and development beyond the gastrointestinal tract, including the modulation of brain development. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Pattern recognition receptors of the innate immune system that recognize microbial products, such as peptidoglycans have emerged as potential key regulators of gut microbiome-brain interactions. Peptidoglycan-sensing molecules are expressed in the placenta and brain during specific time windows of development. Moreover, peptidoglycans are ubiquitously present in circulation and can cross the blood brain barrier. This review brings together the current evidence supporting a broad function of peptidoglycans well beyond host's immunity, extending to neurodevelopment and behavior.

Research paper thumbnail of Unbiased profiling of miR‐132 targetome with implications in adult hippocampal neurogenesis and Alzheimer’s disease

Unbiased profiling of miR‐132 targetome with implications in adult hippocampal neurogenesis and Alzheimer’s disease

Alzheimer's & Dementia, 2021

MicroRNA‐132 (miR‐132), a potent neuroimmune regulator, is robustly downregulated in the brain of... more MicroRNA‐132 (miR‐132), a potent neuroimmune regulator, is robustly downregulated in the brain of Alzheimer’s Disease (AD) patients and its deficiency has been functionally linked to amyloid deposition, TAU hyperphosphorylation and memory decline, in both human and rodents. Of note, miR‐132 can explain a higher percentage of the observed variance in histopathological AD phenotypes than APOE e4, a major risk factor for AD. This suggests that miR‐132‐dependent network‐based gene regulation in human AD brain converges onto biological pathways that can drive disease endophenotypes. miR‐132 regulates several targets in molecular pathways involved in AD pathophysiology, such as memory formation, neuronal morphogenesis, synaptic plasticity, immune homeostasis, neuronal survival and cell death. Recently, we reported miR‐132 as a potent regulator of adult hippocampal neurogenesis (AHN) in healthy and AD brain. Direct miR‐132 infusion in the AD mouse brain can counteract several aspects of pa...

Research paper thumbnail of Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease

Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease

Cell Stem Cell

Research paper thumbnail of Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Bacterial peptidoglycans as novel signaling molecules from microbiota to brain

Current Opinion in Pharmacology

Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiolog... more Mounting evidence indicates that gut microbiota exerts a broad range of effects on host physiology and development beyond the gastrointestinal tract, including the modulation of brain development. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Pattern recognition receptors of the innate immune system that recognize microbial products, such as peptidoglycans have emerged as potential key regulators of gut microbiome-brain interactions. Peptidoglycan-sensing molecules are expressed in the placenta and brain during specific time windows of development. Moreover, peptidoglycans are ubiquitously present in circulation and can cross the blood brain barrier. This review brings together the current evidence supporting a broad function of peptidoglycans well beyond host's immunity, extending to neurodevelopment and behavior.