Melatonin prevents learning disorders in brain-lesioned newborn mice

Bouslama, Mohamed; Renaud, Jean‐François; Olivier, Paul; Fontaine, R; Matrot, Boris; Gressèns, Pierre; Gallego, Jorge

doi:10.1016/j.neuroscience.2007.09.030

Cited by 51 publications

(30 citation statements)

References 36 publications

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“…Other proposed methods of classical conditioning in rodent pups require important experimenter manipulation, for example stroking [6][7][8] or oral milk infusion in nutritive conditioning experiments in rat [22]. These methods are therefore poorly suited for high-throughput behavioral screening.…”

Section: Discussionmentioning

confidence: 99%

“…The test apparatus was a place preference system previously described [6][7][8]13]. Briefly, this apparatus (Fig.…”

Section: Test Setupmentioning

confidence: 99%

“…Previous studies showed that pairing artificial odors (conditioned stimuli, (CS)) and stroking with a brush (unconditioned stimulus, as a surrogate of maternal licking and grooming) induced an effective conditioned odor preference in newborn mice [6]. This conditioning method proved efficient to show learning deficits in newborn mice with brain lesions similar to that of preterm infants, and to assess functional efficacy of experimental neuroprotective treatments [7,8]. However, odor-stroke conditioning is difficult to standardize, due to strong experimenter effects on stroking, which prompted us to broaden the range of available conditioning methods in newborn mice.…”

Section: Introductionmentioning

confidence: 99%

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Olfactory classical conditioning in neonatal mouse pups using thermal stimuli

Bollen¹,

Matrot²,

Ramanantsoa³

et al. 2012

Behavioural Brain Research

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a b s t r a c tMouse models are increasingly used to investigate genetic contributions to developmental disorders in children, especially newborns. In particular, early cognitive assessment in newborn mice is critical to evaluate pediatric drug efficacy and toxicity. Unfortunately, methods for behavioral tests in newborn mice are scarce. Therefore, developing such tests for newborn mice is a priority challenge for neurogenetics and pharmacological research. The aim of the present study was to develop a conditioning method well suited to high-throughput cognitive screening in newborn mice. To this end, we developed an odorpreference conditioning test using ambient temperature as an unconditioned stimulus (US) and artificial odors as conditioned stimuli (CS). First, we showed that mouse pups move toward the thermoneutral temperature when offered a choice between a thermoneutral and cold environment, thus showing thermotaxis. Second, we conducted a classical conditioning paradigm in pups aged six to ten days. In terms of central nervous system development, this period corresponds to extreme prematurity to early postterm period in humans. During acquisition, the pups were alternatively exposed to odor CS paired with either cold or warm temperatures. Immediately after acquisition, the pups underwent a two-odor choice test, which showed preference for the odor previously paired with the warm temperature, thus showing conditioning. The proposed paradigm is easy to conduct, and requires modest experimenter interference. The method is well suited for high-throughput screening of early associative disorders in newborn mice.

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Section: Discussionmentioning

confidence: 99%

“…The test apparatus was a place preference system previously described [6][7][8]13]. Briefly, this apparatus (Fig.…”

Section: Test Setupmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Olfactory classical conditioning in neonatal mouse pups using thermal stimuli

Bollen¹,

Matrot²,

Ramanantsoa³

et al. 2012

Behavioural Brain Research

View full text Add to dashboard Cite

show abstract

“…Specifically, the area of the excitotoxic lesion was dissected by excising an area 2 × 2 mm of the whole depth of the cortex and underlying subcortical white matter from the injection site at each age. Although the necessity to take the entire lesion area for analysis precluded analysis of lesion size, animals performed in parallel for a separate study had the expected lesion size for this highly reproducible model [28,[33][34][35] . Each treatment group comprised 7-10 animals.…”

Section: Neonatal Excitotoxic Brain Lesions and Sample Collectionmentioning

confidence: 99%

Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

Blaise

Schwendimann

Chhor³

et al. 2017

Dev Neurosci

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Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy.

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“…69 Melatonin has also been shown to protect against learning disorders in hypoxic-ischemic injured neonatal rats 70 and excitotoxic brain-lesioned newborn mice. 71 Augmentation of another endogenously generated substance with neuroprotective potential, erythropoietin (EPO), 72,73 has shown promise against NMDAR-antagonist neurotoxicity in rat 74 and mouse 75 neonates, in human newborns with hypoxicischemic encephalopathy, 76 and in extremely preterm human infants. 77 What about hypothermia and neonatal brain damage?…”

Section: What Might Be Done?mentioning

confidence: 99%

Developmental Disability in the Young and Postoperative Cognitive Dysfunction in the Elderly After Anesthesia and Surgery: Do Data Justify Changing Clinical Practice?

Cottrell

Hartung

2012

Mount Sinai J Medicine

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The assumption that anesthesia has no serious, long‐term, adverse central nervous system consequences may be true for most patients between 6 months and 60 years of age. However, for patients younger than 6 months or older than 60 years, that status quo assumption is under challenge from a growing body of evidence. Fetuses and newborns appear to be at risk because systems that would enable them to fully recover from the effects of more than 2 hours of anesthesia are still in development. In distinction, the elderly appear to be at risk because systems that once enabled them to fully recover have ever‐diminishing capacity. Even for those between the age of 6 months and 60 years, full recovery may require replacing apoptosed neurons and pruning overabundant dendritic spines … perhaps leaving patients not quite the same person that they were before they were anesthetized. Mt Sinai J Med 79:75–94, 2012. © 2012 Mount Sinai School of Medicine

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Melatonin prevents learning disorders in brain-lesioned newborn mice

Cited by 51 publications

References 36 publications

Olfactory classical conditioning in neonatal mouse pups using thermal stimuli

Olfactory classical conditioning in neonatal mouse pups using thermal stimuli

Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

Developmental Disability in the Young and Postoperative Cognitive Dysfunction in the Elderly After Anesthesia and Surgery: Do Data Justify Changing Clinical Practice?

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