Long-term changes in noradrenaline (NA) and dopamine (DA) contents of rat cerebellum following neonatal X-irradiation

Dopico, Alejandro M.; Zieher, Luis Marı́a; J, Mayo; Altschüller, Noe; López, Juan José; Jaim-Etcheverry, Guillermo

doi:10.1016/0197-0186(89)90081-8

Cited by 17 publications

(18 citation statements)

References 34 publications

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“…Our results confirm previous studies which showed that the exposure of neonatal rats to X-irradiation in a critical period of cerebellar cortex development (days 0-6 after birth) induces a long-term increase in the NA content of CE, without inducing long-term changes of NA levels in other terminal areas of the LC (Dopico et al, 1989a(Dopico et al, ,b, 1990. Since different brain regions (i.e., neocortex and CE) receive axonal collaterals from the same LC neurons (Steindler, 1981;Waterhouse et al, 1983;Loughlin et al, 1986), we suggested that this increase in cerebellar NA levels is probably target-dependent (Dopico et al, 1989a(Dopico et al, , 1990.…”

Section: Discussionsupporting

confidence: 82%

“…Since different brain regions (i.e., neocortex and CE) receive axonal collaterals from the same LC neurons (Steindler, 1981;Waterhouse et al, 1983;Loughlin et al, 1986), we suggested that this increase in cerebellar NA levels is probably target-dependent (Dopico et al, 1989a(Dopico et al, , 1990. The increased level of the neurotransmitter content reported here is accompanied by a dystonic syndrome, atrophy of CE, and characteristic abnormalities in the cytoarchitecture of the cerebellar cortex.…”

Section: Discussionmentioning

confidence: 99%

“…In previous works, we have shown that X-irradiation applied on the cephalic end of neonatal rats induces a dystonic syndrome, that can be observed even 390 d after exposure to ionizing radiation. The motor abnormalities coexist with a long-term increase in the noradrenaline (NA) content of adult cerebellum (CE), not found in other terminal fields of the locus coeruleus (LC), such as, the neocortex and the spinal cord (Dopico et al, 1989a;Dopico et al, 1990). Both the persistent increase in the cerebellar content of NA and the motor deficits are not found when X-irradiation is applied to adult rats, in which cerebellar connectivity has reached definitive patterns (Dopico et al, 1989a).…”

Section: Introductionmentioning

confidence: 99%

“…The motor abnormalities coexist with a long-term increase in the noradrenaline (NA) content of adult cerebellum (CE), not found in other terminal fields of the locus coeruleus (LC), such as, the neocortex and the spinal cord (Dopico et al, 1989a;Dopico et al, 1990). Both the persistent increase in the cerebellar content of NA and the motor deficits are not found when X-irradiation is applied to adult rats, in which cerebellar connectivity has reached definitive patterns (Dopico et al, 1989a). Furthermore, these abnormalities can only be evoked when X-rays are administered within a critical period of development, from 0 to 6 d postnatally (Dopico et al, 1989b).…”

Section: Introductionmentioning

confidence: 99%

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Increased activity of tyrosine hydroxylase in the cerebellum of the X-irradiated dystonic rat

Dopico

Rı́os

et al. 1990

Molecular and Chemical Neuropathology

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The exposure of the cephalic end of rats to repeated doses of X-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 +/- 4 ng/CE and 2.8 +/- 1.5 ng/CE, respectively) and X-irradiated rats (17.1 +/- 1 ng/CE and 8.3 +/- 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally X-irradiated animals when compared to age-matched controls (16.4 +/- 1.4 vs 6.32 +/- 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 +/- 23.8 vs 408.2 +/- 21.5 nmol CO2/h/CE, p less than 0.01 (controls and X-treated, respectively). These results suggest that X-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased activity of tyrosine hydroxylase in the cerebellum of the X-irradiated dystonic rat

Dopico

Rı́os

et al. 1990

Molecular and Chemical Neuropathology

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“…Previous studies have shown that the noradrenergic system, specifically the locus cocruleus, is susceptible to a variety of chemical and physical insults [41], But in the studies by Dopico ct al. (34], which exposed the whole head to X-irradiation, the cerebellum was the only brain region demonstrating an increase in NE. The absence of an increase in NE, except in the cerebellum, suggests that X-irradiation exposure has lit tle direct effect on the noradrenergic system or that these effects arc unique to the cerebellar NE terminals.…”

Section: Discussionmentioning

confidence: 99%

Noradrenergic Innervation of the External Granular Layer of the Rat following Low-Level X-Irradiation

Kunkler

Anderson²

1994

Dev Neurosci

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The distribution of the noradrenergic system within the rat cerebellar cortex following low-level X-irradiation was studied using tyrosine hydroxylase immunocytochemistry. X-Irradiation treatments consisted of 1, 3, or 5 successive daily doses beginning on postnatal day 1. When studied 24 h after the last exposure, a dense plexus of tyrosine hydroxylase-Iike immunoreactive (THIR) fibers, not found in age-matched controls, was observed in the reduced external granular layer (EGL) in each treatment group. At 10 days of age, the THIR fibers were found in association with the reconstituted cells of the premigratory zone of the EGL. The rapid and abnormal innervation of the EGL by the THIR fibers suggests that the noradrenergic system could play a role in the regeneration of this layer.

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Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-Irradiation at birth

Guelman

Zieher

Rı́os

et al. 1993

Molecular and Chemical Neuropathology

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We have studied the developmental time-course of changes in the noradrenaline (NA) content of cerebellum (CE), cytoarchitecture of the cerebellar cortex, and motor abnormalities induced by the exposure of the cephalic end of rats to a single dose (5 Gy) of X-irradiation immediately after birth. At all ages examined, i.e., from postnatal (PN) d 5 to 90, CE from exposed animals show a marked atrophy, with an agranular cortex that has lost its layered structure. Purkinje cells are scattered at all depths in the cortex, and their primary dendrite is randomly oriented. The motor syndrome includes dystonia-like movements, a fine tremor, and an ataxic gait. Being progressive, the abnormal movements are evident from PN d 10, and fully developed by d 30. On the other hand, no differences in cerebellar NA content between X-irradiated rats and age-matched nonirradiated controls were detected from PN d 5 to 60. However, at PN d 90 a significant increase in NA content of CE from exposed animals is found when compared to either age-matched controls (+36%, p < 0.01), or data from irradiated rats obtained at PN d 5 to 60 (p < 0.01). These results indicate a temporal dissociation between the motor and cytoarchitectural abnormalities and the increase in cerebellar NA content produced by a single dose of X-rays at birth. The late increase in cerebellar NA content might represent a compensatory response of noradrenergic terminals to an altered information flow out of the cerebellar cortex induced by the ionizing noxa.

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Long-term changes in noradrenaline (NA) and dopamine (DA) contents of rat cerebellum following neonatal X-irradiation

Cited by 17 publications

References 34 publications

Increased activity of tyrosine hydroxylase in the cerebellum of the X-irradiated dystonic rat

Increased activity of tyrosine hydroxylase in the cerebellum of the X-irradiated dystonic rat

Noradrenergic Innervation of the External Granular Layer of the Rat following Low-Level X-Irradiation

Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-Irradiation at birth

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