The Endocrine Disruptor Bisphenol A (BPA) Affects the Enteric Neurons Immunoreactive to Neuregulin 1 (NRG1) in the Enteric Nervous System of the Porcine Large Intestine.

Kamila Szymańska,Sławomir Gonkowski,Krystyna Makowska,Jarosław Całka

doi:10.3390/ijms21228743

Kamila Szymańska, Sławomir Gonkowski + Show 2 more

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https://doi.org/10.3390/ijms21228743

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Abstract

The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin 1 (NRG1), a factor known to be involved in the assurance of normal development of the nervous system. During the study, made up using the double immunofluorescence technique, the presence of NRG1 in the ENS of the selected segment of porcine large intestine (caecum, ascending and descending colon) was observed in physiological conditions, as well as under the impact of low and high doses of bisphenol A (BPA) which is commonly used in the production of plastics. In control animals in all types of the enteric plexuses, the percentage of NRG1-positive neurons oscillated around 20% of all neurons. The administration of BPA caused an increase in the number of NRG1-positive neurons in all types of the enteric plexuses and in all segments of the large intestine studied. The most visible changes were noted in the inner submucous plexus of the ascending colon, where in animals treated with high doses of BPA, the percentage of NRG1-positive neurons amounted to above 45% of all neuronal cells. The mechanisms of observed changes are not entirely clear, but probably result from neurotoxic, neurodegenerative and/or proinflammatory activity of BPA and are protective and adaptive in nature.

Highlights

Neuregulin 1 (NRG1) was described for the first time in 1992 as a 44-kD glycoprotein purified from the medium of a human breast tumor cell line [1]
Neuronal cells immunoreactive to NRG1 were observed in all types of enteric plexuses of all segments of the large intestine studied, both in control animals and in pigs treated with bisphenol A (BPA) (Table 2, Figures 2–4)
The presence of NRG1 was not observed in the nerve fibers located within the intestinal wall, as well as in cells immunonegative to protein gene product 9.5 (PGP 9.5- used as a panneuronal marker) located in the enteric ganglia

Summary

Introduction

Neuregulin 1 (NRG1) was described for the first time in 1992 as a 44-kD glycoprotein purified from the medium of a human breast tumor cell line [1]. As regards the nervous system, the majority of previous studies concern distribution and functions of NRG1 in the central nervous system. This substance has been found in the brain of various animal species, including, among others, human [6], rat [7], mouse [8] and goose [9]. It is known that NRG1 in the central nervous system is involved in hypothalamic control of sexual maturation in rats [10], participates in mechanisms connected with oligodendrocytes survivability and differentiation in mice [11] and regulates the higher nervous functions in rats (including memory and learning) [12]

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