Claudia Cristiano's research while affiliated with University of Aberdeen and other places

Publications (51)

Article
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Neurodegenerative diseases (NDDs) are characterized by cognitive impairment and behavioural abnormalities. The incidence of NDDs in recent years has increased globally and the pathological mechanism is not fully understood. To date, plentiful evidence has showed that metabolic alterations associated with obesity and related issues such as neuroinfl...
Article
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Objective Overweight and obesity are endemic in developed countries, with a substantial negative impact on human health. Medications developed to treat obesity include agonists for the G-protein coupled receptors glucagon-like peptide-1 (GLP-1R; e.g. liraglutide), serotonin 2C (5-HT2CR; e.g, lorcaserin), and melanocortin4 receptor (MC4R) which redu...
Article
Several studies indicate a relationship between maternal gut microbiota alteration and increased risk of autism spectrum disorders (ASD) in offspring. The possibility of compensating for such metabolic dysfunction at a very early stage of disease via maternal treatment has not been enough explored. Here, we examined in BTBR mouse model of ASD the e...
Article
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The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut–brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain...
Article
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Paclitaxel (PTX) is one of the most broadly used chemotherapeutic agents for the treatment of several tumor types including ovarian, breast, and non-small cell lung cancer. However, its use is limited by debilitating side effects, involving both gastrointestinal and behavioral dysfunctions. Due to growing evidence showing a link between impaired gu...
Article
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Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic drugs, particularly paclitaxel (PTX). It can affect the quality of patients’ lives and increase the risk of developing mood disorders. Although several drugs are recommended, they yielded inconclusive results in clinical trials. The aim of the present work...
Preprint
Overweight and obesity are rapidly becoming the new normal in developed countries, which promotes a widespread negative impact on human health. Amongst recently developed obesity medications are the serotonin 2C receptor (5-HT 2C R) agonist lorcaserin and glucagon-like peptide-1 receptor (GLP-1R) agonists, but the brain circuits employed by these m...
Article
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Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-i...
Article
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Carbohydrates are one of the most abundant and important classes of biomolecules. The variety in their structures makes them valuable carriers that can improve the pharmaceutical phase, pharmacokinetics and pharmacodynamics of well-known drugs. D-galactose is a simple, naturally occurring monosaccharide sugar that has been extensively studied for u...
Article
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Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by social deficits, repetitive stereotyped behaviors, and altered inflammatory responses. Accordingly, children with ASD show decreased plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation, which is the endog...
Article
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Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target...
Article
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Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibit...
Article
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In our previous studies, a ketorolac–galactose conjugate (ketogal) showed prolonged anti-inflammatory and analgesic activity, causing less gastric ulcerogenic effect and renal toxicity than its parent drug ketorolac. In order to demonstrate the safer profile of ketogal compared to ketorolac, histopathological changes in the small intestine and live...
Article
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Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for th...
Article
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Pain conditions, such as neuropathic pain (NP) and persistent inflammatory pain are therapeutically difficult to manage. Previous studies have shown the involvement of glutamate receptor in pain modulation and in particular same of these showed the key role of the AMPA ionotropic glutamate receptor subtype. Antiseizure medications (ASMs) are often...
Article
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Inflammatory bowel disorders can be associated with alterations in gut microbiota (dysbiosis) and behavioral disturbances. In experimental colitis, administration of fish oil (FO) or cannabinoids, such as cannabidiol (CBD), reduce inflammation. We investigated the effect of combined FO/CBD administration on inflammation and dysbiosis in the dextran...
Article
Convergent lines of evidence have recently highlighted β3‐adrenoreceptors (ARs) as a potentially critical target in the regulation of nervous and behavioral functions, including memory consolidation, anxiety, and depression. Nevertheless, the role of β3‐ARs in the cerebellum has been never investigated. To address this issue, we first examined the...
Article
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Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, a series of conformationally restricted derivatives of the previously described TRPM8 antagonist N,N′-dibenzyl tryptophan 4 were prepared and characterized in vitro by Ca²⁺-imaging and patch-clamp electroph...
Article
Given the high‐energy requirements to sustain immune responses and healing processes, it is intriguing that lack of appetite (i.e. anorexia) is a cardinal feature of sickness behaviour. While our understanding of the brain mechanisms that control appetite is rapidly growing, how inflammation impacts on these mechanisms is not fully understood. Here...
Article
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There is a strong relationship between palatable diet and pain sensitivity, and the cannabinoid and opioid systems might play an important role in this correlation. The palatable diet used in many animal models of obesity is the cafeteria (CAF) diet, based on human food with high sugar, salt, and fat content. In this study, we investigated whether...
Article
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Traumatic brain injury (TBI) represents an important public health problem and is followed by neuroinflammation and neurological dysfunctions. It has been suggested that brain trauma is often associated with deep behavioral alterations and chronic pain-like syndrome. Despite inducing minimal brain damage, mild TBI (mTBI) leads to persistent behavio...
Article
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Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported th...
Article
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The use/misuse of antibiotics leads to pathological features referring to antibiotic-induced intestinal injury (AIJ), a clinical issue that plays a prominent role in the development of severe digestive disturbances. AIJ is characterized by loss of intestinal architecture and function, dysbiosis and bacterial translocation into the liver, triggering...
Article
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Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, t...
Article
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Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by impaired social interaction, and repetitive stereotyped behaviours. Interestingly, functional and inflammatory gastrointestinal diseases are often reported as a comorbidity in ASDs, indicating gut-brain axis as a novel emerging approach. Rece...
Article
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To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT2CR) improve obesity. Here we probed the functional significance of 5-HT2CRs specifically within the brainstem nucleus of the solitary tract (5...
Article
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Pre- and post-natal factors can affect brain development and function, impacting health outcomes with particular relevance to neurodevelopmental diseases, such as autism spectrum disorders (ASDs). Maternal obesity and its associated complications have been related to the increased risk of ASDs in offspring. Indeed, animals exposed to maternal obesi...
Article
It has been suggested that the bioactive lipid mediator oleoylethanolamide (OEA), a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α) possesses anti-depressant-like effects in several preclinical models. We recently demonstrated that several of OEA's behavioural actions require the integrity of the brain histaminergic...
Article
Background and purpose: Transient receptor potential (TRP) channels are a superfamily of non-selective cation permeable channels involved in peripheral sensory signalling. Animal studies have shown that several TRPs are relevant players in pain modulation. Among them, the TRP Melastatin8 (TRPM8) has elicited more interest for its controversial rol...
Article
The increasing use of plant medicines (herbals) in Europe needs a shared methodology to determine the toxicity and the daily exposure level to these drugs. For this reason, the European regulatory agencies have undertaken a study that could meet popular uses and toxicological research in different countries of the Union. Here we list some examples...
Article
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Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated...
Article
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Objective: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, s...
Article
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Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestin...
Article
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The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence en...
Article
Several pathogenetic factors have been involved in the onset and progression of Parkinson's disease (PD), including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Palmitoylethanolamide (PEA), an endogenous N-acylethanolamine, has been shown to be a neuroprotective and anti-inflammatory molecule, acting as a peroxisome...
Article
paragraph Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that has an essential role in the regulation of emotion. The precise circuits through which aversive states are orchestrated by 5-HT, however, have not yet been defined. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpo...
Article
In the present study we investigated the role of sodium butyrate (butyrate), and its more palatable derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), in animal models of acute and chronic pain. We found that oral administrations of butyrate (10-200mg/Kg) or equimolecular FBA (21.2-424mg/Kg) reduced visceral pain in a dose- and time-d...
Article
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Nuclear peroxisome proliferator activated receptor-α (PPAR-α) plays a fundamental role in the regulation of lipid homeostasis and is the target of medications used to treat dyslipidemia. However, little is known about the role of PPAR-α in mouse behavior. To investigate the function of Ppar-α in cognitive functions, a behavioral phenotype analysis...
Article
The neuropeptide oxytocin (OXT) contributes to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Although many authors have reported the analgesic effects of OXT, its mechanism has not been...
Article
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Alzheimer disease (AD) is the most common form of neurodegenerative dementia. Amyloid-β deposition, neurofibrillary tangle formation, and neuro-inflammation are the major pathogenic mechanisms that in concert lead to memory dysfunction and decline of cognition. Palmitoylethanolamide (PEA) is the naturally occurring lipid amide between palmitic acid...

Citations

... However, most of these therapies exhibited moderate efficacy and significant side effects such as somnolence, constipation, tolerance, and dizziness [60]. In addition, some treatments only improved neuropathy or one of the emotional disorders associated with chemotherapy-induced neuropathic pain [61][62][63], but only a few studies evaluated the possible effects of different treatments in the management of PIPN-associated mood disorders [13,64,65]. In this line, this study demonstrated that treatment with HRW inhibited neuropathy and avoided the cognitive and emotional deficits associated. ...
... Butyrate produced mainly by bacterial fermentation of fibre in the colon has been extensively investigated, from a pharmacological point of view, for its several bio-functional activities [19] and its therapeutic activities against colon cancer, ischemic stroke, hemoglobinopathies and cerebral diseases [19,41,42]. Our results showed that the administration of butyrate to HFD-treated mice results in a significant improvement of obesityrelated alterations of body composition and metabolic parameters. ...
... Furthermore, the number of regulatory T lymphocytes (Treg) decreases [109,110]. Recently, Brandolini, d'Angelo [111]demonstrated that PTX binds and activates complement component 5a receptor 1 (C5aR1) which is involved in PIPN as well as PTX-induced anaphylaxis. PTX-activated immune cells secrete a plethora of inflammatory mediators, such as interleukins (IL): IL-1β [112], IL-6 [113], IL-8 [114], tumor necrosis factor α (TNFα), and interferon γ (IFNγ)] and chemokines (e.g., CCL2, and CXCL12, CCL11, CCL3, and CCL4) [115], all are implicated in precipitation of neuropathy. ...
... NSAIDS can only suppress the symptoms like pain despite it can cause severe side effects. Therefore, the focus has been turned towards herbal medicine (Petrovska, 2012;Sodano et al., 2022). ...
... Many studies have reported that immune system complications are common in ASD and are accompanied by increased activation of brain glial cells and increased levels of interferon, interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor (TNF)-α [18,19]. It has also been reported that long-term neuronal inflammation is associated with reduced social behavior, which is comparable to the response of children exposed prenatally to VPA [20]. Furthermore, several previous studies have suggested the role of certain brain neurotransmitters in the early stages of brain development and are associated with the onset and development of ASD [1]. ...
... We applied the galactosylated prodrug strategy to a number of NSAIDs. The first successful example of this approach was Ketogal [25], with ACEgal and PARgal then following [26,27]. In each study, the galactosylated prodrug showed marked improvements, compared with its parent drug, in some or all of its physicochemical, pharmacokinetic, pharmacodynamic and toxicological parameters. ...
... The neuroprotective action of PEAOXA not only leads to a decrease in alterations and damage associated with inflammation but is also reflected in improvements in the behavioural sphere. In fact, PEAOXA was shown to improve depressive-like and anxiety-associated behaviours in a mouse model of neuropathic pain [14]. ...
... The activated immune cells lead to the release of several mediators from the damaged peripheral sensory neurons such as high mobility group box-1 (HMBG1), fibronectin, and heat shock proteins which triggers neuronal inflammation, hyperexcitability and potentiation of pain. Similarly, PTX-induced changes in microbiota and gut barrier dysfunction results in elevated systemic exposure to bacterial metabolites, which drives pain sensitivity [98,99]. Paclitaxel has been associated with enhanced activation of neuronal toll-like receptors, TLR2, TLR4 and TLR9. ...
... Most evidence regarding a potential therapeutic effect of PEA in NCDs was gathered from preclinical studies administering the compound to animal models of NCDs (Table 1B), including AD (20,31,38,46,47,50), Aβ-exposed (34), middle cerebral artery occlusion (MCAo) (24), PD (39), vascular dementia (VaD) (36, 42), spared nerve injury (SNI) (40,41,49), TBI (28), Complete Freund's Adjuvant (CFA) (51), and high-fat diet (48) models. Despite the evidence of similar methodologies across the reviewed studies, a certain heterogeneity was found in terms of animal type [mice (20, 28, 31, 36, 38-42, 46, 48-50), rat (24,34,47,51)], period of exposure [from 4 to 5 weeks old to 21 months old), PEA formulation [alone unspecified,PEA (31,34,50,51); alone micronized, PEAm (39); alone ultra-micronized, um-PEA (20,38,40,41,46,48); combined with oxazoline, 49); combined with luteolin, PEALut (24,28,36,47)], PEA mode of administration [intraperitoneal (34,40,41,47,49,51), subcutaneous (20,31,38), oral (24,28,36,39,42,46,48,50)], dosage of PEA [2 to 10 mg/kg for intraperitoneal administration (34,40,41,47,49,51), 3 to 30 mg/kg for subcutaneous (20,31,38), 1 to 100 mg/kg for oral administration (24,28,36,39,42,46,48,50)], and duration of exposure (from single administration to 3 months) (Table 2B). ...