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

2015 ◽  
Vol 38 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Marianna A. Pagida ◽  
Anastasia E. Konstantinidou ◽  
Anna Korelidou ◽  
Dimitra Katsika ◽  
Effrosini Tsekoura ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Locus Coeruleus ◽  
Dopaminergic Neurons ◽  
Ischemic Injury ◽  
Selective Vulnerability ◽  
Noradrenergic Neurons ◽  
Critical Periods ◽  
Human Neonate ◽  
Almost All ◽  
Hypoxic Ischemic Injury

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.

scholarly journals Cellular localization of tyrosine hydroxylase by immunohistochemistry.

1975 ◽  
Vol 23 (1) ◽  
pp. 1-12 ◽  
Author(s):  
V M Pickel ◽  
T H Joh ◽  
P M Field ◽  
C G Becker ◽  
D J Reis
Keyword(s):  
Tyrosine Hydroxylase ◽  
Dopaminergic Neurons ◽  
Chromaffin Cells ◽  
Cellular Localization ◽  
Dopaminergic System ◽  
Noradrenergic Neurons ◽  
Dopamine Beta Hydroxylase ◽  
The Central Nervous System ◽  
Cervical Ganglia ◽  
Large Neurons

The enzyme tyrosine hydroxylase (TH) was immunohistochemically localized by the peroxidase-antiperoxidase method in rat to chromaffin cells of the adrenal medulla, large neurons and small darkly staining cells of the superior cervical ganglia and noradrenergic and dopaminergic neurons in brain. As compared with the conjugated peroxidase or immunofluorescence techniques, the peroxidase-antiperoxidase method gave the most selective and specific cytoplasmic localization of TH antisera in every tissue examined. The peroxidase staining with the TH antisera was more intense in dopaminergic than in noradrenergic neurons of the central nervous system. While TH was visualized in cell bodies of both dopaminergic and noradrenergic neurons, it could only be detected in axons and terminals in the dopaminergic system. The perikarya of noradrenergic neurons could be distinguished from dopaminergic neurons by the immunohistochemical demonstration of the enzyme dopamine-beta-hydroxylase only in the former.

Distribution and origin of the catecholaminergic innervation in the amphibian mesencephalic tectum

2002 ◽  
Vol 19 (3) ◽  
pp. 321-333 ◽  
Author(s):  
CRISTINA SÁNCHEZ-CAMACHO ◽  
OSCAR MARÍN ◽  
AGUSTÍN GONZÁLEZ
Keyword(s):  
Tyrosine Hydroxylase ◽  
Locus Coeruleus ◽  
Optic Tectum ◽  
Dopaminergic Neurons ◽  
Sensory Information ◽  
Amphibian Species ◽  
Normal Behavior ◽  
Pleurodeles Waltl ◽  
Catecholaminergic Innervation ◽  
Catecholaminergic Cell

The mesencephalic tectum plays a prominent role in integrating both visual and multimodal sensory information essential for normal behavior in amphibians. Activity in the mesencephalic tectum is thought to be modulated by the influence of distinct neurochemical inputs, including the catecholaminergic and the cholinergic systems. In the present study, we have investigated the distribution and the origin of the catecholaminergic innervation of the mesencephalic tectum in two amphibian species, the anuran Rana perezi and the urodele Pleurodeles waltl. Immunohistochemistry for dopamine and two enzymes required for the synthesis of catecholamines, tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH), revealed a complex pattern of catecholaminergic (CA) innervation in the anuran and urodele mesencephalic tectum. Dopaminergic fibers were primarily present in deep tectal layers, whereas noradrenergic (DBH immunoreactive) fibers predominated in superficial layers. Catecholaminergic cell bodies were never observed within the tectum. To determine the origin of this innervation, applications of retrograde tracers into the optic tectum were combined with immunohistochemistry for TH. Results from these experiments demonstrate that dopaminergic neurons in the suprachiasmatic and juxtacommissural nuclei (in Rana) or in the nucleus pretectalis (in Pleurodeles), together with noradrenergic cells of the locus coeruleus, are the sources of CA input to the amphibian mesencephalic tectum. The present results suggest that similar CA modulatory inputs are present in the mesecencephalic tectum of both anurans and urodeles.

scholarly journals The Norepinephrine Metabolite DOPEGAL Confers Locus Coeruleus Tau Vulnerability and Propagation via Asparagine Endopeptidase

2019 ◽  
Author(s):  
Seong Su Kang ◽  
Xia Liu ◽  
Eun Hee Ahn ◽  
Jie Xiang ◽  
Fredric P. Manfredsson ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Locus Coeruleus ◽  
Selective Vulnerability ◽  
Monoamine Oxidase A ◽  
Noradrenergic Neurons ◽  
Tau Pathology ◽  
Intact Cells ◽  
Tau Aggregation ◽  
The Brain

AbstractAberrant Tau inclusions in the locus coeruleus (LC) are the earliest detectable Alzheimer’s disease (AD)-like neuropathology in the human brain; however, why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in disease and whether the LC might seed the stereotypical spread of Tau pathology to the rest of the brain remain unclear. Here we show that 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which is produced exclusively in noradrenergic neurons by monoamine oxidase A (MAO-A) metabolism of norepinephrine (NE), activates asparagine endopeptidase (AEP) that cleaves Tau at residue N368 into aggregation- and propagation-prone forms, thereby leading to LC degeneration and the spread of Tau pathology. DOPEGAL triggers AEP-cleaved Tau aggregationin vitroand in intact cells, resulting in LC neurotoxicity and propagation of pathology to the forebrain. Thus, our findings reveal a novel molecular mechanism underlying the selective vulnerability of LC neurons in AD.

scholarly journals Early Thalamic Injury After Resuscitation From Severe Asphyxial Cardiac Arrest in Developing Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Hoai T. Ton ◽  
Katherine Raffensperger ◽  
Michael Shoykhet
Keyword(s):  
Cardiac Arrest ◽  
Microglial Activation ◽  
Neuronal Degeneration ◽  
Ischemic Injury ◽  
Selective Vulnerability ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Severity Of Injury ◽  
Hypoxic Ischemic Injury ◽  
Asphyxial Cardiac Arrest

Children who survive cardiac arrest often develop debilitating sensorimotor and cognitive deficits. In animal models of cardiac arrest, delayed neuronal death in the hippocampal CA1 region has served as a fruitful paradigm for investigating mechanisms of injury and neuroprotection. Cardiac arrest in humans, however, is more prolonged than in most experimental models. Consequently, neurologic deficits in cardiac arrest survivors arise from injury not solely to CA1 but to multiple vulnerable brain structures. Here, we develop a rat model of prolonged pediatric asphyxial cardiac arrest and resuscitation, which better approximates arrest characteristics and injury severity in children. Using this model, we characterize features of microglial activation and neuronal degeneration in the thalamus 24 h after resuscitation from 11 and 12 min long cardiac arrest. In addition, we test the effect of mild hypothermia to 34°C for 8 h after 12.5 min of arrest. Microglial activation and neuronal degeneration are most prominent in the thalamic Reticular Nucleus (nRT). The severity of injury increases with increasing arrest duration, leading to frank loss of nRT neurons at longer arrest times. Hypothermia does not prevent nRT injury. Interestingly, injury occurs selectively in intermediate and posterior nRT segments while sparing the anterior segment. Since all nRT segments consist exclusively of GABA-ergic neurons, we asked if GABA-ergic neurons in general are more susceptible to hypoxic-ischemic injury. Surprisingly, cortical GABA-ergic neurons, like their counterparts in the anterior nRT segment, do not degenerate in this model. Hence, we propose that GABA-ergic identity alone is not sufficient to explain selective vulnerability of intermediate and posterior nRT neurons to hypoxic-ischemic injury after cardiac arrest and resuscitation. Our current findings align the animal model of pediatric cardiac arrest with human data and suggest novel mechanisms of selective vulnerability to hypoxic-ischemic injury among thalamic GABA-ergic neurons.

scholarly journals Noradrenergic But Not Dopaminergic Neurons Signal Task State Changes and Predict Reengagement After a Failure

2020 ◽  
Vol 30 (9) ◽  
pp. 4979-4994
Author(s):  
Caroline I Jahn ◽  
Chiara Varazzani ◽  
Jérôme Sallet ◽  
Mark E Walton ◽  
Sébastien Bouret
Keyword(s):  
Locus Coeruleus ◽  
Dopaminergic Neurons ◽  
Noradrenergic Neurons ◽  
Task Condition ◽  
Catecholaminergic Neurons ◽  
Subsequent Trial ◽  
Midbrain Dopaminergic Neurons ◽  
State Changes ◽  
Reward Availability

Abstract The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behavior. Both noradrenergic and dopaminergic neurons respond to cues predicting reward availability and novelty. However, even though both are thought to be involved in motivating actions, their roles in motivation have seldom been directly compared. We therefore examined the activity of putative noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with engagement with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) more strongly activated in nonrepeated trials, when cues indicated a new task condition. This suggests that while both catecholaminergic neurons are involved in promoting action, noradrenergic neurons are sensitive to task state changes, and their influence on behavior extends beyond the immediately rewarded action.

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