“…Previously, prenatal exposure to CA at the doses of 20 mg/kg and 40 mg/kg undoubtedly impaired spatial learning ability . 17, 35 Therefore, we only employed the dose of 20 mg/kg in the following tests.Figure 1.ACh levels in the hippocampus and performance in the Y-maze task (A) The expression of ACh is reduced following prenatal CA exposure. #, p < .05, vs. CA (20); %, p < .05, vs. others.…”
Section: Resultsmentioning
confidence: 99%
“…15,16 Recently, spatial learning and memory defects were also observed following prenatal CA treatment. 17 The cholinergic tone can modulate ongoing hippocampal activities by enhancing the excitatory and depressing inhibitory transmissions in the hippocampus, thus increasing the excitatory output to promote neural correlate with learning processing. 18,19 However, whether the destructive effect of CA is associated with the cholinergic system is still unknown.…”
Cyanuric acid (CA) is reported to induce nephrotoxicity but its toxic effect is not fully known. Prenatal CA exposure causes neurodevelopmental deficits and abnormal behavior in spatial learning ability. Dysfunction of the acetyl-cholinergic system in neural information processing is correlated with spatial learning impairment and was found in the previous reports of CA structural analogue melamine. To further investigate the neurotoxic effects and the potential mechanism, the acetylcholine (ACh) level was detected in the rats which were exposed to CA during the whole of gestation. Local field potentials (LFPs) were recorded when rats infused with ACh or cholinergic receptor agonist into hippocampal CA3 or CA1 region were trained in the Y-maze task. We found the expression of ACh in the hippocampus was significantly reduced in dose-dependent manners. Intra-hippocampal infusion of ACh into the CA1 but not the CA3 region could effectively mitigate learning deficits induced by CA exposure. However, activation of cholinergic receptors did not rescue the learning impairments. In the LFP recording, we found that the hippocampal ACh infusions could enhance the values of phase synchronization between CA3 and CA1 regions in theta and alpha oscillations. Meanwhile, the reduction in the coupling directional index and the strength of CA3 driving CA1 in the CA-treated groups was also reversed by the ACh infusions. Our findings are consistent with the hypothesis and provide the first evidence that prenatal CA exposure induced spatial learning defect is attributed to the weakened ACh-mediated neuronal coupling and NIF in the CA3-CA1 pathway.
“…Previously, prenatal exposure to CA at the doses of 20 mg/kg and 40 mg/kg undoubtedly impaired spatial learning ability . 17, 35 Therefore, we only employed the dose of 20 mg/kg in the following tests.Figure 1.ACh levels in the hippocampus and performance in the Y-maze task (A) The expression of ACh is reduced following prenatal CA exposure. #, p < .05, vs. CA (20); %, p < .05, vs. others.…”
Section: Resultsmentioning
confidence: 99%
“…15,16 Recently, spatial learning and memory defects were also observed following prenatal CA treatment. 17 The cholinergic tone can modulate ongoing hippocampal activities by enhancing the excitatory and depressing inhibitory transmissions in the hippocampus, thus increasing the excitatory output to promote neural correlate with learning processing. 18,19 However, whether the destructive effect of CA is associated with the cholinergic system is still unknown.…”
Cyanuric acid (CA) is reported to induce nephrotoxicity but its toxic effect is not fully known. Prenatal CA exposure causes neurodevelopmental deficits and abnormal behavior in spatial learning ability. Dysfunction of the acetyl-cholinergic system in neural information processing is correlated with spatial learning impairment and was found in the previous reports of CA structural analogue melamine. To further investigate the neurotoxic effects and the potential mechanism, the acetylcholine (ACh) level was detected in the rats which were exposed to CA during the whole of gestation. Local field potentials (LFPs) were recorded when rats infused with ACh or cholinergic receptor agonist into hippocampal CA3 or CA1 region were trained in the Y-maze task. We found the expression of ACh in the hippocampus was significantly reduced in dose-dependent manners. Intra-hippocampal infusion of ACh into the CA1 but not the CA3 region could effectively mitigate learning deficits induced by CA exposure. However, activation of cholinergic receptors did not rescue the learning impairments. In the LFP recording, we found that the hippocampal ACh infusions could enhance the values of phase synchronization between CA3 and CA1 regions in theta and alpha oscillations. Meanwhile, the reduction in the coupling directional index and the strength of CA3 driving CA1 in the CA-treated groups was also reversed by the ACh infusions. Our findings are consistent with the hypothesis and provide the first evidence that prenatal CA exposure induced spatial learning defect is attributed to the weakened ACh-mediated neuronal coupling and NIF in the CA3-CA1 pathway.
“…A 30 s probe phase, during which the platform was taken out, was conducted 24 h (long-term memory test; LTM) or immediately (short-term memory test; STM) after the training phase. From the tracked swimming traces, a path proximity score was calculated by measuring the distance (cm) between the rat’s position and the platform location [ 23 , 55 ]. A distance measure was made 10 times per second and averaged across the probe test.…”
Background
Alumina nanoparticles (aluminaNPs), which are widely used in a range of daily and medical fields, have been shown to penetrate blood-brain barrier, and distribute and accumulate in different brain areas. Although oral treatment of aluminaNPs induces hippocampus-dependent learning and memory impairments, characteristic effects and exact mechanisms have not been fully elucidated. Here, male adult rats received a single bilateral infusion of aluminaNPs (10 or 20 µg/kg of body weight) into the hippocampal region, and their behavioral performance and neural function were assessed.
Results
The results indicated that the intra-hippocampus infusions at both doses of aluminaNPs did not cause spatial learning inability but memory deficit in the water maze task. This impairment was attributed to the effects of aluminaNP on memory consolidation phase through activation of proBDNF/RhoA pathway. Inhibition of the increased proBDNF by hippocampal infusions of p75NTR antagonist could effectively rescue the memory impairment. Incubation of aluminaNPs exaggerated GluN2B-dependent LTD induction with no effects on LTD expression in hippocampal slices. AluminaNP could also depress the amplitude of NMDA-GluN2B EPSCs. Meanwhile, increased reactive oxygen specie production was reduced by blocking proBDNF-p75NTR pathway in the hippocampal homogenates. Furthermore, the neuronal correlate of memory behavior was drastically weakened in the aluminaNP-infused groups. The dysfunction of synaptic and neuronal could be obviously mitigated by blocking proBDNF receptor p75NTR, implying the involvement of proBDNF signaling in aluminaNP-impaired memory process.
Conclusions
Taken together, our findings provide the first evidence that the accumulation of aluminaNPs in the hippocampus exaggeratedly activates proBDNF signaling, which leads to neural and memory impairments.
“…The concentrations were chosen from previous findings. ,, Followed by three washes with TBST buffer, the membranes were incubated with horseradish-peroxidase (HRP)-conjugated secondary goat anti-rabbit (1:1000; cat#4030-05, Southern Biotechnology Associates) or anti-mouse IgG (1:1000; cat#1030-04, Southern Biotechnology Associates) for one hour. The blots were developed using the ECL Detection Kit (CWBIO, China) in our previous findings. ,, The band intensity was measured by densitometry using Quantity One software (Bio-Rad Laboratories). All values were normalized to β-actin or β-tubulin levels within individual samples to control for differences in the total protein loaded.…”
Section: Methodsmentioning
confidence: 99%
“…The blots were developed using the ECL Detection Kit (CWBIO, China) in our previous findings. 76,97,98 The band intensity was measured by densitometry using Quantity One software (Bio-Rad Laboratories). All values were normalized to β-actin or β-tubulin levels within individual samples to control for differences in the total protein loaded.…”
Studies demonstrated that alumina nanoparticles (alumina
NPs) impair
spatial cognition and hippocampus-dependent synaptic plasticity. Although
alumina NPs accumulate in the prefrontal cortex (PFC), their effects
on PFC-mediated neuronal and cognitive function have been not yet
documented. Here, alumina NPs (10 or 20 μg/kg of body weight)
were bilaterally injected into the medial PFC (mPFC) of adult rats,
and the levels of glycogen synthase kinase 3β (GSK3β)
and the brain-derived neurotrophic factor (BDNF) were detected. The
PFC-dependent working memory task with one-minute or three-minute
delay time was conducted. Meanwhile, the neuronal correlates of working
memory performance were recorded. The specific expression of neuronal
BDNF was assessed by colabeled BDNF expression with the neuronal nuclear
antigen (NeuN). Whole-cell patch-clamp recordings were employed to
detect neuronal excitability. Intra-mPFC alumina NP infusions significantly
enhanced the expression of GSK3β but reduced the phosphorylation
of GSK3β (pGSK3β) and BDNF levels more severely at a dose
of 20 μg/kg. Alumina NPs acted in a dose-dependent manner to
impair working memory. The neuronal expression of BDNF in the 20 μg/kg
group was markedly declined compared with the 10 μg/kg group.
During the delay time, the neuronal frequency of pyramidal cells but
not interneurons was significantly weakened. Furthermore, both the
frequency and amplitude of the excitatory postsynaptic currents (EPSCs)
were descended in the mPFC slices. Additionally, the infusion of GSK3β
inhibitor SB216763 or BDNF could effectively attenuate the impairments
in neuronal correlate, neuronal activity, and working memory. From
the perspective of the identified GSK3β/BDNF pathway, these
findings demonstrated for the first time that alumina NPs exposure
can be a risk factor for prefrontal neuronal and cognitive functions.
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