Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats

Abstract

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.

Spontaneous object recognition and its relevance to schizophrenia: a review of findings from pharmacological, genetic, lesion and developmental rodent models

“…In rodents, both perinatal asphyxia and postnatal hypoxia impaired SOR. Asphyxia on the last day of gestation led to impaired SOR with a 1-h delay when the animals were tested as adults (Simola et al 2008;Morales et al 2010). Performance was intact with a 15-min delay, arguing against a non-mnemonic explanation for the deficit (Simola et al 2008).…”

Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

“…The perinatal asphyxia model, intra-uterus oxygen deprivation, causes non-spatial working memory deficits, increased apoptosis in the whole hippocampus at 30-45 days, increased mossy fiber sprouting in dorsal hippocampus and increased anxiety behavior at 90 days (Morales, Simola et al 2010). In the neonatal anoxia model, used in the present research, acute hippocampal cell death, spatial memory and learning deficits in adult rats were observed after oxygen deprivation (Takada, dos Santos Haemmerle et al 2015).…”

Long lasting cerebellar alterations after perinatal asphyxia in rats

“…Behavioural test were already made using this perinatal asphyxia model by several researcher groups (Hoeger et al, 2006;Loidl et al, 2000;Morales et al, 2010;Strackx et al, 2010;Van de Berg et al, 2003), etc.) including our group (Galeano et al, 2011).…”