Dr Castorina began his academic journey at the Department of Anatomy "G.F. Ingrassia" in Catania (Italy) in 2004, where he worked on his Master Degree thesis entitled "Biomechanics of the coxo-femural joint - the positive effects of physical activity". In 2005 he started an internship at the same Department, and had the unique possibilty to receive research training on several molecular and cell biology techniques. Soon after he undertook PhD studies and early in 2009 he received his PhD in Neuropharmacology. For the subsequent 2 years he continued to pursue his molecular studies as a post-doctoral fellow, an appointment that was extended for a 3rd year thanks to his successful scientific achievements. In 2011 he was appointed as Lecturer in Human Anatomy and Neuroanatomy at the University of Catania, and his role was confirmed as Senior four years later.
In 2014 he was awarded an International Research Collaborative Award from the University of Sydney to work in collaboration with the School of Molecular Bioscience. This award gave Dr Castorina the opportunity to also visit Sydney and appreciate this wonderful Country. As a consequence, in September 2015 he took a 1 year sabbatical to join the Discipline of Anatomy & Histology (University of Sydney) as a Research Fellow.
In 2016 Dr Castorina took on a new challenge by deciding to move permanently to Australia and pursue his future academic career here in Sydney. In September 2016 he was appointed as Senior Lecturer in Human Anatomy by the University of Technology Sydney (UTS).
Dr Castorina is now Deputy Discipline Leader for the discipline of Medical Science at UTS. He is also the Head of the Laboratory of Cellular and Molecular Neuroscience (LCMN). In 2019, Dr Castorina also joined the Australial Society for Medical Research NSW State committee, where he is the current Deputy Convenor for the ASM 2019.
Dr Castorina has more than 40 publications in international journals and has authored a book chapter. His current H-Index is 16 (according to Scopus), with more than 500 citations.
Awards & achievements
- May 2016 - Award: International Journal of Molecular Sciences 2016 Best Paper Award for the paper "Ameliorative Effects of PACAP against Cartilage Degeneration. Morphological, Immunohistochemical and Biochemical Evidence from in Vivo and in Vitro Models of Rat Osteoarthritis", link : http://www.mdpi.com/1422-0067/17/5/777/htm
- Aug 2014 - Award: International Research Collaborative Award (IRCA) - Project title "Regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) expression and release in astrocytes from GFAP-Interleukin-6 and GFAP-Interferon-alpha transgenic mice" - (Dr. Castorina - Prof. Campbell) University of Sydney, NSW
- May 2011 - Scholarship: Extension of post-doctoral fellowship
- May 2009 - Scholarship: Post-doctoral fellowship
- Nov 2005 - Scholarship: Ph.D. student scholarship – Externally funded through "Fondo sostegno giovani" – MIUR
Professional memberships, Reviewer & Editorial board activities
Membership to Scientific Societies
· Society for Neuroscience (SFN)
· Società Italiana di Anatomia e Istologia (SIAI) "Italian Society of Anatomy and Histology"
· Australian Pain Society (APS)
Journal Referee Activities
Neurological Research, Neurochemical Research, Current Diabetes Reviews, Life Sciences, Brain Research, Behavioral and Brain Functions,Neuroscience Letters, PLoS ONE, Naunyn-Schmiedeberg's Archives of Pharmacology, Alzheimer's Disease & Parkinsonism, Neuropsychiatric Disease and Treatment, International Journal of Nanomedicine, Neural Regeneration Research, Cell Biochemistry and Function, Toxicology in Vitro, Peptides, Experimental Cell Research, The International Journal of Biochemistry & Cell Biology, Neuroscience, International Journal of Endocrine Oncology
Editorial Board Memberships
· Editorial board member for the journal - NEURAL REGENERATION RESEARCH
· Associate editor for the journal – JACOBS JOURNAL OF ANATOMY & PHYSIOLOGY
· Editorial board member for the journal – NEUROTRANSMITTERS
· Editorial board member for the journal – THERAPEUTIC TARGETS FOR NEUROLOGICAL DISEASES
Commissions of Trust
27/11/2015 – 12/01/2016 Scientific Evaluator for the WHRI-ACADEMY (COFUND Marie Curie) Post-Doctoral Fellowships (4th Call), William Harvey Research Institute, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK
25/03/2015 – 02/06/2015 Scientific Evaluator for the WHRI-ACADEMY (COFUND Marie Curie) Post-Doctoral Fellowships (3rd Call), William Harvey Research Institute, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK
15/11/2014 – 09/02/2015 Scientific Evaluator for the WHRI-ACADEMY (COFUND Marie Curie) Post-Doctoral Fellowships (2nd Call), William Harvey Research Institute, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK
02/04/2014 – present date Member of the Scientific Reviewer Board, Ministero dell’Istruzione, Università e Ricerca (MIUR), Italy
Can supervise: YES
His research interests in the last ten years have been focused on investigating the broad function of two neuroprotective/immunomodulatory neuropeptides known as PACAP and VIP in cellular systems (in vitro) and experimental animals (in vivo), with the aim to get a better understanding of the potential therapeutical implications of these endogenously produced protective molecules in the treatment of neurodegenerative / neuroinflammatory / neurological / neurotraumatic conditions.
A parallel line of research, carried out in collaboration with the Section of Pharmacology at the University of Catania (Italy), has been to comprehend the involvement of dopamine D3 receptors in the development or resilience to addictive behaviors and in mediating dopamine-driven acquisition of fear-related memories.
Having identified many of the potential therapeutical benefits (but also drawbacks) arising from the use of PACAP and VIP in his past research activities, Dr Castorina is now planning to start a new series of investigations with the aim to identify novel upstream post-transcriptional mechanisms governing endogenous PACAP/VIP gene expression in neuronal cells and in rodent models of disease.
Dr Castorina international teaching experience encompasses Human Anatomy in all its aspects, including Musculoskeletal, Visceral, Neuroanatomy and Functional Neuroscience.
He had taught Human Anatomy to both Medical and Science students both in Italy and in Australia. He also taught Visceral and Neuroanatomy in several Allied Health courses, including Neurorehabilation Technicians, Speech Therapy and Orthoptics.
His teaching interests are mainly concentrated in understanding the physical connections between different cortical and subcortical brain structures and their function, but he is also devoted to get deliver to student the knowledge necessary to understand the relationship between the morphology of organ systems and their physiological function.
He lectures and tutors in the subjects Neuroscience (91706) at UTS and for the Notre Dame Medical School (MED1000 and MED2000) and he is the Subject Coordinator for Human Anatomy 2 (91812) and Human Anatomy 3 (91813), two core subjects of the Bachelor of Advanced Sciences.
Castorina, A, Vogiatzis, M, Kang, JWM & Keay, KA 2019, 'PACAP and VIP expression in the periaqueductal grey of the rat following sciatic nerve constriction injury.', Neuropeptides, vol. 74, pp. 60-69.View/Download from: Publisher's site
Nerve injuries often result in neuropathic pain with co-morbid changes in social behaviours, motivation, sleep-wake cycles and neuroendocrine function. In an animal model of neuropathic injury (CCI) similar co-morbid changes are evoked in a subpopulation (~30%) of injured rats. In addition to anatomical evidence of altered neuronal and glial function, the periaqueductal grey (PAG) of these rats shows evidence of cell death. These changes in the PAG may play a role in the disruption of the normal emotional coping responses triggered by nerve injury. Cell death can occur via a number of mechanisms, including the disruption of neuroprotective mechanisms. Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two endogenous neuropeptides whose activities are tightly regulated by two receptors subtypes, namely the PAC1 and VPAC receptors. These peptides and their receptors exert robust neuroprotective roles. In these studies, we hypothesized that rats expressing disabilities following CCI showed altered expression of PACAP and VIP in the PAG. Rats were categorized as having either Pain alone, Transient or Persistent disability, based on changes in social behaviours pre- and post-CCI. Social interaction behavioural tested (BT), sham-injured and naïve untested rats were also included. For measurements of mRNA and protein expression we utilised micro-dissected PAGs blocks taken from each group. At the mRNA level, VIP was downregulated and PAC1 was upregulated in BT animals, whilst VPAC1 mRNA was specifically increased in the Pain alone group. Interestingly, protein levels of both PACAP and VIP were remarkably increased in the Persistent Disability group. Taken together, sciatic nerve CCI that triggers neuropathic pain and persistent disability results in abnormally increased VIP and PACAP expression in the PAG. Our data also suggest that these effects are likely to be governed by post-transcriptional mechanisms.
Castrogiovanni, P, Di Rosa, M, Ravalli, S, Castorina, A, Guglielmino, C, Imbesi, R, Vecchio, M, Drago, F, Szychlinska, MA & Musumeci, G 2019, 'Moderate Physical Activity as a Prevention Method for Knee Osteoarthritis and the Role of Synoviocytes as Biological Key.', International journal of molecular sciences, vol. 20, no. 3.View/Download from: Publisher's site
The purpose of this study was to investigate the influence of moderate physical activity (MPA) on the expression of osteoarthritis (OA)-related (IL-1β, IL-6, TNF-α, MMP-13) and anti-inflammatory and chondroprotective (IL-4, IL-10, lubricin) biomarkers in the synovium of an OA-induced rat model. A total of 32 rats were divided into four groups: Control rats (Group 1); rats performing MPA (Group 2); anterior cruciate ligament transection (ACLT)-rats with OA (Group 3); and, ACLT-rats performing MPA (Group 4). Analyses were performed using Hematoxylin & Eosin (H & E) staining, histomorphometry and immunohistochemistry. In Group 3, OA biomarkers were significantly increased, whereas, IL-4, IL-10, and lubricin were significantly lower than in the other experimental groups. We hypothesize that MPA might partake in rescuing type B synoviocyte dysfunction at the early stages of OA, delaying the progression of the disease.
Leggio, GM, Di Marco, R, Gulisano, W, D'Ascenzo, M, Torrisi, SA, Geraci, F, Lavanco, G, Dahl, K, Giurdanella, G, Castorina, A, Aitta-Aho, T, Aceto, G, Bucolo, C, Puzzo, D, Grassi, C, Korpi, ER, Drago, F & Salomone, S 2019, 'Dopaminergic-GABAergic interplay and alcohol binge drinking.', Pharmacological research, vol. 141, pp. 384-391.View/Download from: Publisher's site
The dopamine D3 receptor (D3R), in the nucleus accumbens (NAc), plays an important role in alcohol reward mechanisms. The major neuronal type within the NAc is the GABAergic medium spiny neuron (MSN), whose activity is regulated by dopaminergic inputs. We previously reported that genetic deletion or pharmacological blockade of D3R increases GABAA α6 subunit in the ventral striatum. Here we tested the hypothesis that D3R-dependent changes in GABAA α6 subunit in the NAc affect voluntary alcohol intake, by influencing the inhibitory transmission of MSNs. We performed in vivo and ex vivo experiments in D3R knockout (D3R -/-) mice and wild type littermates (D3R +/+). Ro 15-4513, a high affinity α6-GABAA ligand was used to study α6 activity. At baseline, NAc α6 expression was negligible in D3R+/+, whereas it was robust in D3R-/-; other relevant GABAA subunits were not changed. In situ hybridization and qPCR confirmed α6 subunit mRNA expression especially in the NAc. In the drinking-in-the-dark paradigm, systemic administration of Ro 15-4513 inhibited alcohol intake in D3R+/+, but increased it in D3R-/-; this was confirmed by intra-NAc administration of Ro 15-4513 and furosemide, a selective α6-GABAA antagonist. Whole-cell patch-clamp showed peak amplitudes of miniature inhibitory postsynaptic currents in NAc medium spiny neurons higher in D3R-/- compared to D3R+/+; Ro 15-4513 reduced the peak amplitude in the NAc of D3R-/-, but not in D3R+/+. We conclude that D3R-dependent enhanced expression of α6 GABAA subunit inhibits voluntary alcohol intake by increasing GABA inhibition in the NAc.
Szychlinska, MA, Di Rosa, M, Castorina, A, Mobasheri, A & Musumeci, G 2019, 'A correlation between intestinal microbiota dysbiosis and osteoarthritis.', Heliyon, vol. 5, no. 1.View/Download from: Publisher's site
Osteoarthritis (OA) is a degenerative disease of the articular cartilage, resulting in pain and total joint disability. Recent studies focused on the role of the metabolic syndrome in inducing or worsening joint damage suggest that chronic low-grade systemic inflammation may represent a possible linking factor. This finding supports the concept of a new phenotype of OA, a metabolic OA. The gut microbiome is fundamental for human physiology and immune system development, among the other important functions. Manipulation of the gut microbiome is considered an important topic for the individual health in different medical fields such as medical biology, nutrition, sports, preventive and rehabilitative medicine. Since intestinal microbiota dysbiosis is strongly associated with the pathogenesis of several metabolic and inflammatory diseases, it is conceivable that also the pathogenesis of OA might be related to it. However, the mechanisms and the contribution of intestinal microbiota metabolites in OA pathogenesis are still not clear. The aim of this narrative review is to review recent literature concerning the possible contribution of dysbiosis to OA onset and to discuss the importance of gut microbiome homeostasis maintenance for optimal general health preservation.
Al-Badri, G & Castorina, A 2018, 'Insights into the Role of Neuroinflammation in the Pathogenesis of Multiple Sclerosis', Journal of Functional Morphology and Kinesiology, vol. 3, no. 1, pp. 1-13.View/Download from: Publisher's site
Multiple sclerosis (MS) is a devastating disease, and with the increasing number of cases each year, it is becoming a significant socioeconomic burden for the affected people and the entire community. The aetiology of MS is largely unknown, but genetic susceptibility, exposure to infections and/or environmental toxicants are recognised as risk factors. MS is characterised by the appearance of lesions/plaques in the central nervous system, caused by destruction of the myelin sheet by auto-reactive T cells. Symptoms range from mild impairment of daily motor functions to severe sensory and cognitive disabilities necessitating mobility assistance, medical and support from caregivers. Due to the progressive nature of the disease, MS is gaining more attention and research to better understand its multifaceted pathogenesis. In the present review, we focus on some of the latest research related to the neuroinflammatory component of the disease, since it appears to play a critical role in MS pathogenesis. The goal is to shed more light on this specific domain of MS, in an attempt to assist in the identification of novel treatment trajectories and management plans.
Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide (GIP), three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells. In this review article, we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions. Finally, we will illustrate some of the promising results obtained using berberine, a plant extract with potent inhibitory activity on DPP-IV.
Musumeci, G, Leggio, GM, Marzagalli, R, Al-Badri, G, Drago, F & Castorina, A 2018, 'Identification of Dysregulated microRNA Networks in Schwann Cell-Like Cultures Exposed to Immune Challenge: Potential Crosstalk with the Protective VIP/PACAP Neuropeptide System.', International journal of molecular sciences, vol. 19, no. 4.View/Download from: Publisher's site
Following peripheral nerve injury, dysregulations of certain non-coding microRNAs (miRNAs) occur in Schwann cells. Whether these alterations are the result of local inflammation and/or correlate with perturbations in the expression profile of the protective vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) system is currently unknown. To address these issues, we aimed at profiling the expression of selected miRNAs in the rat RT4 Schwann cell line. Cells exposed to lipopolysaccharide (LPS), to mimic the local inflammatory milieu, were appraised by real-time qPCR, Western blot and ELISAs. We found that upon LPS treatment, levels of pro-inflammatory cytokines (IL-1β, -6, -18, -17A, MCP-1 and TNFα) increased in a time-dependent manner. Unexpectedly, the expression levels of VIP and PACAP were also increased. Conversely, levels of VPAC1 and VPAC2 receptors were reduced. Downregulated miRNAs included miR-181b, -145, -27a, -340 and -132 whereas upregulated ones were miR-21, -206, -146a, -34a, -155, -204 and -29a, respectively. Regression analyses revealed that a subset of the identified miRNAs inversely correlated with the expression of VPAC1 and VPAC2 receptors. In conclusion, these findings identified a novel subset of miRNAs that are dysregulated by immune challenge whose activities might elicit a regulatory function on the VIP/PACAP system.
Szychlinska, MA, Yamakado, K, Castorina, A & Ljubisavljevic, M 2017, 'The “Journal of Functional Morphology and Kinesiology” Journal Club Series: Highlights on Recent Papers in Musculoskeletal Disorders', Journal of Functional Morphology and Kinesiology, vol. 2, no. 2, pp. 1-6.View/Download from: Publisher's site
Castorina, A, Loreto, C, Vespasiani, G, Giunta, S, Musumeci, G, Castorina, S, Basic, D & Sansalone, S 2016, 'Increased aquaporin 1 expression in the tunica albuginea of Peyronie's disease patients: an in vivo pilot study', HISTOLOGY AND HISTOPATHOLOGY, vol. 31, no. 11, pp. 1241-1249.View/Download from: Publisher's site
Marzagalli, R, Leggio, GM, Bucolo, C, Pricoco, E, Keay, KA, Cardile, V, Castorina, S, Salomone, S, Drago, F & Castorina, A 2016, 'GENETIC BLOCKADE OF THE DOPAMINE D-3 RECEPTOR ENHANCES HIPPOCAMPAL EXPRESSION OF PACAP AND RECEPTORS AND ALTERS THEIR CORTICAL DISTRIBUTION', NEUROSCIENCE, vol. 316, pp. 279-295.View/Download from: Publisher's site
Musumeci, G, Loreto, C, Giunta, S, Rapisarda, V, Szychlinska, MA, Imbesi, R, Castorina, A, Annese, T, Castorina, S, Castrogiovanni, P & Ribatti, D 2016, 'Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers', Experimental Cell Research, vol. 346, no. 1, pp. 91-98.View/Download from: Publisher's site
© 2016 Elsevier Inc.Angiogenesis plays a crucial role in progression of pleural malignant mesothelioma. A significantly increased incidence of pleural mesothelioma has been attributed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. In this study, we have investigated the expression of CD68-positive macrophages, tryptase-positive mast cells and CD31 positive areas, as expression of microvascular density, in lung tissue of sheeps exposed to fluoro-edenite fibers vs controls, by immunohistochemical, morphometric and Western blot analysis. The result have evidenced a significant increase in the expression of CD68-positive macrophages, tryptase-positive mast cells as well as a significant increase in microvascular density evaluated as CD31 positive areas in lung tissue of of sheeps exposed to fluoro-edenite fibers vs controls. These data confirmed the important role played by tumor microenvironment components, including macrophages and mast cells, in favour of angiogenesis in pleural mesothelioma induced by fluoro-edenite exposure.
Castorina, A, Szychlinska, MA, Marzagalli, R & Musumeci, G 2015, 'Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?', NEURAL REGENERATION RESEARCH, vol. 10, no. 6, pp. 850-858.View/Download from: Publisher's site
Castorina, A, Waschek, JA, Marzagalli, R, Cardile, V & Drago, F 2015, 'PACAP Interacts with PAC(1) Receptors to Induce Tissue Plasminogen Activator (tPA) Expression and Activity in Schwann Cell-Like Cultures', PLOS ONE, vol. 10, no. 2.View/Download from: Publisher's site
Giunta, S, Castorina, A, Marzagalli, R, Szychlinska, MA, Pichler, K, Mobasheri, A & Musumeci, G 2015, 'Ameliorative Effects of PACAP against Cartilage Degeneration. Morphological, Immunohistochemical and Biochemical Evidence from in Vivo and in Vitro Models of Rat Osteoarthritis', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 16, no. 3, pp. 5922-5944.View/Download from: Publisher's site
Leggio, GM, Torrisi, SA, Castorina, A, Platania, CBM, Impellizzeri, AAR, Fidilio, A, Caraci, F, Bucolo, C, Drago, F & Salonnone, S 2015, 'Dopamine D3 receptor-dependent changes in alpha6 GABAA subunit expression in striatum modulate anxiety-like behaviour: Responsiveness and tolerance to diazepam', EUROPEAN NEUROPSYCHOPHARMACOLOGY, vol. 25, no. 9, pp. 1427-1436.View/Download from: Publisher's site
Marzagalli, R & Castorina, A 2015, 'The seeming paradox of adenosine receptors as targets for the treatment of Alzheimer's disease: agonists or antagonists?', NEURAL REGENERATION RESEARCH, vol. 10, no. 2, pp. 205-207.View/Download from: Publisher's site
Marzagalli, R, Scuderi, S, Drago, F, Waschek, JA & Castorina, A 2015, 'Emerging Role of PACAP as a New Potential Therapeutic Target in Major Diabetes Complications', INTERNATIONAL JOURNAL OF ENDOCRINOLOGY.View/Download from: Publisher's site
Musumeci, G, Castorina, A, Magro, G, Cardile, V, Castorina, S & Ribatti, D 2015, 'Enhanced expression of CD31/platelet endothelial cell adhesion molecule 1 (PECAM1) correlates with hypoxia inducible factor-1 alpha (HIF-1 alpha) in human glioblastoma multiforme', EXPERIMENTAL CELL RESEARCH, vol. 339, no. 2, pp. 407-416.View/Download from: Publisher's site
Musumeci, G, Magro, G, Cardile, V, Coco, M, Marzagalli, R, Castrogiovanni, P, Imbesi, R, Graziano, ACE, Barone, F, Di Rosa, M, Castorina, S & Castorina, A 2015, 'Characterization of matrix metalloproteinase-2 and-9, ADAM-10 and N-cadherin expression in human glioblastoma multiforme', CELL AND TISSUE RESEARCH, vol. 362, no. 1, pp. 45-60.View/Download from: Publisher's site
Castorina, A & Giunta, S 2014, 'Mucin 1 (MUC1) signalling contributes to increase the resistance to cell death in human bronchial epithelial cells exposed to nickel acetate', BIOMETALS, vol. 27, no. 6, pp. 1149-1158.View/Download from: Publisher's site
Castorina, A, Scuderi, S, D'Amico, AG, Drago, F & D'Agata, V 2014, 'PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways', EXPERIMENTAL CELL RESEARCH, vol. 322, no. 1, pp. 108-121.View/Download from: Publisher's site
Giunta, S, Andriolo, V & Castorina, A 2014, 'Dual blockade of the A(1) and A(2A) adenosine receptor prevents amyloid beta toxicity in neuroblastoma cells exposed to aluminum chloride', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 54, pp. 122-136.View/Download from: Publisher's site
Leggio, GM, Camillieri, G, Platania, CBM, Castorina, A, Marrazzo, G, Torrisi, SA, Nona, CN, D'Agata, V, Nobrega, J, Stark, H, Bucolo, C, Le Foll, B, Drago, F & Salomone, S 2014, 'Dopamine D3 Receptor Is Necessary for Ethanol Consumption: An Approach with Buspirone', NEUROPSYCHOPHARMACOLOGY, vol. 39, no. 8, pp. 2017-2028.View/Download from: Publisher's site
Scuderi, S, D'Amico, AG, Castorina, A, Federico, C, Marrazzo, G, Drago, F, Bucolo, C & D'Agata, V 2014, 'Davunetide (NAP) Protects the Retina Against Early Diabetic Injury by Reducing Apoptotic Death', JOURNAL OF MOLECULAR NEUROSCIENCE, vol. 54, no. 3, pp. 395-404.View/Download from: Publisher's site
Castorina, A, D'Amico, AG, Scuderi, S, Leggio, GM, Drago, F & D'Agata, V 2013, 'DOPAMINE D-3 RECEPTOR DELETION INCREASES TISSUE PLASMINOGEN ACTIVATOR (TPA) ACTIVITY IN PREFRONTAL CORTEX AND HIPPOCAMPUS', NEUROSCIENCE, vol. 250, pp. 546-556.View/Download from: Publisher's site
D'Amico, AG, Castorina, A, Leggio, GM, Drago, F & D'Agata, V 2013, 'Hippocampal Neurofibromin and Amyloid Precursor Protein Expression in Dopamine D-3 Receptor Knock-out Mice Following Passive Avoidance Conditioning', NEUROCHEMICAL RESEARCH, vol. 38, no. 3, pp. 564-572.View/Download from: Publisher's site
D'Amico, AG, Castorina, A, Leggio, GM, Imbesi, R, Drago, F & D'Agata, V 2013, 'Dopamine D3 receptor knockout mice exhibit increased hippocampal cAMP response element binding protein (CREB) following acquisition of passive avoidance memory', Italian Journal of Anatomy and Embryology, vol. 118, no. 2 SUPPL.
D'Amico, AG, Scuderi, S, Leggio, GM, Castorina, A, Drago, F & D'Agata, V 2013, 'Increased Hippocampal CREB Phosphorylation in Dopamine D3 Receptor Knockout Mice Following Passive Avoidance Conditioning', NEUROCHEMICAL RESEARCH, vol. 38, no. 12, pp. 2516-2523.View/Download from: Publisher's site
D'Amico, AG, Scuderi, S, Saccone, S, Castorina, A, Drago, F & D'Agata, V 2013, 'Antiproliferative Effects of PACAP and VIP in Serum-Starved Glioma Cells', JOURNAL OF MOLECULAR NEUROSCIENCE, vol. 51, no. 2, pp. 503-513.View/Download from: Publisher's site
Scuderi, S, D'Amico, AG, Castorina, A, Imbesi, R, Carnazza, ML & D'Agata, V 2013, 'Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction', PEPTIDES, vol. 39, pp. 119-124.View/Download from: Publisher's site
Bucolo, C, Leggio, GM, Maltese, A, Castorina, A, D'Agata, V & Drag, F 2012, 'Dopamine-(3) receptor modulates intraocular pressure: Implications for glaucoma', BIOCHEMICAL PHARMACOLOGY, vol. 83, no. 5, pp. 680-686.View/Download from: Publisher's site
Castorina, A, Giunta, S, Scuderi, S & D'Agata, V 2012, 'Involvement of PACAP/ADNP Signaling in the Resistance to Cell Death in Malignant Peripheral Nerve Sheath Tumor (MPNST) Cells', JOURNAL OF MOLECULAR NEUROSCIENCE, vol. 48, no. 3, pp. 674-683.View/Download from: Publisher's site
Giunta, S, Castorina, A, Bucolo, C, Magro, G, Drago, F & D'Agata, V 2012, 'Early changes in pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and related receptors expression in retina of streptozotocin-induced diabetic rats', PEPTIDES, vol. 37, no. 1, pp. 32-39.View/Download from: Publisher's site
Giunta, S, Castorina, A, Scuderi, S, Patti, C & D'Agata, V 2012, 'Epidermal growth factor receptor (EGFR) and neuregulin (Neu) activation in human airway epithelial cells exposed to nickel acetate', TOXICOLOGY IN VITRO, vol. 26, no. 2, pp. 280-287.View/Download from: Publisher's site
Castorina, A, Leggio, GM, Giunta, S, Magro, G, Scapagnini, G, Drago, F & D'Agata, V 2011, 'Neurofibromin and Amyloid Precursor Protein Expression in Dopamine D3 Receptor Knock-Out Mice Brains', NEUROCHEMICAL RESEARCH, vol. 36, no. 3, pp. 426-434.View/Download from: Publisher's site
Loreto, C, Musumeci, G, Castorina, A, Loreto, C & Martinez, G 2011, 'Degenerative disc disease of herniated intervertebral discs is associated with extracellular matrix remodeling, vimentin-positive cells and cell death', ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, vol. 193, no. 2, pp. 156-162.View/Download from: Publisher's site
Castorina, A, Giunta, S & D'Agata, V 2010, 'Protective effect of the dopamine D3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells', International Journal of Oncology, vol. 37, no. 4, pp. 927-934.View/Download from: Publisher's site
Emerging evidence indicates that the dopamine D3 receptor (D3R) mediates protective roles both in neuronal and non-neuronal cell lines. In a previous study we proposed that neurofibromin, a large tumor suppressor protein encoded by the neurofibromatosis type 1 gene (NF1), may increase susceptibility to apoptosis after serum deprivation in malignant peripheral nerve sheath tumor (MPNST) cells, thus acting as a proapoptotic gene. In addition, it has been observed that D3Rs are functionally correlated to neurofibromin. In this study, we examined whether 7-OH-PIPAT, a potent dopamine D3R agonist, exerts an antiapoptotic role under the same culture conditions and then correlated this effect to changes in NF1 expression. Results showed that serum deprivation caused a significant reduction of cell viability (MTT assay) both after 24 and 48 h (p<0.001). Treatment with increasing concentrations of 7-OH-PIPAT (10-9-10-5 M) induced a progressive increase in cell viability both after 24 and 48 h as compared to vehicle-treated cells, with significant changes at the highest concentrations tested (10-6 and 10-5 M). Consistently, at the latter two concentrations, a significant reduction in oligonucleosomes formation was observed, thus suggesting an antiapoptotic role of 7-OH-PIPAT. These results were confirmed by Hoechst 33254 nuclear staining. To investigate whether these effects were correlated to changes in NF1 transcript and protein expression, quantitative real-time PCR, Western blot and immunofluorescence analyses were performed. Results demonstrated that the upregulation of NF1 transcripts and protein levels induced by serum withdrawal were remarkably attenuated by 10-6 and 10-5 M agonist treatment within 24 h (p<0.01 and p<0.001, respectively), whereas similar effects were observed already at a lower concentration (10-7 M) after 48 h treatment (p<0.001). In conclusion, these results suggest that D3R might mediate the protective response to serum deprivation in MPNST cell...
Castorina, A, Giunta, S & D'Agata, V 2010, 'Protective effect of the dopamine D-3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells', INTERNATIONAL JOURNAL OF ONCOLOGY, vol. 37, no. 4, pp. 927-934.View/Download from: Publisher's site
Castorina, A, Giunta, S, Mazzone, V, Cardile, V & D'Agata, V 2010, 'Effects of PACAP and VIP on hyperglycemia-induced proliferation in murine microvascular endothelial cells', PEPTIDES, vol. 31, no. 12, pp. 2276-2283.View/Download from: Publisher's site
Castorina, A, Tiralongo, A, Giunta, S, Carnazza, ML, Scapagnini, G & D'Agata, V 2010, 'Early effects of aluminum chloride on beta-secretase mRNA expression in a neuronal model of -amyloid toxicity', CELL BIOLOGY AND TOXICOLOGY, vol. 26, no. 4, pp. 367-377.View/Download from: Publisher's site
Giunta, S, Castorina, A, Adorno, A, Mazzone, V, Carnazza, ML & D'Agata, V 2010, 'PACAP and VIP affect NF1 expression in rat malignant peripheral nerve sheath tumor (MPNST) cells', NEUROPEPTIDES, vol. 44, no. 1, pp. 45-51.View/Download from: Publisher's site
D'Agata, V, Tiralongo, A, Castorina, A, Leggio, GM, Micale, V, Carnazza, ML & Drago, F 2009, 'Parkin Expression Profile in Dopamine D3 Receptor Knock-Out Mice Brains', NEUROCHEMICAL RESEARCH, vol. 34, no. 2, pp. 327-332.View/Download from: Publisher's site
Castorina, A, Tiralongo, A, Cavallo, D, Loreto, C, Carnazza, ML, Iavicoli, S & D'Agata, V 2008, 'Expression profile of ErbB receptor's family in human alveolar type 2-like cell line A549 exposed. to hexavalent chromium', TOXICOLOGY IN VITRO, vol. 22, no. 2, pp. 541-547.View/Download from: Publisher's site
Castorina, A, Tiralongo, A, Giunta, S, Carnazza, ML, Rasi, G & D'Agata, V 2008, 'PACAP and VIP prevent apoptosis in schwannoma cells', BRAIN RESEARCH, vol. 1241, pp. 29-35.View/Download from: Publisher's site
Szychlinska, MA, Calabrese, G, Ravalli, S, Dolcimascolo, A, Castrogiovanni, P, Fabbi, C, Puglisi, C, Lauretta, G, Di Rosa, M, Castorina, A, Parenti, R & Musumeci, G, 'Evaluation of a Cell-Free Collagen Type I-Based Scaffold for Articular Cartilage Regeneration in an Orthotopic Rat Model', Materials, vol. 13, no. 10, pp. 2369-2369.View/Download from: Publisher's site
The management of chondral defects represents a big challenge because of the limited self-healing capacity of cartilage. Many approaches in this field obtained partial satisfactory results. Cartilage tissue engineering, combining innovative scaffolds and stem cells from different sources, emerges as a promising strategy for cartilage regeneration. The aim of this study was to evaluate the capability of a cell-free collagen I-based scaffold to promote cartilaginous repair after orthotopic implantation in vivo. Articular cartilage lesions (ACL) were created at the femoropatellar groove in rat knees and cell free collagen I-based scaffolds (S) were then implanted into right knee defect for the ACL-S group. No scaffold was implanted for the ACL group. At 4-, 8- and 16-weeks post-transplantation, degrees of cartilage repair were evaluated by morphological, histochemical and gene expression analyses. Histological analysis shows the formation of fibrous tissue, at 4-weeks replaced by a tissue resembling the calcified one at 16-weeks in the ACL group. In the ACL-S group, progressive replacement of the scaffold with the newly formed cartilage-like tissue is shown, as confirmed by Alcian Blue staining. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses display the expression of typical cartilage markers, such as collagen type I and II (ColI and ColII), Aggrecan and Sox9. The results of this study display that the collagen I-based scaffold is highly biocompatible and able to recruit host cells from the surrounding joint tissues to promote cartilaginous repair of articular defects, suggesting its use as a potential approach for cartilage tissue regeneration.
Karunia, J, Niaz, A, Mandwie, M, Al-Badri, G & Castorina, A 2019, 'DISTINCT PHENOTYPIC CHANGES BY PACAP AND VIP IN LIPOPOLYSACCHARIDE STIMULATED BV2 MICROGLIAL CELLS', Akira Arimura Memorial VIP/PACAP and Related Peptides Symposium: 30 years after PACAP Discovery, Los Angeles, California.
Background: Aberrant microglial activation plays a key role in the progressive neuronal loss seen in many neurodegenerative diseases. PACAP and VIP are two neuropeptides that elicit robust immunosuppressive functions within the CNS. However, the underlying mechanisms through which these peptides regulate microglia activities are not clear.
Aim & Objectives: Using lipopolysaccharide (LPS) to induce BV2 microglial cell polarisation, we aimed at testing whether and how administration of either PACAP or VIP could differentially affect microglial pro-inflammatory profile, polarisation state and morphological appearance to elicit immunosuppressive effects.
Methods: Quantitative real-time PCR, Western blot, Griess reactions, immunofluorescence and morphological analyses were conducted in order to determine the effects of PACAP and VIP in BV2 microglial cells exposed or not to 1µg/ml LPS.
Results: Our data demonstrated that both PACAP and VIP reduce the expression of pro-inflammatory mediators in LPS-stimulated BV2 cells. We also found that exogenous administration of PACAP and VIP rescued the dysregulations of the endogenous PACAP/VIP levels and attenuated the expression of microglial activation markers caused by LPS. Interestingly, despite the similar anti-inflammatory activities of PACAP and VIP, PACAP mainly reduced the number of M1 polarised cells, whereas VIP acted by increasing the subpopulation of cells exhibiting an ‘intermediate’ phenotype/bipolar-shaped (p<0.001 vs. control), at the expenses of resting/rounded cells.
Conclusion: PACAP and VIP both possess immunosuppressive effects in activated BV2 microglial cells, but these effects seem to involve the differential shift of certain cell subpopulations towards distinctive phenotypes.
Castorina, A, Kang, JWM, Vogiatzis, M, Kalman, E & Keay, KA 2017, 'Effects of neuropathic injury on the expression profile of PACAP family members in the rat brain', Australasian Neuroscience Society meeting 2017, ICC Darling Harbour, Sydney.
Dr. Castorina has succeeded to establish productive collaborations with eminent scientists worldwide (UCLA, California, USA, The University of Sydney, Australia, University of Catania, Italy) with common interest in the field of neuroscience.
Prof. James A. Waschek - Semel Institute for Neuroscience and Human Behavior (UCLA)
"Studied PACAP function in Schwann cells"
Prof. Filippo Drago / Dr Gian Marco Leggio - Department Biomedical and Biotechnological Sciences (BIOMETEC), (University of Catania, Italy)
"Dopamine D3 receptor role in alcohol addiction and memory function"
Prof. Iain Campbell - School of Molecular Biosciences, (UNISYD)
"Investigate the endogenous regulation of the PACAP/VIP system in transgenic mice overexpressing different cytokines in astrocytes"
Assoc./Prof. Kevin A. Keay - Discipline of Anatomy & Histology, Laboratory of Neuronal Structure and Function (LNSF, UNISYD)
"Identify a potential correlation between PACAP system dysregulation in the brain and the development of behavioral abnormalities in experimental rat models of neuropathic pain"