scholarly journals Acute Ethanol Exposure during Synaptogenesis Rapidly Alters Medium Spiny Neuron Morphology and Synaptic Protein Expression in the Dorsal Striatum

2021 ◽  
Vol 23 (1) ◽  
pp. 290
Author(s):  
Erin Clabough ◽  
James Ingersoll ◽  
Tyler Reekes ◽  
Alyssa Gleichsner ◽  
Amy Ryan
Keyword(s):  
Fetal Alcohol Spectrum Disorders ◽  
Neuronal Response ◽  
Ethanol Exposure ◽  
Neuronal Morphology ◽  
Medium Spiny Neuron ◽  
Ethanol Administration ◽  
High Dose ◽  
Normal Brain ◽  
Synaptic Protein ◽  
Spine Density

Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.

scholarly journals Effects of Ethanol Exposure and Withdrawal on Neuronal Morphology in the Agranular Insular and Prelimbic Cortices: Relationship with Withdrawal-Related Structural Plasticity in the Nucleus Accumbens

2019 ◽  
Vol 9 (8) ◽  
pp. 180 ◽  
Author(s):  
Madeline E. Frost ◽  
Veronica L. Peterson ◽  
Clark W. Bird ◽  
Brian McCool ◽  
Derek A. Hamilton
Keyword(s):  
Nucleus Accumbens ◽  
Insular Cortex ◽  
Ethanol Exposure ◽  
Dendritic Morphology ◽  
Neuronal Morphology ◽  
Prelimbic Cortex ◽  
Spine Density ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Dendritic Length

The present study investigated the effects of chronic intermittent ethanol exposure and withdrawal on dendritic morphology and spine density in the agranular insular and prelimbic cortices. Adult male Sprague–Dawley rats were passively exposed to vaporized ethanol (~37 mg/L; 12 h/day) or air (control) for ten consecutive days. Dendritic length, branching, and spine density were quantified in layer II/III pyramidal neurons 24 hours or seven days following the final ethanol exposure. Compared to unexposed control animals there were structural alterations on neurons in the prelimbic cortex, and to a lesser extent the agranular insular cortex. The most prominent ethanol-related differences were the transient increases in dendritic length and branching in prelimbic neurons at 24 h post-cessation, and increased mushroom-shaped spines at seven days post-cessation. The results obtained in the prelimbic cortex are the opposite of those previously reported in the nucleus accumbens core (Peterson, et al. 2015), suggesting that these regions undergo distinct functional adaptations following ethanol exposure and withdrawal.

scholarly journals Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated β-Catenin Degradation in Neonatal Mice

2020 ◽  
Vol 10 (5) ◽  
pp. 271
Author(s):  
Shivakumar Subbanna ◽  
Balapal S. Basavarajappa
Keyword(s):  
Fetal Alcohol Spectrum Disorders ◽  
Cannabinoid Receptor ◽  
Ethanol Exposure ◽  
High Dose ◽  
Fetal Alcohol ◽  
Signaling Mechanism ◽  
Protein Levels ◽  
Abc Protein ◽  
Fetal Alcohol Spectrum

Alcohol consumption by pregnant women may produce neurological abnormalities that affect cognitive processes in children and are together defined as fetal alcohol spectrum disorders (FASDs). However, the molecular underpinnings are still poorly defined. In our earlier studies, we found that ethanol exposure of postnatal day 7 (P7) mice significantly induced widespread neurodegeneration mediated via endocannabinoids (eCBs)/cannabinoid receptor type 1 (CB1R). In the current study, we examined changes in the β-catenin protein levels that are involved in the regulation of neuronal function including neuronal death and survival. We found that moderate- and high-dose postnatal ethanol exposure (PEE) significantly reduced active-β-catenin (ABC) (non-phosphorylated form) protein levels in the hippocampus (HP) and neocortex (NC). In addition, we found that moderate- and high-dose PEE significantly increased the phosphorylated-β-catenin (p-β-catenin)/ABC ratios in the HP and NC. Antagonism/null mutation of CB1R before PEE to inhibit CC3 production mitigated the loss of ABC protein levels. Collectively, these findings demonstrated that the CB1R/β-catenin signaling mechanism causes neurodegeneration in neonatal mouse brains following PEE.

scholarly journals Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

2019 ◽  
Vol 116 (22) ◽  
pp. 10943-10951 ◽  
Author(s):  
Pierre Montay-Gruel ◽  
Munjal M. Acharya ◽  
Kristoffer Petersson ◽  
Leila Alikhani ◽  
Chakradhar Yakkala ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Neuronal Morphology ◽  
High Dose ◽  
Oxygen Species ◽  
Spine Density ◽  
Neuroprotective Effects ◽  
Tumor Bed ◽  
Conventional Dose ◽  
Stress Dependent

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s−1). Compared with conventional dose-rate (CONV; 0.07–0.1 Gy⋅s−1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.

scholarly journals Long-Term Ethanol Consumption Leadsto Lung Tissue Oxidative Stress and Injury

2010 ◽  
Vol 3 (6) ◽  
pp. 414-420 ◽  
Author(s):  
Subir Kumar Das ◽  
Sukhes Mukherjee
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Matrix Metalloproteinase ◽  
Lung Tissue ◽  
Ethanol Consumption ◽  
Ethanol Exposure ◽  
Lung Homogenate ◽  
Ethanol Administration ◽  
Metalloproteinase Activity

Background: Alcohol abuse is a systemic disorder. The deleterious health effects of alcohol consumption may result in irreversible organ damage. By contrast, there currently is little evidence for the toxicity of chronic alcohol use on lung tissue. Hence, in this study we investigated long-term effects of ethanol in the lung.Results: Though body weight of rats increased significantly with duration of exposure compared to its initial weight, there was no significant change in relative weight (g/100 g body weight) of lung due to ethanol exposure. The levels of thiobarbituric acid reactive substances (TBARS), nitrite, protein carbonyl, oxidized glutathione (GSS G), redox ratio (GSS G/ GSH ) and GST activity elevated; while reduced glutathione (GSH ) level and activities of glutathione reductase (GR), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and Na+K+ATPase reduced significantly with duration of ethanol exposure in the lung homogenate compared to the control group. Total matrix metalloproteinase activity elevated in the lung homogenate with time of ethanol consumption. Histopathologic examination also demonstrated that severity of lung injury enhanced with duration of ethanol exposure.Methods: 16–18 week-old male albino Wistar strain rats weighing 200–220 g were fed with ethanol (1.6 g/kg body weight/day) up to 36 weeks. At the end of the experimental period, blood samples were collected from reteroorbital plexus to determine blood alcohol concentration and the animals were sacrificed. Various oxidative stress-related biochemical parameters, total matrix metalloproteinase activity and histopathologic examinations of the lung tissues were performed.Conclusions: Results of this study indicate that long-term ethanol administration aggravates systemic and local oxidative stress, which may be associated with lung tissue injury.

scholarly journals Susac's Syndrome

2011 ◽  
Vol 38 (2) ◽  
pp. 335-337 ◽  
Author(s):  
Kevin Lian ◽  
Rekha Siripurapu ◽  
Robert Yeung ◽  
Julia Hopyan ◽  
Kenneth T. Eng ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
White Matter Hyperintensities ◽  
Brain Biopsy ◽  
High Dose ◽  
Normal Brain ◽  
Left Hand ◽  
Elevated Protein ◽  
Fluid Attenuated Inversion Recovery ◽  
History Of ◽  
Previous Medical History

A 40-year-old woman with no significant previous medical history presented with a three month history of ataxia, confusion, memory difficulties, and headaches. Physical examination revealed numbness in the left hand, but was otherwise unremarkable. Magnetic resonance imaging fluid-attenuated inversion recovery (MRI FLAIR) images demonstrated multiple small white matter hyperintensities, including lesions involving the corpus callosum. There were also deep gray nuclei lesions (Figure 1). The corpus callosum lesions involved the central fibers (Figure 2). Post gadolinium T1 images demonstrated enhancement of some of the lesions as well as extensive perivascular and leptomeningeal enhancement (Figure 3). Extensive infectious serology, autoimmune panel, and paraneoplastic antibodies were negative. Lumbar puncture revealed elevated protein (1116 mg/L), but was otherwise normal. Brain biopsy indicated no apparent pathology. The patient was tentatively diagnosed with acute encephalopathy and treated with high dose steroids seven days after presentation. She was subsequently discharged and was sent for rehabilitation.

scholarly journals A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

2011 ◽  
Vol 19 (2) ◽  
pp. 99 ◽  
Author(s):  
Takanori Miki ◽  
Simon J Harris ◽  
Peter Wilce ◽  
Yoshiki Takeuchi ◽  
Kuldip S Bedi
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Ethanol Exposure ◽  
Learning Ability ◽  
Ethanol Ingestion ◽  
High Dose ◽  
Postnatal Life ◽  
Numerical Density ◽  
Rat Pups ◽  
Early Postnatal Life

Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS) in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET), separation controls (SC) and mother reared controls (MRC) were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to the ethanol exposure.

scholarly journals The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander GJ Skorput ◽  
Stephanie M Lee ◽  
Pamela WL Yeh ◽  
Hermes H Yeh
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Fetal Alcohol Spectrum Disorders ◽  
Behavioral Flexibility ◽  
Ethanol Exposure ◽  
Embryonic Mouse ◽  
Form And Function ◽  
Tangential Migration ◽  
And Function

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.

Neurobiology of Fetal Alcohol Spectrum Disorders

2017 ◽  
Author(s):  
Carmen Lopez-Arvizu ◽  
Carmel Bogle ◽  
Harolyn M.E. Belcher
Keyword(s):  
Hormonal Regulation ◽  
Maternal Nutrition ◽  
Fetal Alcohol Spectrum Disorders ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Fetal Alcohol ◽  
Wide Range ◽  
Spectrum Disorders ◽  
The Impact ◽  
Fetal Alcohol Spectrum

Prenatal exposure to ethanol can result in a wide range of clinical presentations that are grouped under the term “Fetal Alcohol Spectrum Disorders” (FASD). The direct cellular teratogenic effects of ethanol on fetal neurodevelopment include damage to cell survival, proliferation, and migration mechanisms. Dysregulation of neurotransmission and alteration of genetic transcription have also been implicated in the neurotoxic effects of prenatal ethanol exposure. These deleterious events lead to brain volume reduction, corpus callosum dysgenesis, cerebellar, and other neuroanatomical anomalies that have been observed in individuals with FASD. Beyond direct ethanol-induced insults, the impact that ethanol has on maternal nutrition, metabolism, hormonal regulation, and placental physiology also adversely effects fetal development. The complex interactions between numerous neurobiological and psychosocial mechanisms that hinder optimal fetal neurodevelopment are reflected by the heterogeneous clinical presentation of FASD, including impaired growth, dysmorphic facial features, and cognitive and behavioral disorders.

scholarly journals Effects of prenatal ethanol exposure on the lungs of postnatal lambs

2011 ◽  
Vol 300 (1) ◽  
pp. L139-L147 ◽  
Author(s):  
Foula Sozo ◽  
Melissa Vela ◽  
Victoria Stokes ◽  
Kelly Kenna ◽  
Peter J. Meikle ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Phospholipid Composition ◽  
Lavage Fluid ◽  
Ethanol Exposure ◽  
Cytokine Gene Expression ◽  
Ethanol Administration ◽  
Mrna Levels ◽  
Prenatal Ethanol Exposure ◽  
Treatment Groups

Prenatal ethanol exposure increases collagen deposition and alters surfactant protein (SP) expression and immune status in lungs of near-term fetal sheep. Our objectives were to determine 1) whether these prenatal effects of repeated gestational ethanol exposure persist after birth and 2) whether surfactant phospholipid composition is altered following prenatal ethanol exposure. Pregnant ewes were chronically catheterized at 90 days of gestational age (DGA) and given a 1-h daily infusion of ethanol (0.75 g/kg, n = 9) or saline ( n = 7) from 95 to 135 DGA; ethanol administration ceased after 135 DGA. Lambs were born naturally at full term (146 ± 0.5 DGA). Lung tissue was examined at 9 wk postnatal age for alterations in structure, SP expression, and inflammation; bronchoalveolar lavage fluid was examined for alterations in surfactant phospholipid composition. At 134 DGA, surfactant phospholipid concentration in amniotic fluid was significantly reduced ( P < 0.05) by ethanol exposure, and the composition was altered. In postnatal lambs, there were no significant differences between treatment groups in birth weight, postnatal growth, blood gas parameters, and lung weight, volume, tissue fraction, mean linear intercept, collagen content, proinflammatory cytokine gene expression, and bronchoalveolar lavage fluid surfactant phospholipid composition. Although SP-A, SP-B, and SP-C mRNA levels were not significantly different between treatment groups, SP-D mRNA levels were significantly greater ( P < 0.05) in ethanol-treated animals; as SP-D has immunomodulatory roles, innate immunity may be altered. The adverse effects of daily ethanol exposure during late gestation on the fetal lung do not persist to 2 mo after birth, indicating that the developing lung is capable of repair.

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