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129 KiB

Open AccessAbstract

The Prenatal Bisphenol A Exposure Effects on Neural Signaling Activity in Male Rat Hippocampus and Its Neurobehavioral Outcomes

by Norazirah Mat Nayan, Andrean Husin, Siti Hamimah Sheikh Abd Kadir and Rosfaiizah Siran

Proceedings 2021, 75(1), 3; https://doi.org/10.3390/Cells2020-08928 - 16 Dec 2020

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Abstract

Bisphenol A (BPA) is an organic synthetic compound that is most publicized as an endocrine-disrupting chemical (EDCs) due to its remarkable effects on signaling activity via multiple steroid hormone receptors. The environmental perturbations on signaling networks such as BPA during the prenatal period may be involved in developmental disorders by anti-androgenic effects, especially on neurodevelopment leading to memory and behavior deficits when reaching adulthood. The objective of the present study is to determine the effects of prenatal BPA exposure on the relationship of synaptic plasticity markers (Synapsin I and PSD 95) with N-Methyl-D-Aspartate receptor (NMDAR) subunits (GRIN2A and GRIN2B) in neural communication networks and its neurobehavioral outcomes. Pregnant Sprague Dawley rats were orally dosed at 5 and 50 mg/kg/day with 0.5% Tween 80 in reverse osmosis water from gestational day 2 until 21 or until spontaneous delivery. The control group was exposed to the same treatment except without BPA. The male litters were raised until postnatal day 35 (PND35). At PND35, the competency of rats in learning and memory tasks was evaluated by open field, step-down passive avoidance and Morris water maze tests for six consecutive days and followed by quantification of GRIN2A, GRIN2B, PSD95 and Synapsin I using ELISA. The data obtained from the respective days show prenatal BPA exposure significantly induced anxiety-related behavior and impairment in spatial memory at the dosage BPA-treated group compared to the control group. Additionally, utero BPA exposure also significantly downregulated the expression of GRIN2A (p = 0.000), GRIN2B (p = 0.001) and PSD95 (p = 0.004) in the adult male rat hippocampus. These data suggest that the impairment in neurobehavioral performance might be involved with the inhibition of signaling pathways between synaptic plasticity markers and NMDAR subunits in the adult male rat hippocampus, leading to learning and memory deficits when reaching adulthood. Full article

(This article belongs to the Proceedings of Cell-to-Cell Metabolic Cross-Talk in Physiology and Pathology)

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970 KiB

Open AccessProceeding Paper

The Actin Cytoskeleton is a Key Element of the Apoptosome Assembly in the Developing Brain

by Igor Prudnikov, Anton Smirnov and Volodymyr Tsyvkin

Proceedings 2021, 75(1), 1; https://doi.org/10.3390/Cells2020-08923 - 16 Dec 2020

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Abstract

We investigated 2′-deoxyadenosine 5′-triphosphate (dATP) and cytochrome C-induced apoptosome formation as a source of a reliable and natural process of programmed cell death in the brain of newborn rats. We tried to find out which of the probable participants in apoptosis is responsible for the nonlinear growth of apoptosome formation at the moment of initiation of their assembly. It was found that stimulation of actin assembly by various substances, for example, Ribonuclease A (RNase A) or cations (Na⁺ or K⁺), leads to the induction of apoptosome formation. Actin polymerization inhibitor, cytochalasin D interferes with the stimulation of apoptosome assembly. We have shown for the first time that the organization of apoptosomes is directly related to the cytoskeleton and we propose to consider beta-actin as a key regulator of apoptosome formation, including it in the list of proteins that are critical for cell programmed death. Full article

(This article belongs to the Proceedings of Cell-to-Cell Metabolic Cross-Talk in Physiology and Pathology)

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258 KiB

Open AccessProceeding Paper

Apoptosomes and Proteasomes from Exosomes Generated by Human Hematopoietic Stem Cells

by Igor Prudnikov, Anton Smirnov and Volodymyr Tsyvkin

Proceedings 2021, 75(1), 2; https://doi.org/10.3390/Cells2020-08924 - 16 Dec 2020

Cited by 1 | Viewed by 1004

Abstract

The activities of two classes of neutral proteases were studied: caspases and proteasomes, which could be contained in vesicles generated by human stem cells. The formation of apoptosomes could not be induced in human mesenchymal and hematopoietic stem cells (hereinafter—MSCs and HSCs, respectively) with the participation of cytochrome C. Caspase activity was found in the culture medium and in exosomes after the tumor necrosis factor α (TNFα) supplementation only. This activity is completely inhibited by a non-substrate caspase inhibitor emricane, and is not sensitive to proteasome inhibitors. It is assumed that this activity has a membrane and intracellular location. Supplementing of TNFα cell culture leads to the generation of neutrophils and other leukocytes and the formation of apoptosomes in them, which are secreted with the exosomes and remain circulating outside the cells. Extracellular activity pertains to protein complexes of molecular weight similar to 20S proteasomes and is probably represented by apoptosomes. It is suggested that TNFα induces in HSC culture the appearance of neutrophils or the generation of other differentiated cells that are capable of apoptosis, in contrast to HSCs or MSCs. Full article

(This article belongs to the Proceedings of Cell-to-Cell Metabolic Cross-Talk in Physiology and Pathology)

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