TY - JOUR
T1 - Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease
AU - Blandini, F.
AU - Balestra, B.
AU - Levandis, G.
AU - Cervio, M.
AU - Greco, R.
AU - Tassorelli, C.
AU - Colucci, M.
AU - Faniglione, M.
AU - Bazzini, E.
AU - Nappi, G.
AU - Clavenzani, P.
AU - Vigneri, S.
AU - De Giorgio, R.
AU - Tonini, M.
PY - 2009/12/31
Y1 - 2009/12/31
N2 - Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.
AB - Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.
KW - Constipation
KW - Enteric neurons
KW - Gut dysfunction
KW - Neuroplasticity
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=70350773935&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350773935&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2009.10.035
DO - 10.1016/j.neulet.2009.10.035
M3 - Article
C2 - 19835930
AN - SCOPUS:70350773935
VL - 467
SP - 203
EP - 207
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -