Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels

Lara-Valderrábano, Leonardo; Rocha, Luísa; Galván, Emilio J.

doi:10.1016/j.neuro.2016.09.019

Cited by 16 publications

(6 citation statements)

References 43 publications

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“…The fast‐inactivating sodium current ( I Na ) was isolated as previously described (Herrera‐López & Galván, 2018; Lara‐Valderrábano et al, 2016). Cells were held at −70 mV and voltage commands from −80 to +60 mV (10 mV step increase, 20 ms) were applied.…”

Section: Resultsmentioning

confidence: 99%

Activation of D1/D5 receptors ameliorates decreased intrinsic excitability of hippocampal neurons induced by neonatal blockade of N‐methyl‐d‐aspartate receptors

Griego

Hernández-Frausto

Márquez

et al. 2022

British J Pharmacology

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Section: Resultsmentioning

confidence: 99%

Activation of D1/D5 receptors ameliorates decreased intrinsic excitability of hippocampal neurons induced by neonatal blockade of N‐methyl‐d‐aspartate receptors

Griego

Hernández-Frausto

Márquez

et al. 2022

British J Pharmacology

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“…Subsequently, we sought to determine whether activation of HCA1 modulates the fast voltage‐gated sodium current ( I Na ) underlying the action potential spike as suggested by the phase plot analysis. The somatic I Na was isolated as previously described for acute slices (Lara‐Valderrábano, Rocha, & Galván, ). To reduce the contribution of axonal sodium currents near the somatic clamp, a depolarizing pulse was applied as previously described (Milescu et al, ).…”

Section: Resultsmentioning

confidence: 99%

Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1

Herrera-López

Galván

2018

Hippocampus

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In addition to its prominent role as an energetic substrate in the brain, lactate is emerging as a signaling molecule capable of controlling neuronal excitability. The finding that the lactate-activated receptor (hydroxycarboxylic acid receptor 1; HCA1) is widely expressed in the brain opened up the possibility that lactate exerts modulation of neuronal activity via a transmembranal receptor-linked mechanism. Here, we show that lactate causes biphasic modulation of the intrinsic excitability of CA1 pyramidal cells. In the low millimolar range, lactate or the HCA1 agonist 3,5-DHBA reduced the input resistance and membrane time constant. In addition, activation of HCA1 significantly blocked the fast inactivating sodium current and increased the delay from inactivation to a conducting state of the sodium channel. As the observed actions occurred in the presence of 4-CIN, a blocker of the neuronal monocarboxylate transporter, the possibility that lactate acted via neuronal metabolism is unlikely. Consistently, modulation of the intrinsic excitability was abolished when CA1 pyramidal cells were dialyzed with pertussis toxin, indicating the dependency of a G -protein-coupled receptor. The activation of HCA1 appears to serve as a restraining mechanism during enhanced network activity and may function as a negative feedback for the astrocytic production of lactate.

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“…It is confirmed that embryonic exposure to PrP triggered anxiety-like neurobehavioral response in zebrafish, which is correlated with oxidative-stress-induced apoptosis in the head of the larvae [ 27 ]. Nevertheless, PrP was suggested to reduce the excitability of hippocampal neurons in rats [ 62 ], and to have anticonvulsant effects on pentylenetetrazol-induced seizures in zebrafish [ 63 ], demonstrating the potential for use in anticonvulsant drugs. In this study, cell cavitation, cytomorphosis and blurred cell boundaries were found in the brain of mosquitofish, the deleterious effects of PrP on the physiological function of brain should be noteworthy to illuminate the safety and toxicity mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Endocrine Disruption of Propylparaben in the Male Mosquitofish (Gambusia affinis): Tissue Injuries and Abnormal Gene Expressions of Hypothalamic-Pituitary-Gonadal-Liver Axis

Song

et al. 2023

IJERPH

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Propylparaben (PrP) is a widely used preservative that is constantly detected in aquatic environments and poses a potential threat to aquatic ecosystems. In the present work, adult male mosquitofish were acutely (4d) and chronically (32d) exposed to environmentally and humanly realistic concentrations of PrP (0, 0.15, 6.00 and 240 μg/L), aimed to investigate the toxic effects, endocrine disruption and possible mechanisms of PrP. Histological analysis showed time- and dose-dependent manners in the morphological injuries of brain, liver and testes. Histopathological alterations in the liver were found in 4d and severe damage was identified in 32d, including hepatic sinus dilatation, cytoplasmic vacuolation, cytolysis and nuclear aggregation. Tissue impairments in the brain and testes were detected in 32d; cell cavitation, cytomorphosis and blurred cell boundaries appeared in the brain, while the testes lesions contained spermatogenic cell lesion, decreased mature seminal vesicle, sperm cells gathering, seminiferous tubules disorder and dilated intercellular space. Furthermore, delayed spermatogenesis had occurred. The transcriptional changes of 19 genes along the hypothalamus–pituitary–gonadal–liver (HPGL) axis were investigated across the three organs. The disrupted expression of genes such as Ers, Ars, Vtgs, cyp19a, star, hsd3b, hsd17b3 and shh indicated the possible abnormal steroidogenesis, estrogenic or antiandrogen effects of PrP. Overall, the present results provided evidences for the toxigenicity and endocrine disruptive effects on the male mosquitofish of chronic PrP exposure, which highlights the need for more investigations of its potential health risks.

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Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels

Cited by 16 publications

References 43 publications

Activation of D1/D5 receptors ameliorates decreased intrinsic excitability of hippocampal neurons induced by neonatal blockade of N‐methyl‐d‐aspartate receptors

Activation of D1/D5 receptors ameliorates decreased intrinsic excitability of hippocampal neurons induced by neonatal blockade of N‐methyl‐d‐aspartate receptors

Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1

Endocrine Disruption of Propylparaben in the Male Mosquitofish (Gambusia affinis): Tissue Injuries and Abnormal Gene Expressions of Hypothalamic-Pituitary-Gonadal-Liver Axis

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