Neonatal handling impairs spatial memory and leads to altered nitric oxide production and DNA breaks in a sex specific manner.

Early life events lead to behavioral and neurochemical changes in adulthood. The aim of this study is to verify the effects of neonatal handling on spatial memory, nitric oxide (NO) production, antioxidant enzymatic activities and DNA breaks in the hippocampus of male and female adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth). In adulthood they were subjected to a Morris water maze or used for biochemical evaluations. Female handled rats showed impairment in spatial learning. They also showed decreased NO production, while no effects were observed in these parameters in male rats. No effects were observed on the number of hippocampal NADPH diaphorase positive cells. In the Comet Assay, male handled rats showed increased DNA breaks index when compared to non-handled ones. We conclude that neonatal handling impairs learning performance in a sex-specific manner, what may be related to NO decreased levels.

Tactile stimulation and maternal separation prevent hippocampal damage in rats submitted to neonatal hypoxia-ischemia.

Unilateral neonatal hypoxia-ischemia causes important damage to the hippocampus of the hemisphere ipsilateral to carotid artery occlusion; two forms of neonatal handling, tactile stimulation and maternal separation for a short period, have been shown to produce functional/behavioral protection in distinct models of CNS challenge. In this paper we investigated whether neonatal handling could alter the hippocampal damage caused by neonatal hypoxia-ischemia (HI) in the Wistar rat. Pups at postnatal day 7, P7, received HI (8% O(2)-92% N(2)) for 90 min and were submitted to neonatal handling, tactile stimulation of maternal separation daily, from P8 to P21, for 10 min. On adulthood, hippocampal volume was analyzed by stereological techniques, along with measures of cortical thickness and hemispheric area at the level -3.30 mm from bregma. HI caused a reduction of volume of whole hippocampus, of Amon's horn and of dentate gyrus, with no effect on cortical and hemispheric measures; neonatal handling prevented such effect. This is the first report showing that both tactile stimulation and neonatal handling exert a morphological neuroprotective action for HI-induced damage to the hippocampus.

Neonatal hypoxia-ischemia reduces ganglioside, phospholipid and cholesterol contents in the rat hippocampus.

Hypoxia-ischemia is a common cause of neonatal brain damage producing serious impact on cerebral maturation. This report demonstrates that rats submitted to hypoxia-ischemia present a marked decrease in hippocampal gangliosides, phospholipids and cholesterol contents as from 7 days after the injury. Although chromatographic profiles of the different ganglioside species (GM1, GD1a, GD1b, and GT1b) from the hippocampus of hypoxic-ischemic hippocampi groups (HI) were apparently unaffected, as compared with controls, there were quantitative absolute reductions in HI. The phospholipid patterns were altered in HI as from the 14th to the 30th day after the injury, where phosphatidylcholine (PC) quantities were higher than phosphatidylethanolamine (PE); additionally, the cardiolipin band was detected only in hippocampi of control adult rats. In general, the absolute quantities of phospholipids were lower in HI than in correspondent controls since 7th day after the injury. Considering that reported effects were maintained, we suggest they express a late biochemical response triggered by the neonatal hypoxic-ischemic episode; the consequences would be cell death and a delay on brain development, expressed by a reduction on synaptogenesis and myelinogenesis processes.

Perturbations in the thiol homeostasis following neonatal cerebral hypoxia-ischemia in rats.

Changes in the thiol/disulphide status in the neonatal rat brain were evaluated after an episode of neonatal hypoxia-ischemia (HI) in 7-day-old rats. The glutathione level decreased in the post-HI period. The lowest values (43-68%) were obtained 24 h post-HI. A statistically significant difference first appeared in hippocampus, immediately after the HI event, and only 12 h later in striatum and cortex. On the 7th day post-HI the glutathione content was completely recovered in the hippocampus and the striatum, and partially in the cortex. The glutathione loss could not be explained through its conversion to glutathione disulphide or to protein mixed disulphide (S-thiolation), whose values remained constant. Furthermore, we found a consistent decrease (20-30%) in protein thiols, which were not recovered after 7 days post-HI. Perturbations in protein thiols, along with the glutathione loss, may represent a valuable marker of immature rat brain damage.

Agmatine facilitates memory of an inhibitory avoidance task in adult rats.

Agmatine is a new putative neurotransmitter; however, the physiological role(s) of this endogenous released polyamine is still to be determined. We investigated its cognitive effect in an inhibitory avoidance task in adult rats. Agmatine (0.1, 1, 10, and 20 mg/kg) or saline was administered ip immediately after training or 1 h before testing. Posttraining injection of agmatine facilitated (p < 0.05) memory consolidation in this task; however pretest treatment showed no effect on retrieval (p > 0.05). We suggest that the facilitatory effect of agmatine on memory consolidation in inhibitory avoidance task might be mediated through the activation of the locus coeruleus.