Zinc and Copper Brain Levels and Expression of Neurotransmitter Receptors in Two Rat ASD Models

Zinc and copper are important trace elements necessary for the proper functioning of neurons. Impaired zinc and/or copper metabolism and signaling are implicated in many brain diseases, including autism (ASD). In our studies, autistic-like behavior in rat offsprings was induced by application to pregnant mothers valproic acid or thalidomide. Zinc and copper contents were measured in serum and brain structures: hippocampus, cerebral cortex, and cerebellum. Our research shows no interconnections in the particular metal concentrations measured in autistic animal brains and their sera. Based on patient researches, we studied 26 genes belonging to disturbed neurotransmitter pathways. In the same brain regions, we examined the expression of genes encoding proteins of cholinergic, adrenergic, serotonin, and dopamine receptors. In both rats’ ASD models, 17 out of the tested gene expression were decreased. In the cerebellum and cerebral cortex, expression of genes encoding cholinergic, adrenergic, and dopaminergic receptors decreased, whereas in the hippocampus only expression of serotoninergic receptors genes was downregulated. The changes in metals content observed in the rat brain can be secondary phenomena, perhaps elements of mechanisms that compensate for neurotransmission dysfunctions.

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Expression of Genes Encoding Serotonin Receptors and SERT in Various Brain Structures of Stressed Rats after Chronic Exposure to Ultrasound

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-014-2338-y ◽

2014 ◽

Vol 156 (3) ◽

pp. 317-319 ◽

Cited By ~ 4

Author(s):

A. Yu. Morozova ◽

E. A. Zubkov ◽

F. A. Koshkin ◽

Z. I. Storozheva ◽

V. P. Chekhonin

Keyword(s):

Serotonin Receptors ◽

Chronic Exposure ◽

Brain Structures ◽

Expression Of Genes ◽

Genes Encoding

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The effect of silver ions on copper metabolism and expression of genes encoding copper transport proteins in rat liver

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672908010067 ◽

2008 ◽

Vol 418 (1) ◽

pp. 24-27 ◽

Cited By ~ 7

Author(s):

S. A. Klotchenko ◽

N. V. Tsymbalenko ◽

K. V. Solov’ev ◽

A. N. Skvortsov ◽

E. A. Zatulovskii ◽

...

Keyword(s):

Rat Liver ◽

Copper Metabolism ◽

Silver Ions ◽

Transport Proteins ◽

Copper Transport ◽

Expression Of Genes ◽

Genes Encoding

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Rapid Efflux of Lactate from Cerebral Cortex during K+-Induced Spreading Cortical Depression

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199904000-00004 ◽

1999 ◽

Vol 19 (4) ◽

pp. 380-392 ◽

Cited By ~ 74

Author(s):

Nancy F. Cruz ◽

Keiji Adachi ◽

Gerald A. Dienel

Keyword(s):

Cerebral Cortex ◽

Steady State ◽

Brain Structures ◽

Brain Regions ◽

Uniform Pattern ◽

Spreading Cortical Depression ◽

Cortical Depression ◽

Rapid Transport ◽

Glucose Metabolites ◽

Derivatives Of

Rapid transport of lactate from activated brain regions to blood, perhaps reflecting enhanced metabolite trafficking, would prevent local trapping of labeled metabolites of [6-14C]glucose and cause underestimation of calculated CMRglc. Because the identities of glucose metabolites lost from activated structures and major routes of their removal are not known, arteriovenous differences across brains of conscious normoxic rats for derivatives of [6-14C]glucose were determined under steady-state conditions in blood during K+-induced spreading cortical depression. Lactate was identified as the major labeled product lost from brain. Its entry to blood was detected within 2 minutes after a pulse of [6-14C]glucose, and it accounted for 96% of the 14C lost from brain within approximately 8 minutes. Lactate efflux corresponded to 20% of glucose influx, but accounted for only half the magnitude of underestimation of CMRglc when [14C]glucose is the tracer, suggesting extensive [14C]lactate trafficking within brain. [14C]Lactate spreading within brain is consistent with (1) relatively uniform pattern labeling of K+-treated cerebral cortex by [6-14C]glucose contrasting heterogeneous labeling by [14C]deoxyglucose, and (2) transport of 14C-labeled lactate and inulin up to 1.5 and 2.4 mm, respectively, within 10 minutes. Thus, newly synthesized lactate exported from activated cells rapidly flows to blood and probably other brain structures.

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Messenger RNA levels of enzymes involved in glycerolipid synthesis in the brain of the mouse and its alterations in Agpat2-/- and db/db mice

10.21203/rs.3.rs-128675/v1 ◽

2020 ◽

Author(s):

Lila Gonzalez-Hodar ◽

Anil K. Agarwal ◽

Víctor Cortés

Keyword(s):

Mouse Brain ◽

Messenger Rna ◽

Brain Regions ◽

Mrna Levels ◽

Expression Of Genes ◽

Genes Encoding ◽

Glycerolipid Synthesis ◽

Altered Gene ◽

The Brain

Abstract Background and Aims: Expression of genes encoding enzymes involved in glycerolipid and monoacylglycerol pathways in specific brain regions is poorly known and their alterations in insulin resistance (IR) and type 2 diabetes (T2D) remain unreported. We determined the mRNA levels of enzymes involved in glycerolipid synthesis in specific regions of the mouse brain and their changes in two models of severe IR, the lipodystrophic Agpat2−/− and the obese Leprdb/db mice. Methods Cerebral cortex, hypothalamus, hippocampus and cerebellum were dissected from adult Agpat2−/− mice, Leprdb/db mice and their respective wild type littermates. Total RNA was isolated and the relative mRNA abundance of enzymes was determined by RT-qPCR. Results GPAT1, AGPAT1-4, LIPIN1/2, DGAT1/2 and MOGAT1 mRNAs were detected in all studied brain regions, whereas GPAT2, LIPIN3 and MOGAT2 were undetectable. Abundance of GPAT1, AGPAT1, AGPAT2, AGPAT4, LIPIN1, and MOGAT1, was higher in the hypothalamus. AGPAT3 and DGAT1 were higher in cortex and cerebellum, and LIPIN2 and DGAT2 were higher in cortex and hippocampus. In Agpat2−/− mice, LIPIN1 levels were increased in all the brain regions. By contrast, GPAT1 and AGPAT4 in hypothalamus, AGPAT3 in hippocampus and hypothalamus, and MOGAT1 in cortex, hypothalamus and cerebellum were lower in Agpat2−/− mice. Leprdb/db mice showed fewer and milder changes, with increased levels of GPAT1 and LIPIN1 in cerebellum, and AGPAT3 in hypothalamus. Conclusions Enzymes involved in glycerolipids synthesis are differentially expressed across regions of the mouse brain and IR and T2D determine altered gene expression of these enzymes in the mouse brain.

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Chronic Exposure to Fluoride Affects GSH Level and NOX4 Expression in Rat Model of This Element of Neurotoxicity

Biomolecules ◽

10.3390/biom10030422 ◽

2020 ◽

Vol 10 (3) ◽

pp. 422 ◽

Cited By ~ 1

Author(s):

Karolina Dec ◽

Agnieszka Łukomska ◽

Karolina Skonieczna-Żydecka ◽

Karolina Jakubczyk ◽

Maciej Tarnowski ◽

...

Keyword(s):

Oxidative Stress ◽

Prefrontal Cortex ◽

Neuronal Loss ◽

Brain Structures ◽

Neural Cells ◽

Nadph Oxidase 4 ◽

Expression Of Genes ◽

Genes Encoding ◽

Total Antioxidant ◽

Blood Brain Barrier Damage

Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT–PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood–brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines.

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Messenger RNA levels of enzymes involved in glycerolipid synthesis in the brain of the mouse and its alterations in Agpat2-/- and db/db mice

10.1101/2020.04.02.021808 ◽

2020 ◽

Author(s):

Lila González-Hódar ◽

Anil K. Agarwal ◽

Víctor Cortés

Keyword(s):

Mouse Brain ◽

Messenger Rna ◽

Brain Regions ◽

Mrna Levels ◽

Expression Of Genes ◽

Genes Encoding ◽

Glycerolipid Synthesis ◽

Altered Gene ◽

The Brain

AbstractAimsExpression of genes encoding enzymes involved in glycerolipid and monoacylglycerol pathways in specific brain regions is poorly known and its impact in insulin resistance (IR) and type 2 diabetes (T2D) in the brain remains unreported. We determined mRNA levels of enzymes involved in glycerolipid synthesis in different regions of the mouse brain and evaluated their changes in two models of IR and T2D, the Agpat2-/- and Leprdb/db mice.MethodsCerebral cortex, hypothalamus, hippocampus and cerebellum were dissected from adult Agpat2-/- mice, Leprdb/db mice and their respective wild type littermates. Total RNA was isolated and mRNA abundance was measured by RT-qPCR.Key findingsGPAT1, AGPAT1-4, LIPIN1/2, DGAT1/2 and MOGAT1 mRNAs were detected in all studied brain regions, whereas GPAT2, LIPIN3 and MOGAT2 were undetectable. Abundance of AGPATs, LIPIN1 and DGAT1, was higher in cerebellum and hypothalamus. LIPIN2 and MOGAT1 levels were higher in hypothalamus, and DGAT2 was higher in cortex and hypothalamus. In Agpat2-/- mice, LIPIN1 levels were increased in all the brain regions. By contrast, GPAT1 in cortex and hypothalamus, AGPAT3 in hippocampus and hypothalamus, AGPAT4 in hypothalamus, and MOGAT1 in cortex, hypothalamus and cerebellum were lower in Agpat2-/- mice. Leprdb/db mice showed fewer and milder changes, with increased levels of GPAT1 and LIPIN1 in cerebellum, and AGPAT3 in hypothalamus.Conclusions and SignificanceEnzymes of glycerolipids synthesis are differentially expressed across regions of the mouse brain. Two mouse models of IR and T2D have altered gene expression of glycerolipid enzymes in the brain.

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