Treatment-induced prevention of learning deficits in newborn mice with brain lesions.
Perinatal brain injuries often result in irreversible learning disabilities, which manifest in early childhood. The molecular and cellular mechanisms of these injuries and potential pharmacological treatments are emerging, chiefly from studies in newborn rodents. In newborn mice, experimentally induced lesions can be dramatically reduced by appropriate neuroprotective treatments. However, the early effectiveness of these treatments in preserving cognition remained unknown. Here, we addressed this issue by using intracerebral ibotenate to induce excitotoxic brain lesions in 5-day-old mice (postnatal day 5). On postnatal days 6-7, we tested spontaneous preference for maternal odors, as an index of odor memory, and conditioned preference for an artificial odor previously paired with stroking, as an index of associative learning. Brain-lesioned newborn mice showed normal general status and preference for maternal odors. In contrast, odor conditioning was severely impaired. A previous study showed that fructose 1,6-biphosphate acted as a neuroprotective agent which significantly reduced neocortical lesion size. In the present study, treating the newborn mice with fructose 1,6-biphosphate 15 min before the ibotenate injection reduced neocortical lesion size and restored conditioning. This demonstrates, for the first time, that neuroprotective treatment can protect some features of early cognition.
Bouslama
M
M
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France.
Chauvière
L
L
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France.
Fontaine
R H
RH
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France.
Matrot
B
B
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France.
Gressens
P
P
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France.
Gallego
J
J
INSERM U676, Robert Debré Hospital, 48 bvd Sérurier, 75019 Paris, France; University Paris 7, Denis Diderot Medical School, IFR02, 10 av de Verdun, 75010 Paris, France. Electronic address: gallego@rdebre.inserm.fr.
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005635:Fructosediphosphates / Q000627:therapeutic use*; D007051:Ibotenic Acid / Q000633:toxicity; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009812:Odorants; D011247:Pregnancy; D013997:Time Factors
D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D007051:Ibotenic Acid; C029063:fructose-1,6-diphosphate