Antonietta Bernardo

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Verified

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• PhD
• Senior Researcher at Istituto Superiore di Sanità

Demyelinating diseases are a group of pathologies characterized by the alteration of myelin—that is, the coating that wraps around most of the nerve fibres of the central and peripheral nervous system, whose goal is the improvement of nerve conduction and the preservation of energy spent during action potential propagation [...]

Retina can receive incidental γ-ray exposure from various sources. For example, although radiation therapy is a crucial tool for managing head and neck tumors, patients may develop ocular complications as collateral damage from accidental irradiation. Recently, there has been concern that retinal irradiation during space flight may compromise missi...

Biofilm at water-oil interface of hypoxic water columns of microcosms, prepared from a lacustrine sample, that used diesel as a carbon source was found to show electrogenic properties. These microcosms named, liquid microbial fuel cells (L-MFCs) were electrically characterized using a custom electronic analyzer; accurate determination of voltage (V...

Niemann Pick type C disease (NPC) is a rare disorder characterized by lysosomal lipid accumulation that damages peripheral organs and the central nervous system. Currently, only miglustat is authorized for NPC treatment in Europe, and thus the identification of new therapies is necessary. The hypothesis addressed in this study is that increasing ad...

Our previous studies have demonstrated that specific peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists play a fundamental role in oligodendrocyte progenitor (OP) differentiation, protecting them against oxidative and inflammatory damage. The antihypertensive drug Telmisartan (TLM) was shown to act as a PPAR-γ modulator. This study inve...

Niemann–Pick type C (NPC) disease is a wide-spectrum clinical condition classified as a neurovisceral disorder affecting mainly the liver and the brain. It is caused by mutations in one of two genes, NPC1 and NPC2, coding for proteins located in the lysosomes. NPC proteins are deputed to transport cholesterol within lysosomes or between late endoso...

Curcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions....

The oil-water interface formed during an oil spill represents a challenging environment for pelagic communities living in aquatic ecosystems. At this anoxic barrier, we report the formation of a microbial hydrocarbonoclastic biofilm capable of electron transfer along the water column. This biofilm generated a membrane of surface-active compounds th...

The oil-water interface formed during an oil spill represents a challenging environment for pelagic communities living in aquatic ecosystems. At this anoxic barrier, we report the formation of a microbial hydrocarbonoclastic biofilm capable of electron transfer along the water column. This biofilm generated a membrane of surface-active compounds th...

An adequate protection from oxidative and inflammatory reactions, together with the promotion of oligodendrocyte progenitor (OP) differentiation, is needed to recover from myelin damage in demyelinating diseases. Mitochondria are targets of inflammatory and oxidative insults and are essential in oligodendrocyte differentiation. It is known that nuc...

Niemann Pick type C (NPC) disease is a rare neurovisceral disorder. Mutations in npc1 gene induce an intracellular accumulation of unesterified cholesterol in the endosomal/lysosomal system causing cell death. We recently showed that stimulation of adenosine A2A receptors (A2AR) restores cholesterol accumulation in late endosomes/lysosomes in human...

Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-...

Mutations in the MLC1 gene, which encodes a protein expressed in brain astrocytes, are the leading cause of MLC, a rare leukodystrophy characterized by macrocephaly, brain edema, subcortical cysts, myelin and astrocyte vacuolation. Although recent studies indicate that MLC1 protein is implicated in the regulation of cell volume changes, the exact r...

The activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is known to exert anti-inflammatory and neuroprotective effects and PPAR-γ agonists are considered potential therapeutic agents in brain diseases including those affecting myelin. In demyelinating diseases such as multiple sclerosis (MS), inflammation is on...

Microglial activation is a dynamic process, central to neuroinflammation, which can have beneficial or pathogenic effects to human health. Mitochondria are key players in neuroinflammatory and neurodegenerative processes, common to most brain diseases. To further our knowledge on the role of mitochondria in the modulation of neuroinflammation, we f...

Phytoprostanes (PhytoPs) are formed in higher plants from α-linolenic acid via a non-enzymatic free radical catalyzed pathway and act as endogenous mediators capable of protecting cells from damage under various conditions related to oxidative stress. Humans are exposed to PhytoPs as they are present in relevant quantities in vegetable food and pol...

Niemann-Pick type C1 (NPC1) disease is a rare neurovisceral disorder characterized by intracellular accumulation of unesterified cholesterol, sphingolipids, and other lipids in the lysosomal compartment. A deregulation of lysosomal calcium has been identified as one of the earliest steps of the degenerative process. Since adenosine A2A receptors (A...

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the most studied nuclear receptor since its identification as a target to treat metabolic and neurological diseases. Besides exerting anti-inflammatory and neuroprotective effects, PPAR-γ agonists, such as the insulin-sensitizing drug pioglitazone, promote the differentiation...

Huntington disease (HD) is a neurodegenerative disease caused by expansion of CAG repeats in the huntingtin (Htt) gene. The expression of hMTH1, the human hydrolase that degrades oxidized purine nucleoside triphosphates, grants protection in a chemical HD mouse model in which HD-like features are induced by the mitochondrial toxin 3-nitropropionic...

Acetylcholine (ACh) is a major neurotransmitter but also an important signaling molecule in neuron-glia interactions. Expression of ACh receptors has been reported in several glial cell populations, including oligodendrocytes (OLs). Nonetheless, the characterization of muscarinic receptors in these cells, as well as the description of the cholinerg...

The complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical...

We have previously shown that natural (15-deoxy-Δ-prostaglandin J2) and synthetic (pioglitazone) agonists of peroxisome proliferator-activated receptor γ (PPAR-γ) strengthen the intrinsic cellular mechanisms protecting oligodendrocyte (OL) progenitors (OPs) from oxidative insults and promote their differentiation. Here, we demonstrate that repeated...

hNGF activation of TrkA and p75 NTR and their associated intracellular signaling pathways. The cartoon illustrates in a schematic manner the activation of TrkA and p75NTR by hNGF and the main downstream signaling pathways. As shown, the signaling streams leading to pain or to survival and growth/differentiation involve largely distinct signaling mo...

Expression of NGF receptors TrkA, P75NTR and sortilin in hippocampal neurons. Western blot and densitometric analysis of (A) pTrkA (Y490) (B) p75NTR and (C) sortilin in cell extracts from hippocampal cells after 3 and 5 days of culture compared to PC12 cells. Hippocampal cells were stimulated with 4 nM NGF. (TIF)

Details of in vitro phosphorylation assays. (DOC)

Details of in vitro survival, proliferation and neurotrophic assays (DOC)

Concentration of hNGFR100 mutants necessary to achieve half-maximum (50%) TF1 cell proliferation (dose range 5–50,000 pg/ml) (DOC)

Primary and tertiary structural comparison. 3D structural and sequence comparisons between the crystal structure of the Fab rat αD11 and the crystal structures of human or humanized antibodies, Fabs, IgGs or of their complexes with antigens indentified in the PDB database (release #101, July 2002). The plotted variables are: The skeleton Cα r.m.s.d...

Time course of dose-dependent nociceptive response triggered by hNGF muteins. (A) 1 µg/mouse; (B) 2 µg/mouse and (C) 4 µg/mouse. At all doses and time points hNGFR100E does not induce pain. Points are the mean of the percentage derived from the ratio between ipsilateral vs controlateral measures ± s.e.m. (TIF)

List of NGF from different species and muteins derived from hNGF (DOC)

Summary of the derived kinetic and equilibrium binding constants of hproNGF and hNGF and their muteins in position 100 towards TrkA and p75 receptors (DOC)

During adulthood, the neurotrophin Nerve Growth Factor (NGF) sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, H...

The term NSAID refers to structurally diverse chemical compounds that share the ability to inhibit the activity of the prostaglandin (PG) biosynthetic enzymes, the cyclooxygenase (COX) isoforms 1 and 2. The suppression of PG synthesis at sites of inflammation has been regarded as primarily responsible for the beneficial properties of NSAIDs, but se...

ACh and its receptors are expressed at early stages of nervous system development suggesting that it may have alternative roles during neurogenesis, independent on its synaptic function as neurotransmitter. ACh receptors have been also found in several glial cells such as astrocytes, oligodendrocytes and Schwann cells suggesting a role for ACh in t...

Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists may control brain inflammation and, therefore, may be useful for the treatment of human CNS inflammatory conditions. The PPAR-gamma agonists delay the onset and ameliorate clinical manifestations in animal demyelinating disease models, in w...

The peroxisome proliferator-activated receptor γ (PPARγ) is a member of a large group of nuclear receptors controlling lipid and glucose metabolism, energy homeostasis, adipose cell and macrophage differentiation. We have recently shown that PPARγ is constitutively expressed in rat primary microglial cultures and is down regulated during microglial...

The last decade has witnessed an increasing interest for the role played by the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in controlling inflammation in peripheral organs as well as in the brain. Activation of PPAR-gamma has been shown to control the response of microglial cells, the main macrophage population found in brain par...

Cyclooxygenase-2 (COX-2) and presenilin (PSEN) 1 and 2 genes are regulated during development as well as in pathological conditions associated to hypoxia. In this study, we investigated their patterns of expression during the first 2 weeks of postnatal life in a rat model of moderate global perinatal asphyxia that we have previously reported to be...

In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty ac...

The nitric oxide-releasing derivative of flurbiprofen, NCX 2216, has a safer gastrointestinal profile than the parent drug flurbiprofen and a strong anti-amyloidogenic activity. Here, we show that in primary microglial cultures, in addition to the expected inhibition of prostaglandin synthesis, NCX 2216 specifically activated the peroxisome prolife...

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a large group of nuclear receptors controlling reproduction, metabolism, development and immune response. Upon activation by specific agonists, these receptors form dimers and translocate to the nucleus, where they act as agonist-dependent transcription factors and regulat...

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is constitutively expressed in primary cultures of rat microglia, the main population of brain resident macrophages, and its ligand-dependent activation leads to the repression of several microglial functions. A few non-steroidal anti-inflammatory drugs (NSAIDs), e.g. indomethacin an...

We have previously reported that rat primary microglial cultures express the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and that several functions associated with the activation of these cells, including nitric oxide (NO) and tumor necrosis factor-alpha synthesis, are down-regulated by 15-deoxy-delta12,14-prostag...

To understand the basis of oligodendrocyte (OL) susceptibility to oxidative injury, purified rat OL cultures at different stages of maturation were exposed to nitric oxide (NO) donors with fast or slow kinetics of release and to tert-butyl-hydroperoxide, a membrane-permeant organic hydroperoxide. OL precursors (pre-OL) displayed the highest vulnera...

The importance of peroxisomes in central nervous system (CNS) comes from the observation that in several peroxisomal disorders, such as Zellweger syndrome, Adrenoleukodystrophy, Rhizomelyc chondrodysplasia punctata etc, severe neurological impairments were observed. They have been involved in several physiological processes in brain, such as protec...

TNFalpha has been implicated in several demyelinating disorders, including multiple sclerosis (MS) and X-adrenoleukodystrophy (X-ALD). TNFalpha abundance is greatly increased in the areas surrounding damaged regions of the central nervous system of patients with MS and X-ALD, but its role in the observed demyelination remains to be elucidated. A cl...

The original article to which this Erratum refers was published in GLIA (2003)41:3–14

A characteristic feature of neuritic plaques in Alzheimer's disease is represented by the presence of activated astrocytes, surrounding dystrophic neurons and beta-amyloid deposition. To explore the role of astrocytes in in vitro beta-amyloid neurotoxicity, we studied the effect of beta-amyloid treatment in hippocampal neurons in two different cell...

We have extended our previous findings and shown that human immunodeficiency virus Tat protein, in addition to nitric oxide (NO), stimulated rat microglial cultures to release pro-inflammatory cytokine interleukin-1beta and tumour necrosis factor-alpha in a nuclear factor (NF)-kappaB-dependent manner. At the same time, Tat stimulated the accumulati...

Astrocytes are the most versatile cells of the neural tissue. Numerous astrocytic functions—such as protection from oxidative damage, catabolism of neuroactive D-amino acids acting as neuromodulators, synthesis and catabolism of some lipid molecules, and, possibly, gluconeogenesis—reside in peroxisomes. The expression of several peroxisomal enzymes...

A common theory for the pathogenesis of Alzheimer's disease is that neuronal death is mediated by free radicals 1. In this disease, neuronal degeneration occurs in brain regions involved in learning and memory such as the hippocampus 2. Using hippocampal slices of Wistar rats superfused in oxygenated artificial cerebro-spinal fluid (aCSF) in vitro,...

Astrocytosis is a common feature of amyloid plaques, the hallmark of Alzheimer's disease (AD), along with activated microglia, neurofibrillary tangles, and β-amyloid (βA) deposition. However, the relationship between astrocytosis and neurodegeneration remains unclear. To assess whether βA-stimulated astrocytes can damage neurons and contribute to β...

Isoprostanes are a family of biologically active molecules recently characterized, which is emerging as a new class of specific and reliable markers of in vivo and ex vivo lipid peroxidation and oxidative damage. These molecules are stable, relatively abundant and easily detectable by sensitive and specific analytical methods. In the last years, th...

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of a large group of nuclear receptors controlling the proliferation of peroxisomes that is involved in the downregulation of macrophage functions. Here, we report that PPAR-gamma was constitutively expressed in rat primary microglial cultures and that such expression was...

We investigated the effect of the peroxisomal proliferator (PP) perfluorodecanoic acid (PFDA), alone or in combination with 9-cis-retinoic acid (RX) on the human glioblastoma cell line Lipari (LI). Cell proliferation, apoptotic rate, peroxisome morphology and morphometry, peroxisomal enzyme activities and the presence of peroxisome proliferator-act...

Most normal and neoplastic cell types are resistant to tumor necrosis factor (TNF) cytotoxicity unless cotreated with protein or RNA synthesis inhibitors, such as cycloheximide and actinomycin D. Cellular resistance to TNF requires TNF receptor-associated factor 2 (TRAF2), which has been hypothesized to act mainly by mediating activation of the tra...

In order to understand the molecular basis of the synergistic action of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor...

Abstract In order to understand the molecular basis of the synergistic action of interferon  (IFN‐) and tumour necrosis factor α (TNF‐α) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor 1 (IRF...

The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using highly purified cultures of rat OL, we report that gp120 binds to OL and induces functional alterations in these cells. Indeed, the percentage of cells expressing myelin basic protein (MBP) and the levels of all...

1. We have previously shown that acute exposure to the HIV coat protein gp120 interferes with the -adrenergic regulation of astroglial and microglial cells (Leviet al., 1993). In particular, exposure to 100 pM gp120 for 30 min depressed the phosphorylation of vimentin and glial fibrillary acidic protein (GFAP) induced by isoproterenol in rat cortic...

The goal of our study was to assess whether the human immunodeficiency virus (HIV) coat protein gp120 induces functional alterations in astrocytes and microglia, known for their reactivity and involvement in most types of brain pathology. We hypothesized that gp120-induced anomalies in glial functions, if present, might be mediated by changes in th...

Insulin function in the nervous system is still poorly understood. Possible roles as a neuromodulator and as a growth factor have been proposed (Baskin et al. , 1987, Ann. Rev. Physiol. 49, 335–347). Stable cell lines may provide an appropriate experimental system for the analysis of insulin action on the various cellular components of the central...

Morphological and morphometric parameters (volume density (Vv), numerical density (NA) and mean diameter (D)) of newborn liver peroxisomes were measured throughout the first week of life in rats born to mothers treated with clofibrate (ethyl 2 p-chlorophenoxy isobutyrate) during the last five days of pregnancy. In control studies the same analyses...