Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

Strackx, Eveline; Hove, Daniël L.A. van den; Steinbusch, Harry; Prickaerts, Jos; Vles, Johan S.H.; Blanco, Carlos E.; Steinbusch, Harry W.M.; Gavilanes, Antonio W. D.

doi:10.1159/000155218

Cited by 16 publications

(26 citation statements)

References 98 publications

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“…Since the LC may be involved in the arousal of the newborn and the first breaths after birth [81], decreased LC activity - caused by severe perinatal hypoxic/ischemic events - might be the underlying cause for the reduced alertness observed in severe hypoxic neonates [82]. In view also of experimental evidence that perinatal hypoxia causes a reduction of noradrenaline LC [20] as well as serotonergic raphe neurons [21,83] that persists into adulthood, we suggest that early dysregulation of monoaminergic neurotransmission in critical periods of brain development in humans, in combination with genetic susceptibility, may predispose the survivors of perinatal hypoxia to psychiatric and/or neurological disorders, such as major depression, Parkinson's disease and Alzheimer's disease, later in life [1,12,84]. …”

Section: Discussionmentioning

confidence: 99%

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

Pagida¹,

Konstantinidou²,

Korelidou³

et al. 2015

Dev Neurosci

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We have previously shown that perinatal hypoxic/ischemic injury (HII) may cause selective vulnerability of the mesencephalic dopaminergic neurons of human neonate. In the present study, we investigated the effect of perinatal HII on the noradrenergic neurons of the locus coeruleus (LC) of the same sample. We studied immunohistochemically the expression of tyrosine hydroxylase (TH, first limiting enzyme for catecholamine synthesis) in LC neurons of 15 autopsied infants (brains collected from the Greek Brain Bank) in relation to the neuropathological changes of acute or chronic HII of the neonatal brain. Our results showed that perinatal HII appears to affect the expression of TH and the size of LC neurons of the human neonate. In subjects with neuropathological lesions consistent with abrupt/severe HII, intense TH immunoreactivity was found in almost all neurons of the LC. In most of the neonates with neuropathological changes of prolonged or older injury, however, reduction in cell size and a decrease or absence of TH staining were observed in the LC. Intense TH immunoreactivity was found in the LC of 3 infants of the latter group, who interestingly had a longer survival time and had been treated with anticonvulsant drugs. Based on our observations and in view of experimental evidence indicating that the reduction of TH-immunoreactive neurons occurring in the LC after perinatal hypoxic insults persists into adulthood, we suggest that a dysregulation of monoaminergic neurotransmission in critical periods of brain development in humans is likely to predispose the survivors of perinatal HII, in combination with genetic susceptibility, to psychiatric and/or neurological disorders later in life.

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Section: Discussionmentioning

confidence: 99%

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

Pagida¹,

Konstantinidou²,

Korelidou³

et al. 2015

Dev Neurosci

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“…Indeed, while a significant difference in the amount of grooming was observed at 4 days of age, there was no difference in the number of bouts of grooming between C-section-delivered and asphyxiated offspring at 28 days. A number of studies using rats subjected to perinatal hypoxia also indicate that offspring have increased anxiety levels, although these tests were done at a significantly older age (1-2 years of age) [27,28] , and other studies show reduced anxiety at 2 months of age [29] . It may be necessary to investigate anxiety more directly, using naïve animals in an open field, or protocols that provoke anxiety, such as the elevated-plus maze.…”

Section: Discussionmentioning

confidence: 99%

Neuropathology and Functional Deficits in a Model of Birth Asphyxia in the Precocial Spiny Mouse <i>(Acomys cahirinus)</i>

Hutton

Ratnayake²,

Shields

et al. 2009

Dev Neurosci

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Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at 37 days gestational age (term is 39 days). Brain histology was examined at 1 and 7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated offspring showed significant impairment in non-spatial memory and learning tasks, accompanied by central nervous system inflammation and increased apoptotic cell death but without the presence of large necrotic or cystic lesions.

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“…The pattern of the staining revealed densely stained small particles, reflecting hypermethylated DNA fragments (Brown et al, 2008; Hernandez-Blazquez et al, 2000). Threshold values were set in order to correct for background signal (Strackx et al, 2008). Surface area was defined as the percentage of the area delineated with a gray value below the background threshold.…”

Section: Methodsmentioning

confidence: 99%

Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction

Chouliaras

Hove

Kenis

et al. 2012

Neurobiology of Aging

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Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1–2 regions, which was prevented by CR but not by SOD1 overexpression. Moreover, positive correlations between 5-mC and Dnmt3a immunoreactivity were observed in the CA3 and CA1–2. These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging.

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Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

Cited by 16 publications

References 98 publications

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

Neuropathology and Functional Deficits in a Model of Birth Asphyxia in the Precocial Spiny Mouse <i>(Acomys cahirinus)</i>

Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction

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