Changes in the Population Size of Calbindin D-28k-Immunoreactive Enteric Neurons in the Porcine Caecum under the Influence of Bisphenol A: A Preliminary Study

Calbindin D-28k (CB) is a calcium-binding protein widely distributed in living organisms that may act as a calcium buffer and sensory protein. CB is present in the enteric nervous system (ENS) situated in the gastrointestinal tract, which controls the majority of activities of the stomach and intestine. The influence of various doses of bisphenol A (BPA)—a chemical compound widely used in plastics production—on the number and distribution of CB-positive enteric neuronal cells in the porcine caecum was investigated with an immunofluorescence technique. The obtained results showed that low dosages of BPA resulted in an increase in the number of CB-positive neuronal cells in the myenteric (MP) and inner submucous (ISP) plexuses, whereas it did not alter the number of such neuronal cells in the outer submucous plexus (OSP). High dosages of BPA caused the increase in the amount of CB-positive perikarya in all the above-mentioned kinds of the caecal neuronal plexuses. These observations strongly suggest that CB in the ENS participates in the processes connected with the toxic activity of BPA. Most likely, the changes noted in this experiment result from the adaptive and protective properties of CB.

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The T2 Toxin Produced by Fusarium spp. Impacts Porcine Duodenal Nitric Oxide Synthase (nNOS)-Positive Nervous Structures—The Preliminary Study

International Journal of Molecular Sciences ◽

10.3390/ijms21145118 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5118

Author(s):

Andrzej Rychlik ◽

Slawomir Gonkowski ◽

Ewa Kaczmar ◽

Kazimierz Obremski ◽

Jaroslaw Calka ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Enteric Neurons ◽

Fusarium Spp ◽

Internal Organs ◽

Preliminary Study ◽

Living Organisms ◽

T2 Toxin ◽

Oxide Synthase

T2 toxin synthetized by Fusarium spp. negatively affects various internal organs and systems, including the digestive tract and the immune, endocrine, and nervous systems. However, knowledge about the effects of T2 on the enteric nervous system (ENS) is still incomplete. Therefore, during the present experiment, the influence of T2 toxin with a dose of 12 µg/kg body weight (b.w.)/per day on the number of enteric nervous structures immunoreactive to neuronal isoform nitric oxide synthase (nNOS—used here as a marker of nitrergic neurons) in the porcine duodenum was studied using the double immunofluorescence method. Under physiological conditions, nNOS-positive neurons amounted to 38.28 ± 1.147%, 38.39 ± 1.244%, and 35.34 ± 1.151 of all enteric neurons in the myenteric (MP), outer submucous (OSP), and inner submucous (ISP) plexuses, respectively. After administration of T2 toxin, an increase in the number of these neurons was observed in all types of the enteric plexuses and nNOS-positive cells reached 46.20 ± 1.453% in the MP, 45.39 ± 0.488% in the OSP, and 44.07 ± 0.308% in the ISP. However, in the present study, the influence of T2 toxin on the intramucosal and intramuscular nNOS-positive nerves was not observed. The results obtained in the present study indicate that even low doses of T2 toxin are not neutral for living organisms because they may change the neurochemical characterization of the enteric neurons.

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The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine

International Journal of Molecular Sciences ◽

10.3390/ijms221910308 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10308

Author(s):

Krystyna Makowska ◽

Kamila Szymańska ◽

Jarosław Całka ◽

Sławomir Gonkowski

Keyword(s):

Bisphenol A ◽

Enteric Neurons ◽

Neuregulin 1 ◽

Enteric Plexus ◽

Other Substances ◽

Intestinal Functions ◽

Living Organisms ◽

Oxide Synthase ◽

The Impact ◽

Active Substances

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.

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Changes Caused by Low Doses of Bisphenol A (BPA) in the Neuro-Chemistry of Nerves Located in the Porcine Heart

Animals ◽

10.3390/ani11030780 ◽

2021 ◽

Vol 11 (3) ◽

pp. 780

Author(s):

Krystyna Makowska ◽

Slawomir Gonkowski

Keyword(s):

Bisphenol A ◽

Endocrine Disruptor ◽

Sympathetic Innervation ◽

Daily Intake ◽

Everyday Objects ◽

Living Organisms ◽

The Impact ◽

Heart Wall ◽

Cholinergic Structures

Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.

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Oral Amylin Treatment Reduces the Pathological Cascade of Alzheimer’s Disease in a Mouse Model

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/15333175211012867 ◽

2021 ◽

Vol 36 ◽

pp. 153331752110128

Author(s):

Hana Na ◽

Hua Tian ◽

Zhengrong Zhang ◽

Qiang Li ◽

Jack B. Yang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Calcium Binding ◽

Oral Delivery ◽

Amyloid Β ◽

Enteric Neurons ◽

Cyclin Dependent Kinase ◽

Receptor Activity Modifying Proteins ◽

The Brain ◽

Cyclin Dependent Kinase 5

Intraperitoneal injection of amylin or its analog reduces Alzheimer’s disease (AD) pathology in the brains. However, self-injecting amylin analogs is difficult for patients due to cognitive deficits. This work aims to study the effects of amylin on the brain could be achieved by oral delivery as some study reported that amylin receptor may be present in the gastrointestinal tract. A 6-week course of oral amylin treatment reduced components of AD pathology, including the levels of amyloid-β, phosphorylated tau, and ionized calcium binding adaptor molecule 1. The treatment reduced active forms of cyclin-dependent kinase 5. Oral amylin treatment led to improvements in social deficit in AD mouse. Using immunofluorescence, we observed the amylin receptor complexed with the calcitonin receptor and receptor activity-modifying proteins in the enteric neurons. The study suggests the potential of the oral delivery of amylin analogs for the treatment of AD and other neurodegenerative diseases through enteric neurons.

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Electrical tuning and transduction in short hair cells of the chicken auditory papilla

Journal of Neurophysiology ◽

10.1152/jn.01028.2012 ◽

2013 ◽

Vol 109 (8) ◽

pp. 2007-2020 ◽

Cited By ~ 17

Author(s):

Xiaodong Tan ◽

Maryline Beurg ◽

Carole Hackney ◽

Shanthini Mahendrasingam ◽

Robert Fettiplace

Keyword(s):

Hair Cells ◽

Calcium Binding ◽

Outer Hair Cells ◽

Basilar Papilla ◽

Resting Potential ◽

Auditory Nerve Fiber ◽

Buffer Concentration ◽

Short Hair ◽

Open Probability ◽

Calbindin D

The avian auditory papilla contains two classes of sensory receptor, tall hair cells (THCs) and short hair cells (SHCs), the latter analogous to mammalian outer hair cells with large efferent but sparse afferent innervation. Little is known about the tuning, transduction, or electrical properties of SHCs. To address this problem, we made patch-clamp recordings from hair cells in an isolated chicken basilar papilla preparation at 33°C. We found that SHCs are electrically tuned by a Ca2+-activated K+ current, their resonant frequency varying along the papilla in tandem with that of the THCs, which also exhibit electrical tuning. The tonotopic map for THCs was similar to maps previously described from auditory nerve fiber measurements. SHCs also possess an A-type K+ current, but electrical tuning was observed only at resting potentials positive to −45 mV, where the A current is inactivated. We predict that the resting potential in vivo is approximately −40 mV, depolarized by a standing inward current through mechanotransducer (MT) channels having a resting open probability of ∼0.26. The resting open probability stems from a low endolymphatic Ca2+ concentration (0.24 mM) and a high intracellular mobile Ca2+ buffer concentration, estimated from perforated-patch recordings as equivalent to 0.5 mM BAPTA. The high buffer concentration was confirmed by quantifying parvalbumin-3 and calbindin D-28K with calibrated postembedding immunogold labeling, demonstrating >1 mM calcium-binding sites. Both proteins displayed an apex-to-base gradient matching that in the MT current amplitude, which increased exponentially along the papilla. Stereociliary bundles also labeled heavily with antibodies against the Ca2+ pump isoform PMCA2a.

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Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

Journal of Endocrinology ◽

10.1677/joe.0.1640067 ◽

2000 ◽

Vol 164 (1) ◽

pp. 67-76 ◽

Cited By ~ 14

Author(s):

K Hamilton ◽

M Tein ◽

J Glazier ◽

EB Mawer ◽

JL Berry ◽

...

Keyword(s):

Calcium Binding ◽

Plasma Concentrations ◽

Diabetic Pregnancy ◽

Mrna Abundance ◽

Pregnant Rats ◽

Altered Expression ◽

Dihydroxyvitamin D ◽

Igf I ◽

Calbindin D ◽

Plasma Oestradiol

Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations. Three rat groups were studied; control (CP), streptozotocin-induced diabetic (DP), and insulin-treated diabetic (DPI) pregnant rats. Calbindin-D(9K) and calbindin-D(28K) mRNA abundance in placenta and maternal kidney were measured at days 7, 15, 18 and 21 of gestation, together with serum or plasma concentrations of 1,25 dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)), parathyroid hormone (PTH), PTH-related protein (PTHrP), calcitonin, oestradiol and IGF-I. An increase in placental calbindin-D(9K) mRNA abundance between days 18 and 21 in CP and DPI rats was severely blunted in the DP rats. In contrast, renal calbindin-D(28K) mRNA abundance was greater at days 7, 15 and 18 in DP compared with CP rats, as was calbindin-D(9K) at day 18. Calcitonin concentrations showed no differences between the groups, and both PTH and IGF-I were reduced over the first half of gestation, unlike the calbindins. In contrast, the concentrations of PTHrP and 1,25(OH)(2)D(3) were reduced at term in the DP group compared with the other two groups. Plasma oestradiol concentrations were lower in DP than in CP rats at days 7, 15 and 18, and most striking was the absence in DP rats of the peak of oestradiol seen at day 18 in CP rats. Despite the similarity between changes in placental calbindin mRNA and 1,25(OH)(2)D(3), previous work has shown placental calbindin-D(9K) regulation to be vitamin-D-independent. These studies produce suggestive evidence, therefore, that PTHrP and oestradiol may be involved in the altered calbindin-D expression by kidney and placenta in rat diabetic pregnancy.

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Bisphenol A (BPA) Affects the Enteric Nervous System in the Porcine Stomach

Animals ◽

10.3390/ani10122445 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2445

Author(s):

Krystyna Makowska ◽

Sławomir Gonkowski

Keyword(s):

Nervous System ◽

Bisphenol A ◽

Enteric Nervous System ◽

Gastric Wall ◽

Cholinergic Neurons ◽

Double Immunofluorescence ◽

Adaptive Processes ◽

Living Organisms ◽

The Impact ◽

Myenteric Ganglia

Bisphenol A (BPA) is widely utilized in plastic production process all over the world. Previous studies have shown that BPA, with its similarity to estrogen, may negatively affect living organisms. It is acknowledged that BPA distorts the activity of multiple internal systems, including the nervous, reproductive, urinary, and endocrine systems. BPA also affects the gastrointestinal tract and enteric nervous system (ENS), which is placed throughout the wall from the esophagus to the rectum. Contrary to the intestine, the influence of BPA on the ENS in the stomach is still little known. This study, performed using the double immunofluorescence method, has revealed that BPA affects the number of nervous structures in the porcine gastric wall immunoreactive to vesicular acetylcholine transporter (VAChT, a marker of cholinergic neurons), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL) and cocaine- and amphetamine-regulated transcript peptide (CART). The character and severity of noted alterations depended on the part of the ENS, the BPA dose, and the type of neuronal substance. Administration of BPA resulted in an increase in the number of nervous structures containing SP, GAL, and/or CART, and a decrease in the number of cholinergic neurons in all parts of the gastric wall. The number of VIP-positive nervous structures increased in the enteric myenteric ganglia, along with the muscular and mucosal layers, whilst it decreased in the submucous ganglia. The exact mechanism of noted changes was not absolutely obvious, but they were probably related to the neuroprotective and adaptive processes constituting the response to the impact of BPA.

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