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

Abstract

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.

Pathophysiological Studies of Monoaminergic Neurotransmission Systems in Valproic Acid-Induced Model of Autism Spectrum Disorder

“…The dorsal and median raphe nuclei may differ in vulnerabilities to VPA treatments. Reduced serotonin receptors have also been found in the hippocampus [93]. In other brain regions, alterations in 5-HT levels are more consistent.…”

“…At the behavioral level, consistent behavioral phenotypes have been found along with catecholaminergic abnormalities in VPA-treated rodents, including reduced social behaviors, increased repetitive, depressive and anxious behaviors, and impaired memory [14,66,84,86,93,99,131,133,134,138]. Impaired cognitive flexibility and temporal processing have also been observed in VPA-treated rodents, implicating abnormal functions of the prefrontal cortex [131,132].…”

“…By contrast, decreased DA levels were found in the hippocampus, midbrain, and serum of VPA-treated animals [86,99]. The variations in the changes in DA levels in different brain regions may result from the differences in DA turnover and/or the expression of DA-related signaling molecules in different brain regions, including DA receptor, acetylation of DAT, and phosphorylation of DARPP-32 in response to social stimulus [66,93,[133][134][135]. Along this line, an interesting question is whether the dopaminergic systems may be affected by the external environment.…”

A facile approach to create sensitive and selective Cu(ii) sensors on carbon fiber microelectrodes

“…Moreover, studies have revealed different Cu content in different regions of the brain. 15,16 This is important because the hippocampus and cortex, for example, are more susceptible to plaque formation. 17 Copper quantitation in biological samples is commonly accomplished by separations and spectroscopic techniques with high sensitivity.…”

“…Moreover, studies have revealed different Cu content in different regions of the brain. 15,16 This is important because the hippocampus and cortex, for example, are more susceptible to plaque formation. 17…”