Measuring infant memory: Utility of the visual paired-comparison test paradigm for studies in developmental neurotoxicology

Burbacher, Thomas M.; Grant, Kimberly S.

doi:10.1016/j.ntt.2012.06.003

Cited by 27 publications

(24 citation statements)

References 89 publications

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“…Novelty preference, an early indicator of recognition memory in human and nonhuman primate studies (Burbacher and Grant, 2012), was greater in alcohol-exposed than in control infants in the current study. This test was also used in the NHP binge-drinking model of Clarren (Clarren et al, 1992).…”

Section: Discussionsupporting

confidence: 45%

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Binge Drinking Prior to Pregnancy Detection in a Nonhuman Primate: Behavioral Evaluation of Offspring

Golub

Hogrefe

VandeVoort

2013

Alcohol Clin Exp Res

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Background Minimal scientific information is available to inform public health policy on binge drinking prior to pregnancy detection. The nonhuman primate provides a valuable animal model for examining consequences to reproduction and offspring function that may result from this common pattern of alcohol abuse. Methods Adult female rhesus monkeys were dosed with 1.5 g/kg-d ethanol by gavage two days/week beginning seven months prior to mating and continuing to pregnancy detection at 19–20 days gestation. Postnatal evaluation of control (n=6) and ethanol treated (n=4) infants included a neonatal neurobehavioral assessment, a visual paired comparison (cognitive) test at 35 days of age and mother-infant interaction at 100–112 days of age. Results Alcohol-exposed neonates did not differ from controls in posture and reflex measures. Longer durations of visual fixation, suggesting slower visual processing, and greater novelty preference were seen in the alcohol group. At early weaning age, as infants spent more time away from their dams, more of the reunions between mother and infant were initiated by the mothers in the alcohol-exposed group, suggesting a more immature mother-infant interaction. Conclusion Intermittent high dose alcohol exposure (binge drinking) discontinued at early pregnancy detection in rhesus monkey can result in altered behavioral function in the infant. Mediating effects on ovum, reproductive tract and early embryo can be explored in this model. Studies of longer-term consequences in human populations and animal models are needed.

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Section: Discussionsupporting

confidence: 45%

“…VPC is a test of higher cognitive function used in both human and nonhuman primate infants (Burbacher and Grant, 2012). For VPC, the infant was swaddled in a towel and hand-held with its head free in front of the testing apparatus in a darkened room.…”

Section: Methodsmentioning

confidence: 99%

Binge Drinking Prior to Pregnancy Detection in a Nonhuman Primate: Behavioral Evaluation of Offspring

Golub

Hogrefe

VandeVoort

2013

Alcohol Clin Exp Res

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“…30 On problems using simple geometric forms, UCO saline infants performed poorly, while infants receiving HT+Epo provided significant evidence of recognition memory (p<0.05). This finding suggests a disruption in the early memory processing of UCO infants but also, a sparing of some adverse memory effects in animals receiving treatment.…”

Section: Resultsmentioning

confidence: 96%

Concurrent Erythropoietin and Hypothermia Treatment Improve Outcomes in a Term Nonhuman Primate Model of Perinatal Asphyxia

et al. 2013

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Background: Up to 65% of untreated infants suffering from moderate to severe hypoxic-ischemic encephalopathy (HIE) are at risk of death or major disability. Therapeutic hypothermia (HT) reduces this risk to approximately 50% (number needed to treat: 7-9). Erythropoietin (Epo) is a neuroprotective treatment that is promising as an adjunctive therapy to decrease HIE-induced injury because Epo decreases apoptosis, inflammation, and oxidative injury and promotes glial cell survival and angiogenesis. We hypothesized that HT and concurrent Epo will be safe and effective, improve survival, and reduce moderate-severe cerebral palsy (CP) in a term nonhuman primate model of perinatal asphyxia. Methodology: Thirty-five Macacanemestrina were delivered after 15-18 min of umbilical cord occlusion (UCO) and randomized to saline (n = 14), HT only (n = 9), or HT+Epo (n = 12). There were 12 unasphyxiated controls. Epo (3,500 U/kg × 1 dose followed by 3 doses of 2,500 U/kg, or Epo 1,000 U/kg/day × 4 doses) was given on days 1, 2, 3, and 7. Timed blood samples were collected to measure plasma Epo concentrations. Animals underwent MRI/MRS and diffusion tensor imaging (DTI) at <72 h of age and again at 9 months. A battery of weekly developmental assessments was performed. Results: UCO resulted in death or moderate-severe CP in 43% of saline-, 44% of HT-, and 0% of HT+Epo-treated animals. Compared to non-UCO control animals, UCO animals exhibit poor weight gain, behavioral impairment, poor cerebellar growth, and abnormal brain DTI. Compared to UCO saline, UCO HT+Epo improved motor and cognitive responses, cerebellar growth, and DTI measures and produced a death/disability relative risk reduction of 0.911 (95% CI -0.429 to 0.994), an absolute risk reduction of 0.395 (95% CI 0.072-0.635), and a number needed to treat of 2 (95% CI 2-14). The effects of HT+Epo on DTI included an improved mode of anisotropy, fractional anisotropy, relative anisotropy, and volume ratio as compared to UCO saline-treated infants. No adverse drug reactions were noted in animals receiving Epo, and there were no hematology, liver, or kidney laboratory effects. Conclusions/Significance: HT+Epo treatment improved outcomes in nonhuman primates exposed to UCO. Adjunctive use of Epo combined with HT may improve the outcomes of term human infants with HIE, and clinical trials are warranted.

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“…Likewise, in the present study, we did not find neuropathological or behavioral abnormalities in animals receiving TCVs. Neurobehavioral assessments followed very detailed protocols that have been used at the primate facility for more than three decades (35,36). There were three testers involved in the scoring of social behavior data and each passed periodic reliability training to high standards.…”

Section: Discussionmentioning

confidence: 99%

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

Gadad

Yazdani

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosalcontaining vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.pediatric vaccines | autism | rhesus macaque | thimerosal | neuropathology

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Measuring infant memory: Utility of the visual paired-comparison test paradigm for studies in developmental neurotoxicology

Cited by 27 publications

References 89 publications

Binge Drinking Prior to Pregnancy Detection in a Nonhuman Primate: Behavioral Evaluation of Offspring

Binge Drinking Prior to Pregnancy Detection in a Nonhuman Primate: Behavioral Evaluation of Offspring

Concurrent Erythropoietin and Hypothermia Treatment Improve Outcomes in a Term Nonhuman Primate Model of Perinatal Asphyxia

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

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