Distribution and characterization of α-syn immunoreactivity in the enteric nervous system of human small intestine

The enteric nervous system (ENS) is a network of neurons and glia found in the gut wall which controls gastrointestinal function independently from the central nervous system. Alpha-synuclein (α-syn) is a 140-amino acid protein widely expressed in presynaptic nerve terminals and its structural alterations plays an important role in the pathogenesis of neurodegenerative diseases as Parkinson’s disease (PD). PD is characterized by α-syn deposition into neuronal cell bodies and fibers, which leads to the formation of Lewy bodies and Lewy neurites. Although originally described in the brain, aggregated α-synuclein is also been found in the peripheral nerves including the enteric nervous system of PD patients. PD is frequently associated with gastrointestinal symptoms and recent studies have raised the possibility that the ENS is one of the early sites of alpha-synuclein pathology in PD, indeed gastrointestinal symptoms often appear in patients before other neurological signs. Our aim is to evidence and characterize α-syn immunoreactive (ir) structures, using the main enteric neurotransmitters, in human normal ENS. Surgical specimens of proximal jejunum were collected from patients submitted to pancreaticoduodenectomy and intestinal sections underwent immunohistochemical procedure using monoclonal or polyclonal antibody for α-syn, choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), substance P (SP) and vasoactive intestinal polypeptide (VIP). α-syn ir was widespread detected in all layers of intestinal wall, and co-distributed with major enteric neurotransmitters. Numerous α-syn ir fibers and some α-syn ir neuronal bodies were found in the ganglia of myenteric plexus, and in some of these α-syn and ChAT are colocalized. Our preliminary observations on the presence and characterization of α-syn immunoreactivity in the human ENS may elucidate its physiological role, and could help to understand how its structural alterations could contribute in the pathogenesis of neurodegenerative disease.