Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

The investigations showed changes of the cystathionine γ-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese (TST) activity and gene expression in the brain, heart, liver, kidney, skeletal muscles and testes in frogs Pelophylax ridibundus, Xenopus laevis and Xenopus tropicalis in response to Pb2+, Hg2+ and Cd2+ stress. The results were analyzed jointly with changes in the expression of selected antioxidant enzymes (cytoplasmic and mitochondrial superoxide dismutase, glutathione peroxidase, catalase and thioredoxin reducatase) and with the level of malondialdehyde (a product of lipid peroxidation). The obtained results allowed for confirming the role of sulfurtransferases in the antioxidant protection of tissues exposed to heavy metal ions. Our results revealed different transcriptional responses of the investigated tissues to each of the examined heavy metals. The CTH, MPST and TST genes might be regarded as heavy metal stress-responsive. The CTH gene expression up-regulation was confirmed in the liver (Pb2+, Hg2+, Cd2+) and skeletal muscle (Hg2+), MPST in the brain (Pb2+, Hg2+), kidney (Pb2+, Cd2+), skeletal muscle (Pb2+, Hg2+,Cd2+) and TST in the brain (Pb2+) and kidney (Pb2+, Hg2+, Cd2+). Lead, mercury and cadmium toxicity was demonstrated to affect the glutathione (GSH) and cysteine levels, the concentration ratio of reduced to oxidized glutathione ([GSH]/[GSSG]) and the level of sulfane sulfur-containing compounds, which in case of enhanced reactive oxygen species generation can reveal their antioxidative properties. The present report is the first to widely describe the role of the sulfane sulfur/H2S generating enzymes and the cysteine/glutathione system in Pb2+, Hg2+ and Cd2+ stress in various frog tissues, and to explore the mechanisms mediating heavy metal-related stress.

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Acute and Chronic Exposure of Toluene Induces Genotoxicity in Different Regions of the Brain in Normal and Allergic Mouse Models

Neurotoxicity Research ◽

10.1007/s12640-019-00024-y ◽

2019 ◽

Vol 36 (4) ◽

pp. 669-678

Author(s):

Ting-Ying Laio ◽

Chih-Chun Chen ◽

Han-Hsing Tsou ◽

Tsung-Yun Liu ◽

Hsiang-Tsui Wang

Keyword(s):

Mouse Models ◽

Chronic Exposure ◽

Acute And Chronic Exposure ◽

The Brain ◽

Allergic Mouse

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Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

Journal of Neurophysiology ◽

10.1152/jn.00476.2006 ◽

2006 ◽

Vol 96 (5) ◽

pp. 2265-2273 ◽

Cited By ~ 30

Author(s):

Radi Masri ◽

Jason C. Trageser ◽

Tatiana Bezdudnaya ◽

Ying Li ◽

Asaf Keller

Keyword(s):

Brain Stem ◽

Cholinergic System ◽

Somatosensory System ◽

Zona Incerta ◽

State Dependent ◽

Presynaptic Site ◽

Behavioral States ◽

Flow Of Information ◽

The Brain

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep–wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

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Cerium(iv) oxide nanoparticles induce sublethal changes in honeybees after chronic exposure

Environmental Science Nano ◽

10.1039/c7en00596b ◽

2017 ◽

Vol 4 (12) ◽

pp. 2297-2310 ◽

Cited By ~ 6

Author(s):

Monika Kos ◽

Anita Jemec Kokalj ◽

Gordana Glavan ◽

Gregor Marolt ◽

Primož Zidar ◽

...

Keyword(s):

Cholinergic System ◽

Chronic Exposure ◽

Physiological Responses ◽

Oral Exposure ◽

Oxide Nanoparticles

Oral exposure to up to 500 mg L−1 nCeO2 was sublethal for honeybees but altered the cholinergic system and induced other physiological responses.

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A study on blood flow and glucose consumption for the mapping of the brain cholinergic system in Alzheimer's disease

NeuroImage ◽

10.1016/s1053-8119(96)80573-8 ◽

1996 ◽

Vol 3 (3) ◽

pp. S571

Author(s):

J Blin ◽

A Ivanoiu ◽

A Bol ◽

A De Volder ◽

A Coppens ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cholinergic System ◽

Glucose Consumption ◽

The Brain

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Chronic Excess of Non-Aromatizable Androgens From Puberty Does Not Drive a Neuroendocrine Phenotype Observed in Other Preclinical Rodent Models of PCOS

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1086 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A533-A534

Author(s):

Chris Coyle ◽

Amy Ruddenklau ◽

Mel Prescott ◽

Kirsty A Walters ◽

Rebecca Elaine Campbell

Keyword(s):

Chronic Exposure ◽

Fluorescent Protein ◽

Polycystic Ovary ◽

Prenatal Development ◽

Reproductive Age ◽

Androgen Excess ◽

Gabaergic Innervation ◽

Lh Pulsatility ◽

Gnrh Neurons ◽

The Brain

Abstract Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility in women of reproductive age, characterised by androgen excess, polycystic appearance of the ovary and irregular menstruation. PCOS is also frequently associated with metabolic abnormalities, including increased adiposity and insulin resistance. The origins of PCOS are unknown, however recent findings in animal models strongly implicate androgen signalling in the brain in the development of PCOS pathophysiology. Exposure to androgen excess, either acutely during prenatal development or chronically from a peripubertal timepoint, can drive the development of PCOS-like features in adulthood. Prenatally androgenized (PNA) mice exhibit the cardinal reproductive features of PCOS and increased luteinizing hormone (LH) pulse frequency. This phenotype is associated with increased GABAergic innervation of gonadotropin-releasing hormone (GnRH) neurons, postulated to drive elevated GnRH/LH release and downstream effects. Chronic exposure to di-hydrotestosterone (DHT) from 3 weeks of age drives both reproductive and metabolic PCOS-like features that are ameliorated by selective AR loss from the brain. Here, we aimed to determine whether chronic exposure to DHT drives a similar increase in LH pulsatility and elevated GABAergic innervation to GnRH neurons as seen following prenatal exposure to androgen excess. GnRH-green fluorescent protein (GFP) female mice received either DHT or blank capsules for 90 days from postnatal day (PND) 21 (N = 6-7/group). Serial tail tip blood sampling was used to measure pulsatile LH and fixed brains were collected and immunolabelled for vesicular GABA transporter (VGAT) to assess putative GABAergic terminals associated with GFP-labelled GnRH neurons. Chronic androgen excess from the peripubertal period resulted in acyclicity and increased body weight as expected. However, LH pulsatility was not different between DHT-treated females and controls. Similarly, the density of VGAT appositions to GnRH neurons was not different between groups. Therefore, the programmed changes in the GnRH neuronal network and hyperactive LH secretion that result from prenatal androgen excess are not affected by chronic DHT exposure initiated at 3 weeks of age. These findings suggest that unique central mechanisms are involved in the reproductive impairments driven by exposure to androgen excess at different developmental stages.

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