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Neurotoxicology and Teratology

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https://www.readbyqxmd.com/read/27888055/dietary-choline-levels-modify-the-effects-of-prenatal-alcohol-exposure-in-rats
#1
Nirelia M Idrus, Kristen R Breit, Jennifer D Thomas
Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor...
November 23, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27876652/isoflurane-exposure-leads-to-apoptosis-of-neurons-and-oligodendrocytes-in-20-and-40-day-old-rhesus-macaques
#2
Katie J Schenning, Kevin K Noguchi, Lauren Drew Martin, Francesca M Manzella, Omar H Cabrera, Gregory A Dissen, Ansgar M Brambrink
Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt to further describe the window of vulnerability to anesthetic neurotoxicity, we exposed P20 and P40 rhesus macaques to 5h of isoflurane anesthesia or no exposure (control animals). Brains were collected 3h later and examined immunohistochemically to analyze neuronal and glial apoptosis. Brains exposed to isoflurane displayed neuron and oligodendrocyte apoptosis distributed throughout cortex and white matter, respectively...
November 19, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27871903/review-of-preclinical-studies-on-pediatric-general-anesthesia-induced-developmental-neurotoxicity
#3
Jennifer L Walters, Merle G Paule
Thousands of infants and children undergo complicated surgical procedures that require prolonged periods of anesthesia and/or sedation each year. A growing body of preclinical research suggests pediatric anesthetics are harmful to the developing brain; yet, the extent to which these effects generalize to the clinical setting remains unclear. As there will be a continuing need for surgical and other interventions requiring sedation and/or anesthesia during the neonatal period, it seems clear that research efforts should focus on determining the extent to which general anesthetics can affect the developing brain as well as determining strategies for preventing or ameliorating the adverse effects associated with exposure to such agents...
November 18, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27856361/reprint-of-adolescent-cortical-thickness-pre-and-post-marijuana-and-alcohol-initiation
#4
REVIEW
Joanna Jacobus, Norma Castro, Lindsay M Squeglia, M J Meloy, Ty Brumback, Marilyn A Huestis, Susan F Tapert
Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, <3 alcohol use episodes, no marijuana use episodes)...
November 14, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27856360/sensitivity-to-isoflurane-anesthesia-increases-in-autism-spectrum-disorder-shank3-%C3%A2-c-mutant-mouse-model
#5
Changsheng Li, Michele Schaefer, Christy Gray, Ya Yang, Orion Furmanski, Sufang Liu, Paul Worley, C David Mintz, Feng Tao, Roger A Johns
Autism is a heterogeneous developmental disorder characterized by impaired social interaction, impaired communication skills, and restricted and repetitive behavior. The abnormal behaviors of these patients can make their anesthetic and perioperative management difficult. Evidence in the literature suggests that some patients with autism or specific autism spectrum disorders (ASD) exhibit altered responses to pain and to anesthesia or sedation. A genetic mouse model of one particular ASD, Phelan McDermid Syndrome, has been developed that has a Shank3 haplotype truncation (Shank3(+/Δc))...
November 14, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27856359/anesthetic-neurotoxicity-apoptosis-and-autophagic-cell-death-mediated-by-calcium-dysregulation
#6
Meirong Yang, Huafeng Wei
A number of findings suggested that general anesthetics induced neural cell death by apoptosis in various animal models. Although clinical evidence regarding the correlation between anesthetic exposures at young age and subsequent cognitive impairments remains unclear, repeated or consistent exposures to general anesthetics may be a potential harmful risk in developing human brains. The mechanisms underlying the anesthetic neurotoxicity have received extensive attention recently. We will attempt a brief review to summarize current understanding on the role of both apoptosis and autophagic cell death mediated by calcium dysregulation in anesthetic neurotoxicity...
November 14, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27826117/neonatal-inhibition-of-na-k-2cl-cotransporter-prevents-ketamine-induced-spatial-learning-and-memory-impairments
#7
Ryan A Stevens, Brandon D Butler, Saurabh S Kokane, Andrew W Womack, Qing Lin
Prolonged ketamine exposure in neonates at anesthetic doses is known to cause long-term impairments of learning and memory. A current theoretical mechanism explains this phenomenon as being neuro-excitotoxicity mediated by compensatory upregulation of N-methyl-d-aspartate receptors (NMDARs), which then initiates widespread neuroapoptosis. Additionally, the excitatory behavior of GABAergic synaptic transmission mediated by GABAA receptors (GABAARs), occurring during the early neuronal development period, is proposed as contributing to the susceptibility of neonatal neurons to ketamine-induced injury...
November 5, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27793659/do-anesthetics-harm-the-developing-human-brain-an-integrative-analysis-of-animal-and-human-studies
#8
Erica P Lin, Jeong-Rim Lee, Christopher S Lee, Meng Deng, Andreas W Loepke
Anesthetics permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects...
October 26, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27793660/reduced-expression-of-%C3%AE-5gabaa-receptors-elicits-autism-like-alterations-in-eeg-patterns-and-sleep-wake-behavior
#9
Lia Mesbah-Oskui, Antonello Penna, Beverley A Orser, Richard L Horner
A reduction in the activity of GABAA receptors, particularly α5 subunit-containing GABAA receptors (α5GABAARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABAARs (Gabra5(-/-)) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5(-/-) mice and wild-type mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed...
October 25, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27784630/minimally-invasive-biomarkers-of-general-anesthetic-induced-developmental-neurotoxicity
#10
X Zhang, F Liu, W Slikker, C Wang, M G Paule
The association of general anesthesia with developmental neurotoxicity, while nearly impossible to study in pediatric populations, is clearly demonstrable in a variety of animal models from rodents to nonhuman primates. Nearly all general anesthetics tested have been shown to cause abnormal brain cell death in animals when administered during periods of rapid brain growth. The ability to repeatedly assess in the same subjects adverse effects induced by general anesthetics provides significant power to address the time course of important events associated with exposures...
October 23, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27756629/developmental-manganese-neurotoxicity-in-rats-cognitive-deficits-in-allocentric-and-egocentric-learning-and-memory
#11
Robyn M Amos-Kroohs, Laurie L Davenport, Nina Atanasova, Zuhair I Abdulla, Matthew R Skelton, Charles V Vorhees, Michael T Williams
Manganese (Mn) is an essential element but neurotoxic at higher exposure levels. The effects of Mn overexposure (MnOE) on hippocampal and striatal-dependent learning and memory in rats were tested in combination with iron deficiency (FeD) and developmental stress that often co-occur with MnOE. Moderate FeD affects up to 15% of U.S. children and developmental stress is common in lower socio-economic areas where MnOE occurs. Pregnant Sprague-Dawley rats and their litters were housed in cages with or without (barren cage (BAR)) standard bedding from embryonic day (E)7 to postnatal day (P)28...
October 15, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27751818/neurogenesis-and-developmental-anesthetic-neurotoxicity
#12
Eunchai Kang, Daniel A Berg, Orion Furmanski, William M Jackson, Yun Kyoung Ryu, Christy D Gray, C David Mintz
The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure...
October 14, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27751817/prenatal-arsenic-exposure-alters-rest-nrsf-and-microrna-regulators-of-embryonic-neural-stem-cell-fate-in-a-sex-dependent-manner
#13
Christina R Tyler, Matthew T Labrecque, Elizabeth R Solomon, Xun Guo, Andrea M Allan
Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs)...
October 14, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27746264/repeated-measure-analyses-which-one-a-survey-of-statistical-models-and-recommendations-for-reporting
#14
Jacques P Maurissen, Thomas J Vidmar
Repeated-measure analysis of variance is a general term that can imply a number of different statistical models used to analyze data from studies in which measurements are taken from each subject on more than one occasion. Repeated-measure analyses encompass univariate models (with or without sphericity adjustment), multivariate models, mixed models, analysis of covariance, multilevel models, latent growth models, and hybrids of these models. These models are based on different assumptions, especially regarding correlations (sphericity) between within-subject factors, which comprise the variance-covariance matrix...
October 13, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27737797/toxicogenomic-profile-of-apoptotic-and-necrotic-sn56-basal-forebrain-cholinergic-neuronal-loss-after-acute-and-long-term-chlorpyrifos-exposure
#15
Paula Moyano, Javier Del Pino, María José Anadon, María Jesús Díaz, Gloria Gómez, María Teresa Frejo
Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce, both after acute and repeated exposure, learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. This effect was reported to be induced through apoptotic process, partially mediated by AChE overexpression, although neuronal necrosis was also described after CPF exposure...
October 10, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27634313/sexually-dimorphic-alterations-in-cannabinoid-receptor-density-depend-upon-prenatal-early-postnatal-history
#16
Diana Dow-Edwards, Ashley Frank, Wade, Jeremy Weedon, Sari Izenwasser
Recent research has demonstrated that the endogenous cannabinoid system is central to the brain's response to stress. As part of an ongoing collaboration, we sought to examine the effects of prenatal and early postnatal rearing and housing conditions on developing endocannabinoid systems. We compare brain cannabinoid receptors (CBR) in offspring of either prenatal vehicle intubated or non-treated dams (Experiment 1) or in rats derived from a vendor and shipped at weaning to a collaborating lab (Experiment 2)...
September 12, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27622724/long-lasting-behavioral-effects-in-neonatal-mice-with-multiple-exposures-to-ketamine-xylazine-anesthesia
#17
Lianyan Huang, Scott Hayes, Guang Yang
Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear...
September 10, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27616667/carbon-monoxide-and-anesthesia-induced-neurotoxicity
#18
Richard J Levy
The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria...
September 9, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27687470/adolescent-cortical-thickness-pre-and-post-marijuana-and-alcohol-initiation
#19
REVIEW
Joanna Jacobus, Norma Castro, Lindsay M Squeglia, M J Meloy, Ty Brumback, Marilyn A Huestis, Susan F Tapert
Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, <3 alcohol use episodes, no marijuana use episodes)...
September 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27616668/pituitary-lacks-sexual-dimorphism-and-displays-reduced-signal-intensity-on-t1-weighted-mri-in-adolescents-with-histories-of-heavy-prenatal-alcohol-exposure
#20
Eileen M Moore, M Alejandra Infante, Robyn Migliorini, Sarah N Mattson, Edward P Riley
Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure...
September 2016: Neurotoxicology and Teratology
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