Luigia Cristino

Luigia Cristino
Italian National Research Council | CNR · Institute of Biomolecular Chemistry ICB

PhD

About

113
Publications
21,695
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4,644
Citations
Additional affiliations
January 2008 - May 2020
Italian National Research Council
Position
  • Principal Investigator

Publications

Publications (113)
Article
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Anxiety and stress disorders are often characterized by an inability to extinguish learned fear responses. Orexins/hypocretins are involved in the modulation of aversive memories, and dysregulation of this system may contribute to the aetiology of anxiety disorders characterized by pathological fear. The mechanisms by which orexins regulate fear ar...
Preprint
Background and purpose: Anxiety is often characterized by an inability to extinguish learned fear responses. Orexins/hypocretins are involved in the modulation of aversive memories, and dysregulation of this system may contribute to the aetiology of anxiety disorders characterized by pathological fear. The mechanisms by which orexins regulate fear...
Article
Full-text available
The mammalian brain stores and distinguishes among episodic memories, i.e. memories formed during the personal experience, through a mechanism of pattern separation computed in the hippocampal dentate gyrus. Decision-making for food-related behaviors, such as the choice and intake of food, might be affected in obese subjects by alterations in the r...
Article
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The potential, multifaceted therapeutic profile of cannabidiol (CBD), a major constituent derived from the Cannabis sativa plant, covers a wide range of neurological and psychiatric disorders, ranging from anxiety to pediatric epilepsy and drug addiction. However, the molecular targets responsible for these effects have been only partially identifi...
Article
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Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause....
Article
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Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synth...
Article
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Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on do...
Article
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The 3,5-diiodo-L-thyronine (3,5-T2) is an endogenous metabolite of thyroid hormones, whose administration to rodents fed high-fat diet (HFD) prevents body weight increase and reverts the expression pattern of pro-inflammatory factors associated to HFD. The diet-induced obese (D.I.O.) zebrafish (Danio rerio) has been recently used as an experimental...
Article
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Orexin-A (OX-A) protects the brain against oxidative stress-mediated ischemic injury. Since the endocannabinoid 2-arachidonoylglycerol (2-AG) and cannabinoid type-1 (CB1) receptors were previously shown to mediate some of the effects of OX-A exerted through the orexin-1 receptor (OX-1R), we investigated the involvement of 2-AG in OX-A-induced neuro...
Article
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The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the m...
Article
Traumatic brain injury (TBI) is one of the main cause of death in young people and currently no drugs to treat brain injury exist. Recently, we have reported that mice with mild-TBI with a specific injury in the insula, showed elevated levels of a little investigated N -acyl amino acid, the N -oleoyl-glycine (OlGly). N -acyl-amino acids have recent...
Article
Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from act...
Article
Emerging evidence attributes to orexins/hypocretins (ORs) a protective function in the regulation of cardiovascular responses, heart rate, and hypertension. However, little is known about any direct effect of orexins in the heart function. This is of special relevance considering that cardiovascular diseases, including myocardial infarction and hea...
Article
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In states of intestinal dysbiosis, a perturbation of the normal microbiome composition, the intestinal epithelial barrier (IEB) permeability is increased as a result of the disruption of the epithelial tight junction protein network, in which occludin is mostly affected. The loss of IEB integrity promotes endotoxemia, that is, bacterial lipopolysac...
Article
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In the heterogeneous hub represented by the lateral hypothalamus, neurons containing the orexin/hypocretin peptides play a key role in vigilance state transitions and wakefulness stability, energy homeostasis, and other functions relevant for motivated behaviors. Orexin neurons, which project widely to the neuraxis, are innervated by multiple extra...
Article
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Hypocretins/Orexins neuropeptides are known to regulate numerous physiological functions, such as energy homeostasis, food intake, sleep/wake cycle, arousal and wakefulness, in vertebrates. Previous studies on mice have revealed an intriguing orexins/endocannabinoids (ECs) signaling interaction at both structural and functional levels, with OX-A be...
Article
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The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert antiinflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to u...
Chapter
This chapter attempts to piece together knowledge about new advanced microscopy techniques to study the neuroanatomical distribution of endocannabinoid receptors and enzymes at the level of cellular and subcellular structures and organelles in the brain. Techniques ranging from light to electron microscopy up to the new advanced LBM, PALM, and STOR...
Article
The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesti...
Chapter
In this chapter, the neuroanatomical overlap in the distribution of orexin and endocannabinoid systems, as well as the functional interaction between leptin-driven synaptic rewiring of orexinergic neurons and the orexin receptor-mediated activation of 2-arachidonoylglycerol synthesis, will be presented in the context of their role in the regulation...
Article
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Objectives In the ob/ob mouse model of obesity, chronic absence of leptin causes a significant increase of orexin (OX) production by hypothalamic neurons and excessive food intake. The altered OX level is linked to a dramatic increase of the inhibitory innervation of OX producing neurons (OX neurons) and the over expression of the endocannabinoid 2...
Article
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Purpose of review: Hypertension is one of the most challenging health problems inducing cerebrovascular disease and high percentage of death when associated with diabetes, dyslipidemias, and obesity. Orexin/hypocretin is a peptide expressed by a small number of neurons of the dorsolateral hypothalamus, a brain feeding and autonomic "fight-or-fligh...
Article
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γ-aminobutyric acid (GABA) receptors, responding to GABA positive allosteric modulators, are present in the freshwater polyp Hydra vulgaris (Cnidaria, Hydrozoa), one of the most primitive metazoans to develop a nervous system. We examined the occurrence and distribution of GABAA receptor subunits in Hydra tissues by western blot and immunohistochem...
Article
Orexin 1 (OX-1R) and cannabinoid receptor (CB1R) belong to the superfamily of G-protein-coupled receptors (GPCRs) and are mostly coupled to Gq and Gi/o proteins, respectively. In vitro studies in host cells over-expressing OX-1R and CB1R revealed a functional interaction between these receptors, through either their ability to form heteromers or th...
Article
In the hypothalamic arcuate nucleus (ARC), proopiomelanocortin (POMC) neurons and the POMC-derived peptide α-melanocyte-stimulating hormone (α-MSH) promote satiety. POMC neurons receive orexin-A (OX-A)-expressing inputs and express both OX-A receptor type 1 (OX-1R) and cannabinoid receptor type 1 (CB1R) on the plasma membrane. OX-A is crucial for t...
Article
The endogenous NMDA receptor (NMDAR) agonist D-aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing during adulthood. It is well established that postnatal reduction of cerebral D-aspartate levels is due to the concomitant onset of D-aspartate oxidase (DDO) ac...
Article
Endocannabinoids (eCB) are key regulators of excitatory/inhibitory neurotransmission at cannabinoid-1-receptor (CB1R)-expressing axon terminals. The most abundant eCB in the brain, that is 2-arachidonoylglycerol (2-AG), is hydrolyzed by the enzyme monoacylglycerol lipase (MAGL), whose chronic inhibition in the brain was reported to cause CB1R desen...
Article
Pain perception can become altered in individuals with eating disorders and obesity for reasons that have not been fully elucidated. We show that leptin deficiency in ob/ob mice, or leptin insensitivity in the arcuate nucleus of the hypothalamus in mice with high fat diet (HFD)-induced obesity, are accompanied by elevated orexin-A (OX-A) levels and...
Article
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The adipocyte-derived, anorectic hormone, leptin, was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of ROS levels in arcuate nucleus (ARC) neurons. Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor...
Article
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We have investigated the relevance of d-aspartate oxidase, the only enzyme known to selectively degrade d-aspartate (d-Asp), in modulating glutamatergic system homeostasis. Interestingly, the lack of the Ddo gene, by raising d-Asp content, induces a substantial increase in extracellular glutamate (Glu) levels in Ddo-mutant brains. Consistent with a...
Article
The endocannabinoid system (ECS) is a widespread intercellular signaling system that plays a critical role in energy homeostasis, meant as the precise matching of caloric intake with energy expenditure which normally keeps body weight stable over time. Complex interactions between environmental and neurohormonal systems directly contribute to the b...
Conference Paper
Leptin-deficient ob/ob mice display altered innervation on hypothalamic orexin-expressing neurons (OX-N) in favor of inhibitory inputs. Endocannabinoids (eCBs) produced on-demand from OX-N act on presynaptic cannabinoid receptor type 1 (CB1R), reducing neurotransmitter release. Thus, OX-N of ob/ob mice are disinhibited by eCB-mediated reduction of...
Article
Gold nanoparticles are increasingly being employed in innovative biological applications thanks to their advantages of material- and size-dependent physics and chemical interactions with the cellular systems. On the other hand growing concern has emerged on the toxicity which would render gold-based nanoparticles harmful to cell cultures, animals a...
Article
Excessive consumption of high-energy, palatable food contributes to obesity, which results in the metabolic syndrome, heart disease, type-2 diabetes and death. Current knowledge on the function of the hypothalamus as the brain ‘feeding centre’ recognizes this region as the main regulator of body weight in the central nervous system. Because of thei...
Article
Microtubule turnover in the growing axons is required for directional axonal growth and synapse formation in the developing brain. In this issue of The EMBO Journal, Tortoriello et al (2014) show that the microtubule-binding protein SCG10/stathmin-2 is a specific molecular target for a CB1 receptor-mediated effect of Δ(9)-tetrahydrocannabinol (THC)...
Article
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Despite the precise pathogenesis of atopic dermatitis (AD) is still unknown, an immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, according to the so-called outside-inside-outside model. Mast cells (MCs) are involved in AD both by releasing Th2 pola...
Article
The purinergic system is highly involved in the regulation of microglial physiological processes. In addition to the accepted roles for the P2 X4,7 and P2 Y12 receptors activated by adenosine triphosphate (ATP) and adenosine diphosphate, respectively, recent evidence suggests a role for the adenosine A2A receptor in microglial cytoskeletal rearrang...
Chapter
Silver nanoparticles are one of nontoxic and safe wide-range antibacterial agents to the human body, able to kill most harmful microorganisms. This chapter focuses on the antimicrobial characteristics of a silver/polystyrene nanocomposite system. Silver ions enter in the bacterial cells by diffusing through the cell wall and turn the DNA into a con...
Article
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Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive propert...
Conference Paper
In the ventrolateral periaqueductal gray (vlPAG) activation of excitatory output neurons projecting monosynaptically to OFF cells in the rostral ventromedial medulla (RVM) causes antinociceptive responses via OFF cell stimulation and ON cell inhibition. We previously demonstrated that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) deeply affect...
Data
Full-text available
Primary astrocytomas of grade 3 or 4 according to the classification system of the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among adults and are almost invariably fatal despite the use of multimodal therapy. Here we show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural precursor ce...
Article
Full-text available
Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changes on endocannabinoid and cannabinoid receptor type 1 (CB1)-mediated modulation of synapt...
Article
Full-text available
Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathec...
Article
Full-text available
A simple technique based on doping polymers with in situ generated silver nanoparticles (Ag/PS films) has been developed. In particular, an antiseptic material has been prepared by dissolving silver 1,5-cyclooctadiene-hexafluoroacetylacetonate in amorphous polystyrene, and the obtained solid solution has been heated for ca. 10 s at a convenient tem...
Conference Paper
Orexin-expressing neurons (OX-n) are found in the lateral hypothalamic area (LHA) and project throughout the brain, thereby modulating food intake. In normal mice, the afferents onto OX-n are mostly excitatory and retrogradely modulated by release of endocannabinoids acting through CB1 receptor. This innervation is enhanced by low levels of the hor...
Article
Two oxidation products of linoleic acid, 9- and 13-hydroxy-octadecadienoic acids (HODEs), have recently been suggested to act as endovanilloids, that is, endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) channels, thereby contributing to inflammatory hyperalgesia in rats. However, HODE activity at rat TRPV1 in comparison with...
Article
Full-text available
Primary astrocytomas of grade 3 or 4 according to the classification system of the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among adults and are almost invariably fatal despite the use of multimodal therapy. Here we show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural precursor ce...
Article
Full-text available
To determine the distribution of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) in skin (including hair follicles and sweat and sebaceous glands) of clinically normal dogs and dogs with atopic dermatitis (AD) and to compare results with those for positive control samples for CB1 (hippocampus) and CB2 (lymph nodes). Skin sam...
Conference Paper
Orexin-expressing (OX) neurons are solely found within the lateral hypothalamic area (LHA), from where they send projections throughout the brain, thereby modulating food intake. Food deprivation has been shown to enhance the excitatory input on OX neurons, this enhancement can be reversed by leptin administration. Furthermore, it was shown that th...
Article
Full-text available
Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ9-tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary...
Article
Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromed...
Article
Full-text available
During neuropathic pain, caspases are activated in the limbic cortex. We investigated the role of TRPV1 channels and glial caspases in the mouse prelimbic and infralimbic (PL-IL) cortex after spared nerve injury (SNI). Reverse transcriptase-polymerase chain reaction, western blots, and immunfluorescence showed overexpression of several caspases in...
Article
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Conference Paper
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Neural stem cells express cannabinoid CB1 and CB2 receptors and the enzymes for the biosynthesis and metabolism of endocannabinoids (eCBs). Here we have studied the role of neural stem cell-derived eCBs as autonomous regulatory factors during differentiation. First, we examined the effect of an indirect eCB precursor linoleic acid (LA), a major die...