scholarly journals Prenatal alcohol exposure affects developmental differentiation of interictal discharges in septal and temporal hippocampus

2021 ◽  
Author(s):  
Maria-Eleni Evangelaki ◽  
Caterina Psarropoulou
Keyword(s):  
Prenatal Alcohol Exposure ◽  
Hippocampal Slices ◽  
Alcohol Exposure ◽  
Receptor Activation ◽  
Network Function ◽  
Epileptiform Discharges ◽  
Discharge Duration ◽  
Prenatal Alcohol ◽  
Interictal Discharges

Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in vitro in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a Young (Y, 21-30 Postnatal Days, PND) or Adult (A, 60 PND) age, with controls from same age Normal rats (N). Synchronous spontaneous interictal-type epileptiform discharges (IEDs) were induced by bathing the slices in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50µM) and were recorded from CA1 pyramidal layer of Temporal (T) and Septal slices (S). Hippocampal slices readily generated IEDs following NMDA receptor activation or K+ conductance block, with frequency and duration depending on location (septal or temporal), age, the activating mechanism, and prior conditioning (N or PAE). From the two media, 4-AP induced higher frequency (always), shorter duration (mostly) IEDs compared to Mg 2+-free ACSF. Temporal IED frequency increased with age, whereas Septal was stable, indicating an earlier maturation of the latter part. The hippocampal "T to S" (high to low) excitability gradient appeared at/later than the end of the first postnatal month and concerned mostly discharge frequency. Discharge duration generally decreased with maturation but appeared to depend on many factors including conditioning. Prenatal alcohol exposure differentiated the control of synchronous discharges by NMDA receptors and K+ conductances, and their developmental evolution, thus suggesting potential mechanisms for aberrant hippocampal neuronal network function.

scholarly journals Prenatal alcohol exposure is a leading cause of interneuronopathy in humans

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Florent Marguet ◽  
Gaëlle Friocourt ◽  
Mélanie Brosolo ◽  
Fanny Sauvestre ◽  
Pascale Marcorelles ◽  
...  
Keyword(s):  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
In Vitro Models ◽  
Cortical Plate ◽  
Gabaergic Interneurons ◽  
Cortical Density ◽  
Deep Layers ◽  
Prenatal Alcohol ◽  
Ganglionic Eminences

AbstractAlcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks’ gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.e., 34 weeks’ gestation. Results were compared with those obtained in 17 control brains aged 14 weeks of gestation to 35 postnatal months. We also focused on interneuron vascular migration along the cortical microvessels by confocal microscopy with double immunolabellings using Glut1, GABA and calretinin. Semi-quantitative and quantitative analyses of GABAergic and calretininergic interneuron density allowed us to identify an insufficient and delayed production of GABAergic interneurons in the ganglionic eminences during the two first trimesters of the pregnancy and a delayed incorporation into the laminar structures of the frontal cortex. Moreover, a mispositioning of GABAergic and calretininergic interneurons persisted throughout the foetal life, these cells being located in the deep layers instead of the superficial layers II and III. Moreover, vascular migration of calretininergic interneurons within the cortical plate was impaired, as reflected by low numbers of interneurons observed close to the cortical perforating vessel walls that may in part explain their abnormal intracortical distribution. Our results are globally concordant with those previously obtained in mouse models, in which alcohol has been shown to induce an interneuronopathy by affecting interneuron density and positioning within the cortical plate, and which could account for the neurological disabilities observed in children with foetal alcohol disorder spectrum.

Ictal Epileptiform Activity in the CA3 Region of Hippocampal Slices Produced by Pilocarpine

1998 ◽  
Vol 79 (6) ◽  
pp. 3019-3029 ◽  
Author(s):  
Paul A. Rutecki ◽  
Yili Yang
Keyword(s):  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Extracellular Potassium ◽  
Muscarinic Agonist ◽  
Epileptiform Discharges ◽  
Artificial Cerebrospinal Fluid ◽  
Discharge Duration ◽  
Interictal Discharges ◽  
Ca3 Region

Rutecki, Paul A. and Yili Yang. Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine. J. Neurophysiol. 79: 3019–3029, 1998. Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated with the later development of chronic recurrent seizures. When applied to rat hippocampal slices, pilocarpine (10 μM) produced brief (<200 ms) epileptiform discharges that resembled interictal activity that occurs between seizures, as well as more prolonged synchronous neuronal activation that lasted seconds (3–20 s), and was comparable to ictal or seizures-like discharges. We assessed the factors that favored ictal patterns of activity and determined the biophysical properties of the ictal discharge. The probability of observing ictal discharges was increased when extracellular potassium ([K+]o) was increased from 5 to 7.5 mM. Raising [K+]o to 10 mM resulted in loss of ictal patterns and, in 20 of 34 slices, desynchronization of epileptiform activity. Making the artificial cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+]o, but shifted 7.5 mM [K+]o ACSF patterns to interictal discharges or desynchronized activity. Conversely, increasing osmolality suppressed ictal patterns. The pilocarpine-induced ictal discharges were blocked by atropine (1 μM, n = 5), a muscarinic antagonist, and pirenzepine (1 μM, n = 6), a selective M1 receptor antagonist. Kainate/α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor blockade stopped all epileptiform activity ( n = 8). The N-methyl-d-aspartate antagonist d,l-2-amino-5-phosphonovaleric acid (100 μM, n = 34) did not change the pattern of epileptiform activity but significantly increased the rate of interictal discharges and prolonged the duration of ictal discharges. The ictal discharge was characterized intracellularly by a depolarization that was associated with action potential generation and persisted as a membrane oscillation of 4–10 Hz. The ictal oscillations reversed in polarity at −22.7 ± 2.2 mV ( n = 11) with current-clamp recordings and −20.9 ± 3.1 mV ( n = 7) with voltage-clamp recordings. The reversal potential of the ictal discharge in the presence of the γ-aminobutyric acid-A blocker bicuculline (10 μM, n = 6) was −2.2 ± 2.6 mV and was significantly different from that measured without bicuculline. Bicuculline added to 7.5 mM [K+]o and 10 μM pilocarpine did not cause epileptiform activity to change pattern but significantly increased the rate of interictal discharges and prolonged the ictal discharge duration. Both synaptic and nonsynaptic mechanisms are important for the generation of ictal patterns of epileptiform activity. Although the synchronous epileptiform activity produced by pilocarpine required fast glutamate-mediated synaptic transmission, the transition from an interictal to ictal pattern of activity depended on [K+]o and could be influenced by extracellular space.

Pattern-and age-dependency of the antiepileptic effects induced by valproic acid in the rat hippocampus

1991 ◽  
Vol 69 (9) ◽  
pp. 1301-1304 ◽  
Author(s):  
Yukiko Fueta ◽  
Massimo Avoli
Keyword(s):  
Valproic Acid ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Adult Rats ◽  
Adult Rat ◽  
Young Rats ◽  
Epileptiform Discharges ◽  
Interictal Epileptiform Discharges ◽  
Interictal Discharges

The effects induced by the antiepileptic drug valproic acid were studied in the CA3 subfield of in vitro hippocampal slices obtained from young (16- to 27-day-old) and adult (over 60-day-old) rats. Spontaneous epileptiform discharges were induced by the addition of the convulsant 4-aminopyridine to the medium. Valproic acid (0.5 mM) selectively blocked the ictal epileptiform discharges in slices obtained from young rats. Interictal epileptiform discharges disappeared during perfusion with higher doses of valproic acid (2 mM). This blockade of interictal epileptiform activity was not observed when valproic acid (0.5–5 mM) was tested in hippocampal slices from adult rats. Thus, in the hippocampus of young rats, 4-aminopyridine-induced ictal activity is more sensitive to valproic acid than are interictal discharges. Moreover, valproic acid is effective in controlling interictal discharges in the young, but not in the adult rat hippocampus.Key words: valproic acid, epilepsy, 4-aminopyridine, hippocampus, rat.

scholarly journals The Effects of Early Prenatal Alcohol Exposure on Epigenome and Embryonic Development

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1095
Author(s):  
Essi Wallén ◽  
Pauliina Auvinen ◽  
Nina Kaminen-Ahola
Keyword(s):  
Developmental Disorders ◽  
Current Knowledge ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Neurological Deficits ◽  
Sensitive Period ◽  
Western World ◽  
Increased Risk ◽  
Prenatal Alcohol

Prenatal alcohol exposure is one of the most significant causes of developmental disability in the Western world. Maternal alcohol consumption during pregnancy leads to an increased risk of neurological deficits and developmental abnormalities in the fetus. Over the past decade, several human and animal studies have demonstrated that alcohol causes alterations in epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs. There is an increasing amount of evidence that early pregnancy is a sensitive period for environmental-induced epigenetic changes. It is a dynamic period of epigenetic reprogramming, cell divisions, and DNA replication and, therefore, a particularly interesting period to study the molecular changes caused by alcohol exposure as well as the etiology of alcohol-induced developmental disorders. This article will review the current knowledge about the in vivo and in vitro effects of alcohol exposure on the epigenome, gene regulation, and the phenotype during the first weeks of pregnancy.

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

Prenatal alcohol exposure and signs of minor neurological dysfunction at preschool age

2000 ◽  
Vol 42 (8) ◽  
pp. 508-514 ◽  
Author(s):  
Béatrice Larroque ◽  
Monique Kaminski ◽  
Phillipe Dehaene ◽  
Damien Subtil ◽  
Denis Querleu
Keyword(s):  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Preschool Age ◽  
Neurological Dysfunction ◽  
Minor Neurological Dysfunction ◽  
Prenatal Alcohol

Impact of Moderate Prenatal Alcohol Exposure on Problem Behaviors in Preschool and School Children

2014 ◽  
Vol 46 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Manuela Pfinder ◽  
Stefan Liebig ◽  
Reinhold Feldmann
Keyword(s):  
Problem Behaviors ◽  
Tobacco Smoke ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Smoke Exposure ◽  
Low Ses ◽  
German Health ◽  
Kiggs Study ◽  
Strengths And Difficulties ◽  
Prenatal Alcohol

Data on the relation between moderate prenatal alcohol exposure (PAE) and behavioral disorders are inconsistent, and this raises new questions. We examined (1) the association between moderate PAE and problem behaviors and (2) whether these associations differed by levels of socioeconomic status (SES), fetal smoke exposure, or exposure to environmental tobacco smoke (ETS). Data were taken from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study. Parents evaluated children’s behaviors using the Strengths and Difficulties Questionnaire (SDQ). Results showed a slight, but insignificant, increase of problem behaviors in children with moderate PAE. In 3- to 6-year-olds, PAE had a stronger effect on hyperactivity/inattention in combination with fetal smoke exposure (odds ratio = 2.82), than did PAE alone. Effects were not stronger in low-SES children, but they were stronger in children with ETS. We conclude that moderate PAE might have adverse effects on neurodevelopment, with stronger effects in disadvantaged populations. To confirm our preliminary findings, further research should be conducted.

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