Impact of perinatal asphyxia on the GABAergic and locomotor system

Berg, Wilma D. J. van de; Kwaijtaal, Martijn; Louw, A.J.A. de; Lissone, N.P.A; Schmitz, Christoph; Faull, Richard L.M.; Blokland, Arjan; Blanco, Carlos E.; Steinbusch, Harry W.M.

doi:10.1016/s0306-4522(02)00787-x

Cited by 57 publications

(44 citation statements)

References 70 publications

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“…These receptors are localized mostly extrasynaptically. It was also found that perinatal asphyxia does not induce changes in the density and distribution of GABA А receptors [38]. Thus, if the amount of GABA released from hippocampal terminals after stimulation of exocytosis in animals subjected to hypoxia remains unchanged, and the rate of re-uptake becomes significantly decreased, such a situation will provide a higher efficiency of tonic inhibition and, consequently, will help to maintain the balance between the excitatory and inhibitory processes under conditions of intensification of excitatory effects.…”

Section: Discussionmentioning

confidence: 96%

Transmembrane Transport and Release of GABA in the Brain of Rats Subjected to Postnatal Hypoxia

et al. 2008

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We studied the effects of early postnatal hypoxia on the efficiency of active GABA transport through the plasma membrane of synaptic terminals (synaptosomes) isolated from the cerebral cortex, hippocampus, and thalamus of rats and on non-stimulated and Ca 2+ -stimulated GABA release. The state of hypoxia was induced by exposure of 10-to 12-day-old rats to a respiratory medium with low O 2 content (4% О 2 and 96% N 2 ) for 12 min (up to the initiation of clonico-tonic seizures). Animals were taken in the experiment 8 to 9 weeks after an episode of hypoxic stress. The intensity of transmembrane transport of GABA was estimated according to accumulation of [ 3 Н]GABA in a coarse synaptosomal fraction. The process was characterized by calculation of the Michaelis constant K m and also of the initial (within the 1st min) and maximum rates of accumulation of [ 3 Н]GABA. The means of the initial rate of [ 3 Н]GABA accumulation in preparations from the thalamus, cortex, and hippocampus were 205.5 ± 8.8, 266.2 ± 29.6, and 302.3 ± 31.2 pmol/min ⋅ mg protein, respectively. Hypoxic stress influenced the rates of accumulation of [ 3 Н]GABA in synaptic terminals from the cortex and hippocampus but not in those from the thalamus. According to the characteristics of the response to hypoxic stress, all experimental animals could be classified into two groups. In some rats, accumulation of [ 3 Н]GABA in both cortical and hippocampal synaptosomes decreased insignificantly (by about 15%), while in other animals this parameter increased significantly (by nearly 50%) for the cortex and decreased by 21.5%, on average, for the hippocampus. The affinity of the transporter with respect to [ 3 Н]GABA in the cortex and hippocampus was nearly the same and showed no changes under the influence of hypoxia. The non-stimulated release of [ 3 Н]GABA after the influence of hypoxia increased in all structures, while the depolarization-induced Ca 2+ -dependent release of [ 3 Н]GABA was intensified only in synaptosomes from the cerebral cortex. The mechanisms of development of modifications of GABA-ergic processes under the influence of hypoxic stress in the course of the perinatal period are discussed.

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Section: Discussionmentioning

confidence: 96%

Transmembrane Transport and Release of GABA in the Brain of Rats Subjected to Postnatal Hypoxia

et al. 2008

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“…A model of intra-uterine perinatal asphyxia has been developed in pregnant rats, where global fetal hypoxia is induced by transient disruption of maternal uterine blood flow shortly before term [4,5] . However, due to the immaturity of the rat cerebral cortex at birth, relative to the newborn human infant, 1-week-old rodents are more commonly used to study hypoxia-induced brain injury [6] .…”

Section: Introductionmentioning

confidence: 99%

Behavioural Effects of Near-Term Acute Fetal Hypoxia in a Small Precocial Animal, the Spiny Mouse <i>(Acomys cahirinus)</i>

Ireland

Dickinson²,

Fleiss

et al. 2009

Neonatology

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We have previously developed a model of near-term intra-uterine hypoxia producing significant neonatal mortality (37%) in a small laboratory animal – the spiny mouse – which has precocial offspring at birth. The aim of the present study was to determine if this insult resulted in the appearance of behavioural abnormalities in those offspring which survived the hypoxic delivery. Behavioural tests assessed gait (using footprint patterns), motor coordination and balance on an accelerating rotarod, and spontaneous locomotion and exploration in an open field. We found that the near-term acute hypoxic episode produced a mild neurological deficit in the early postnatal period. In comparison to vaginally delivered controls, hypoxia pups were able to remain on the accelerating rotarod for significantly shorter durations on postnatal days 1–2, and in the open field they travelled significantly shorter distances, jumped less, and spent a greater percentage of time stationary on postnatal days 5 and 15. No changes were observed in gait. Unlike some rodent models of cerebral hypoxia-ischaemia, macroscopic examination of the brain on postnatal day 5 showed no gross cystic lesions, oedema or infarct. Future studies should be directed at identifying hypoxia-induced alterations in the function of specific brain regions, and assessing if maternal administration of neuroprotective agents can prevent against hypoxia-induced neurological deficits and brain damage that occur at birth.

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“…The mechanism involved in reelin reduction could be related to the preferential vulnerability of GABAergic neurons to excitotoxicity during the perinatal period [41]. It has been described that PA generates a reduction in GABAergic cells in the cortex [42] and striatum [41].…”

Section: Discussionmentioning

confidence: 99%

“…It has been described that PA generates a reduction in GABAergic cells in the cortex [42] and striatum [41]. During the perinatal period, the Cajal-Retzius cells disappear and a subpopulation of GABAergic neurons starts to secrete reelin around the second postnatal week [43].…”

Section: Discussionmentioning

confidence: 99%

Perinatal Asphyxia Reduces the Number of Reelin Neurons in the Prelimbic Cortex and Deteriorates Social Interaction in Rats

Vazquez

Peña²,

Rico³

et al. 2016

Dev Neurosci

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Obstetrical complications of perinatal asphyxia (PA) can often induce lesions that, in the long-term, manifest as schizophrenia. A deterioration of the medial prefrontal cortex (mPFC) and a reduction in the number of GABAergic neurons are commonly observed in the pathophysiology of schizophrenia. In this study, we investigated the link between PA, reelin and calbindin diminution and psychiatric diseases that involve social interaction deficits. This was achieved by observing the effect of 19 min of asphyxia on both subpopulations of GABAergic neurons. PA was produced by water immersion of fetus-containing uterus horns removed by cesarean section from ready-to-deliver rats. PA generated a significant and specific decrease in the number of reelin-secreting neurons in mPFC layer VI [F(2, 6) = 8.716, p = 0.016; PA vs. vaginal controls (VC), p = 0.03, and PA vs. cesarean controls (CC), p = 0.022]. This reduction reached approximately 60% on average. Changes in the percentage of reelin neurons including all the cortex layers did not achieve a significant outcome but a trend: CC % 10.61 ± 1.34; PA % 8.64 ± 1.71 [F(2, 6) = 1.299, p = 0.33]. In the case of calbindin, there was a significant decrease in cell density in the PA group [2-way repeated-measures ANOVA, F(1, 4) = 13.03, p = 0.0226]. The multiple-comparisons test showed significant differences in the superficial aspect of layer II (Sidak test for multiple comparisons CC vs. PA at 200 µm: p = 0.003). A small, but significant difference could be seen when the distance from the pia mater to the start of layer VI was analyzed (CC mean ± SEM = 768.9 ± 8.382; PA mean ± SEM = 669.3 ± 17.75; p = 0.036). Rats exposed to PA showed deterioration in social interactions, which manifested as a decrease in play soliciting. In this model, which involved severe/moderate asphyxia, we did not find significant changes in locomotive activity or anxiety indicators in the open field task. The loss of reelin neurons could be conducive to the shrinkage of the prelimbic cortex through the reduction in neuropil and the deterioration of the function of this structure.

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Impact of perinatal asphyxia on the GABAergic and locomotor system

Cited by 57 publications

References 70 publications

Transmembrane Transport and Release of GABA in the Brain of Rats Subjected to Postnatal Hypoxia

Transmembrane Transport and Release of GABA in the Brain of Rats Subjected to Postnatal Hypoxia

Behavioural Effects of Near-Term Acute Fetal Hypoxia in a Small Precocial Animal, the Spiny Mouse <i>(Acomys cahirinus)</i>

Perinatal Asphyxia Reduces the Number of Reelin Neurons in the Prelimbic Cortex and Deteriorates Social Interaction in Rats

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