Parkinson's disease and gastrointestinal dysfunctions: morphological, neurochemical and functional modifications of the enteric nervous system associated with central dopaminergic impairment

Parkinson’s disease (PD) is frequently associated with gastrointestinal (GI) symptoms, mostly represented by abdominal distension, constipation and defecatory dysfunctions. Despite GI dysfunctions have a major impact on the clinical picture of PD, there is currently a lack of information on the neurochemical, pathological and functional correlates of GI dysmotility associated with PD. Moreover, there is a need of effective and safe pharmacological therapies for managing GI disturbances in PD patients. The present research project has been undertaken to investigate the relationships between PD and related GI dysfunctions by means of investigations in an animal model of PD induced by intranigral injection of 6-hydroxydopamine (6-OHDA). The use of the 6-OHDA experimental model of PD in the present program has allowed to pursue the following goals: 1) to examine the impact of central dopaminergic denervation on colonic excitatory cholinergic and tachykininergic neuromotility by means of molecular, histomorphologic and functional approaches; 2) to elucidate the role of gut inflammation in the onset and progression of colonic dysmotility associated with PD, characterizing the degree of inflammation and oxidative damage in colonic tissues, as well as identifying the immune cells involved in the production of pro-inflammatory cytokines in the gut; 3) to evaluate the impact of chronic treatment with L-DOPA plus benserazide on colonic neuromuscular activity both in control and PD animals. The results suggest that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory cholinergic neurotransmission and an enhanced tachykininergic control, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate. These motor alterations might result from the occurrence of a condition of gut inflammation associated with central intranigral denervation. The treatment with L-DOPA/BE following central dopaminergic neurodegeneration can restore colonic motility, likely through a normalization of the cholinergic enteric neurotransmission, and it can also improve the colonic inflammation associated with central dopaminergic denervation.

The tectonically-confined Firenzuola turbidite system (Miocene, Marnoso-arenacea Formation, northern Apennines, Italy): an example of facies variations related to the basin morphology

The Firenzuola turbidite system formed during a paroxysmal phase of thrust propagation, involving the upper Serravallian deposits of the Marnoso-arenacea Formation (MAF). During this phase the coeval growth of two major tectonic structures, the M. Castellaccio thrust and the Verghereto high, played a key role, causing a closure of the inner basin and a coeval shift of the depocentre to the outer basin. This work focuses on this phase of fragmentation of the MAF basin; it is based on a new detailed high-resolution stratigraphic framework, which was used to determine the timing of growth of the involved structures and their direct influence on sediment dispersal and on the lateral and vertical turbidite facies distribution. The Firenzuola turbidite system stratigraphy is characterized by the occurrence of mass-transport complexes (MTCs) and thick sandstone accumulation in the depocentral area, which passes to finer drape over the structural highs; the differentiation between these two zones increases over time and ends with the deposition of marly units over the structural highs and the emplacement of the Visignano MTC. According to the stratigraphic pattern and turbidite facies characteristics, the Firenzuola System has been split into two phases, namely Firenzuola I and Firenzuola II: the former is quite similar to the underlying deposits, while the latter shows the main fragmentation phase, testifying the progressive isolation of the inner basin and a coeval shift of the depocentre to the outer basin. The final stratigraphic and sedimentological dataset has been used to create a quantitative high-resolution 3D facies distribution using the Petrel software platform. This model allows a detailed analysis of lateral and vertical facies variations that can be exported to several reservoirs settings in hydrocarbon exploration and exploitation areas, since facies distributions and geometries of the reservoir bodies of many sub-surface turbidite basins show a significant relationship to the syndepositional structural activity, but are beyond seismic resolution.