Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats.
There is no established treatment for the long-term effects produced by perinatal asphyxia. Thus, we investigated the neuroprotection provided by nicotinamide against the effects elicited by perinatal asphyxia on hippocampus and behaviour observed at 30-90 days of age. Asphyxia was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver rats into a water bath at 37 degrees C for 20 min. Caesarean-delivered siblings were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. The animals were examined for morphological changes in hippocampus, focusing on delayed cell death and mossy fibre sprouting, and behaviour, focusing on cognitive behaviour and anxiety. At the age of 30-45 days, asphyxia-exposed rats displayed (1) increased apoptosis, assessed in whole hippocampus by nuclear Hoechst staining, and (2) increased mossy fibre sprouting, restricted to the stratum oriens of dorsal hippocampus, assessed by Timm's staining. Rats from the same cohorts displayed (3) deficits in non-spatial working memory, assessed by a novel object recognition task, and (4) increased anxiety, assessed by an elevated plus-maze test when examined at the age of 90 days. Nicotinamide prevented the effects elicited by perinatal asphyxia on apoptosis, working memory, and anxiety.
Morales
Paola
P
Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, PO Box 70,000, Santiago 7, Chile. pmorales@med.uchile.cl
Simola
Nicola
N
Bustamante
Diego
D
Lisboa
Francisco
F
Fiedler
Jenny
J
Gebicke-Haerter
Peter J
PJ
Morelli
Micaela
M
Tasker
R Andrew
RA
Herrera-Marschitz
Mario
M
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D049188:Prenatal Injuries / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D009536:Niacinamide