Publications by authors named "Enrica Boda"
Article Synopsis
- Brain size and neural cell diversity depend on how multipotent neural progenitor cells (NPCs) grow and specialize, with mistakes in this process causing hereditary microcephaly (MCPH), which leads to smaller brain sizes and intellectual disabilities.
- Research identified specific genetic variants related to MCPH, but the exact role of CIT protein activity in brain development was unclear, prompting the creation of mouse models for study.
- Findings revealed that while the mouse models didn't mimic human microcephaly, they did show signs of cell damage and abnormalities; human organoids created from the models exhibited loss of structural complexity and issues with cell division, highlighting the importance of CIT functions in human brain development.
Article Synopsis
- In response to trauma or neurodegenerative diseases, adult OPCs activate, migrate, and attempt to proliferate to repair damaged areas, but their effectiveness is hindered by a glial scar formed by reactive astrocytes and microglia.
- The review highlights the importance of focusing on OPC behavior in the context of glial scars and proposes therapeutic strategies that could enhance OPC differentiation and promote remyelination in the CNS.
Article Synopsis
- Synaptic abnormalities are a key feature in various neurological disorders, and understanding their causes is essential for developing treatments.
- Rett syndrome (RTT) is a rare disorder primarily affecting girls and is linked to mutations in a gene that impacts synaptic connectivity.
- Recent findings emphasize the role of astrocytes (supportive brain cells) in RTT, showing that those lacking a specific protein release harmful substances that disrupt synapse formation, with elevated IL-6 levels contributing to these effects.
Article Synopsis
- * Developmental differences among these OPCs impact their reactions to damage or stress as adults, particularly when exposed to DNA-damaging agents like cisplatin.
- * The study reveals that dorsal and ventral OPCs respond differently to injury due to their unique origins and varied activation of protective mechanisms, making them differently susceptible to issues arising from DNA damage.
Article Synopsis
- The Elongase of Very-Long Fatty Acid 5 (Elovl5) gene produces an enzyme crucial for elongating long-chain fatty acids, particularly omega-3 and omega-6 fatty acids, which are vital for producing polyunsaturated fatty acids (PUFAs).
- Mutations in this gene lead to spino-cerebellar ataxia type 38 (SCA38), a rare neurological disease characterized by issues like abnormal gait and speech difficulties, and has been studied using a mouse model lacking this gene.
- The study investigates the expression of Elovl5 in different neural cell types and brain regions, revealing it is expressed in notable areas like the cerebellum and hippocampus, and
Article Synopsis
- * The study found that knocking out the MAPK isoform JNK1 significantly reduces myelin in the cerebral cortex and corpus callosum during postnatal and adult stages, leading to higher OPC density and proliferation early in life.
- * JNK1 knockout OPCs have smaller territories and simpler structures, and although differentiation seems normal, both knockout and treated OLs have reduced surface area, highlighting JNK1's crucial role in OPC function and myelination.
Article Synopsis
- Epidemiological studies indicate a significant link between air pollution, especially particulate matter (PM), and an increased incidence of Multiple Sclerosis (MS), leading to more hospital admissions and relapses.
- PM exposure affects the immune system and creates an oxidative-inflammatory response while also impacting processes like myelin repair in the central nervous system (CNS).
- Research shows that in a mouse model simulating demyelination, exposure to fine PM after injury negatively affects myelin regeneration and increases the activity of glial cells, suggesting PM may worsen demyelinating diseases by impeding the CNS's healing abilities.
Article Synopsis
- MicroRNAs, specifically miR-125a-3p, have been found to significantly influence the development of glial cells, particularly oligodendrocytes, which are crucial for nerve cell support and myelination.
- Inactive lesions of multiple sclerosis (MS) patients show increased levels of miR-125a-3p, suggesting a link between this microRNA and the disease's progression, as its regulation impacts oligodendrocyte precursor cells (OPCs).
- Experiments indicate that high levels of miR-125a-3p hinder OPC maturation, while lowering its expression can speed up the remyelination process, highlighting potential therapeutic targets for improving recovery in demyelinating diseases.
Article Synopsis
- Cerebral cavernous malformation (CCM) is a genetic cerebrovascular disorder affecting the central nervous system, with a prevalence of 0.3-0.5% in the general population, caused by mutations in three specific genes.
- Mutations in these genes alone are not enough to cause the disease; additional factors like oxidative stress and inflammation play a significant role in its development.
- The study reveals that loss of the KRIT1 gene in fibroblasts leads to increased production of inflammatory and angiogenic factors, which influence the behavior of nearby endothelial cells, highlighting a new way KRIT1 mutations contribute to CCM.
Exposure to air pollution - and particularly to particulate matter (PM) - is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis.
View Article and Find Full Text PDFDepressive disorders are complex, multifactorial disorders that have been traditionally attributed exclusively to neuronal abnormalities. However, recent studies have increased our understanding of the contribution of glial cells-and particularly of oligodendroglia-to the pathogenesis and treatment outcome of depression and stress-related disorders. This review scrutinizes recent studies focusing on the neurosupportive functions exerted by myelin and oligodendrocyte lineage cells and their disruption in depression and stress-related disorders.
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- *Silencing KRIT1 in various human endothelial cells increased pro-inflammatory adhesion molecules and apoptosis, indicating a connection to endothelial dysfunction.
- *Mice with heterozygous KRIT1 mutations showed increased expression of inflammatory markers and greater fat accumulation in atherosclerosis-prone areas when subjected to a high-fructose diet, highlighting KRIT1's role in vascular disease.
Heparan sulfate proteoglycans (HSPGs) critically modulate adhesion-, growth-, and migration-related processes. Here, we show that the transmembrane protein, Nogo-A, inhibits neurite outgrowth and cell spreading in neurons and Nogo-A-responsive cell lines via HSPGs. The extracellular, active 180 amino acid Nogo-A region, named Nogo-A-Δ20, binds to heparin and brain-derived heparan sulfate glycosaminoglycans (GAGs) but not to the closely related chondroitin sulfate GAGs.
View Article and Find Full Text PDFEmerging pharmacological approaches to promote neurogenesis from endogenous glial cells.
Biochem Pharmacol
October 2017
Article Synopsis
- * Recent research highlights the potential of using glial cells in the brain, which can either initiate new neuron growth or be converted into neurons under certain conditions.
- * This review focuses on advancements in understanding how glial cells can be harnessed for neurogenesis, including the exploration of drugs and small molecules that can enhance this process.
Article Synopsis
- Treatment options for degenerative cerebellar ataxias are limited, with a focus on hereditary forms that allow for early diagnosis and possible preventive treatments before symptoms appear.
- The study compared two preventive strategies: cell replacement therapy using healthy Purkinje cells and motor training to enhance survival and function.
- Results showed that while grafted Purkinje cells had good survival rates, they did not improve ataxic symptoms, whereas motor training positively impacted Purkinje cell survival and slightly improved motor function in the tbl mouse model.
Article Synopsis
- Fingolimod (FTY720) is related to sphingosine and shows neuroprotective effects in models of Alzheimer's disease, particularly against the toxicity of amyloid-beta (Aβ).
- Research indicates that FTY720 rapidly increases the presence of neuroprotective NMDARs in neurons while relocating harmful NMDARs to synapses, which helps reduce neuron sensitivity to toxic Aβ.
- The protective mechanism of FTY720 operates through Sphingosine-1-phosphate receptors, and its ability to move NMDARs may improve cognitive performance in Alzheimer's mouse models after treatment.
The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response.
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- Oligodendrocyte progenitor cells (OPCs) in the adult central nervous system are crucial for generating new oligodendrocytes throughout life and avoid exhaustion through asymmetric cell division.
- A study revealed that dividing OPCs produce sister cells with varying characteristics and behaviors, indicating a mix in cell fates that occurs right after cell division.
- This variation is influenced by both intrinsic factors and external conditions, such as increased activity or injury, which affect how OPCs behave and evolve from division to function.
NG2-expressing parenchymal precursors (NG2+p) serve as primary source of myelinating oligodendrocytes in both the developing and adult Central Nervous System (CNS). However, their abundance, limited differentiation potential at adult stages along with stereotypic reaction to injury independent of the extent of myelin loss suggest that NG2+p exert functions additional to myelin production. In support of this view, NG2+p express a complex battery of molecules known to exert neuromodulatory and neuroprotective functions.
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- An enriched environment can enhance cognitive performance in Alzheimer's disease patients and animal models, indicating its potential therapeutic benefits.
- In a study with APP(Swe)/PS1(L166P) mice, early exposure to an enriched environment improved spatial memory but temporarily accelerated amyloid plaque formation.
- The research suggests that early life experiences influence plaque dynamics and cognitive health through increased neuronal activity, as suppressing electrical signaling reduced plaque numbers without affecting intracellular amyloids.
Article Synopsis
- * Nogo-A and its receptor NgR1 are expressed differently in this system; Nogo-A labels immature neuroblasts, while NgR1 marks germinal astrocytes, indicating their roles in neurogenesis regulation.
- * Experimental results show that the interaction between Nogo-66 and NgR1 inhibits the proliferation of stem cells and that Nogo-A enhances neuroblast migration toward the OB via the Rho/ROCK pathway, independent of NgR1. *
In Alzheimer's disease (AD), the severity of cognitive symptoms is better correlated with the levels of soluble amyloid-beta (Aβ) rather than with the deposition of fibrillar Aβ in amyloid plaques. In APP/PS1 mice, a murine model of AD, at 8 months of age the cerebellum is devoid of fibrillar Aβ, but dosage of soluble Aβ(1-42), the form which is more prone to aggregation, showed higher levels in this structure than in the forebrain. Aim of this study was to investigate the alterations of intrinsic membrane properties and of synaptic inputs in Purkinje cells (PCs) of the cerebellum, where only soluble Aβ is present.
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- - NG2-expressing cells are cycling precursors that can mature into oligodendrocytes, exhibiting different properties that suggest they are at various maturation stages.
- - The GPR17 receptor is identified as an important marker during oligodendrocyte development, changing its expression and localization as these cells transition from precursors to premyelinating stages.
- - GPR17 does not play a role in the initial response of NG2-expressing cells to brain injury, but its expression increases in the postacute phase, indicating a specific function in the reactivity of these cells after injury.