Interspecies study of the enteric nervous system and related pathologies

The enteric nervous system (ENS) modulates a number of digestive functions including well known ones, i.e. motility, secretion, absorption and blood flow, along with other critically relevant processes, i.e. immune responses of the gastrointestinal (GI) tract, gut microbiota and epithelial barrier . The characterization of the anatomical aspects of the ENS in large mammals and the identification of differences and similarities existing between species may represent a fundamental basis to decipher several digestive GI diseases in humans and animals. In this perspective, the aim of the present thesis is to highlight the ENS anatomical basis and pathological aspects in different mammalian species, such as horses, dogs and humans. Firstly, I designed two anatomical studies in horses:  “Excitatory and inhibitory enteric innervation of horse lower esophageal sphincter”.  “Localization of 5-hydroxytryptamine 4 receptor (5-HT4R) in the equine enteric nervous system”. Then I focused on the enteric dysfunctions, including:  A primary enteric aganglionosis in horses: “Extrinsic innervation of the ileum and pelvic flexure of foals with ileocolonic aganglionosis”.  A diabetic enteric neuropathy in dogs: “Quantification of nitrergic neurons in the myenteric plexus of gastric antrum and ileum of healthy and diabetic dogs”.  An enteric neuropathy in human neurological patients: “Functional and neurochemical abnormalities in patients with Parkinson's disease and chronic constipation”. The physiology of the GI tract is characterized by a high complexity and it is mainly dependent on the control of the intrinsic nervous system. ENS is critical to preserve body homeostasis as reflect by its derangement occurring in pathological conditions that can be lethal or seriously disabling to humans and animals. The knowledge of the anatomy and the pathology of the ENS represents a new important and fascinating topic, which deserves more attention in the veterinary medicine field.

Unraveling the pathophysiological mechanisms of visceral pain in the murine model of Fabry disease

Fabry disease (FD) is an X‐linked inherited, lysosomal storage disorder characterized by a deficient activity of the enzyme α-Galactosidase A (α-Gal A). This deficiency causes an accumulation of globotriaosylceramide 3 (Gb3), in nearly all organs. Gastrointestinal (GI) symptoms are among the earliest and most frequent symptoms of FD. It has been hypothesized that Gb3 accumulation is the leading cause of these, but their pathophysiology is complex and still poorly understood. Here, we aim at understanding the molecular mechanisms underpinning the GI symptoms of FD. For this purpose, we used the α‐Gal A (-/0) male mouse, a murine model of FD, to characterize morphological and molecular features of the colon tract. Our results show that α‐Gal A (-/0) mice display a thickening of the muscular layer due to a hypertrophic state of myenteric plexus ganglia, caused by an accumulation of Gb3 in neurons. Also, α-Gal A (-/0) mice present a decreased density of mucosal nerve fibres. Furthermore, α-Gal A (-/0) mice presented visceral hyperalgesia, by showing greater visceromotor response (VMR) values and obtaining higher abdominal withdrawal reflex (AWR) scores, following colorectal distension (CRD). Subsequently, the immunoreactivity of the pain-related ion channels TRPV1, TRPV4, TRPA1 and TRPM8 was detected at level of myenteric and submucosal plexus ganglia of both the genotypes. Further studies are required to assess differences of expression between α-Gal A (-/0) and control mice. Finally, we optimized the protocols to obtain three types of primary cultures from mouse intestine to be tested electrophysiologically: a mixed culture containing neurons and glia, an enriched culture of neurons, and one of glia. In summary, we revealed alterations that are likely to be part of the pathophysiological causes of FD GI symptoms. Therefore, together with further studies, this work could help identify new therapeutic targets for the treatment of visceral pain in FD.

Ruolo dell'attività di arrampicata nel percorso abilitativo del bambino affetto da Paralisi Cerebrale Infantile: Scoping Review

Background: La paralisi cerebrale infantile (PCI) è una frequente causa di disabilità nei bambini e nei giovani adulti. Consiste in un gruppo di disturbi neurologici permanenti che causano primariamente limitazioni e disfunzioni nello sviluppo motorio; a tali disturbi possono associarsi problematiche sensoriali e cognitive. Una specifica Arrampicata sportiva, mediante una parete adattiva, può essere un’interessante attività terapeutica da associare al tradizionale programma abilitativo per i bambini con PCI. Obiettivo: L’obiettivo di questa Scoping Review è quello di andare a studiare, approfondire e sintetizzare le evidenze della ricerca rispetto al ruolo della parete di arrampicata come attività aggiuntiva e di sostegno all’interno del progetto abilitativo dei bambini affetti da paralisi cerebrale infantile. Metodi: La ricerca sistematica e bibliografica è stata realizzata mediante la consultazione di banche dati, riviste di giornali e grey literature. È stata effettuata un’analisi degli articoli pertinenti rispetto al quesito clinico di partenza: “Cosa ci dice la Letteratura esistente in merito al ruolo dell’attività di Arrampicata nel percorso abilitativo del bambino affetto da Paralisi Cerebrale Infantile?”. Risultati: Dalla selezione sono stati inclusi 8 articoli, eterogenei tra loro rispetto alla tipologia di studio. Il processo di selezioni delle fonti di evidenza è stato riepilogato tramite un diagramma di flusso. I contenuti di ogni articolo sono stati schematizzati in una tabella sinottica e in seguito sintetizzati per ciascuno obiettivo dello studio, partecipanti, intervento e risultati. Conclusioni: I risultati mostrano come nei bambini con PCI un’adattata attività di arrampicata, inserita in un programma fisioterapico, sia uno strumento terapeutico aggiuntivo nel determinare un miglioramento della mobilità e del controllo motorio, principalmente di arti superiori, in funzione di un maggior sviluppo delle abilità nelle ADL.