Biomedical subjects

H Hallman

Publications and source records attributed to H Hallman.

At least 37 records · Page 2Linked to original sources

PubMed1984

Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse.

The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) on central monoamine neurons in mice was investigated using histo- and biochemical techniques. NMPTP (2 X 10 mg/kg i.v.) produced a rapid and long-lasting reduction (-30%) of striatal dopamine, while the dopamine levels were only transiently reduced in mesencephalon and frontal cortex. HVA and DOPAC were initially markedly reduced (-50 to -70%) in striatum while a marked recovery was found in the chronic stage. NMPTP also induced a long-term reduction of noradrenaline in striatum and frontal cortex while 5-hydroxytryptamine and 5-HIAA levels were essentially unaltered. The data indicate a neurotoxic action of NMPTP on both dopamine and noradrenaline nerve terminals in mouse brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1984

Effects of GM1 ganglioside on developing and mature serotonin and noradrenaline neurons lesioned by selective neurotoxins.

The effect of exogenous GM1 ganglioside on selective neurotoxin-induced lesions of serotonin (5-HT) and noradrenaline (NA) neurons in both the central and peripheral nervous systems has been investigated in developing and adult rats and mice by employing neuro- and histochemical techniques. 5,7-Dihydroxytryptamine (5,7-HT) was used to lesion 5-HT neurons, and 6-hydroxydopamine (6-OH-DA) was used to lesion NA neurons. In most lesion models investigated the neurotoxin causes primarily an axonal nerve terminal damage without notably affecting the perikarya. There was no evidence indicating that GM1 interferes with the primary and direct neurodegenerative actions of 5,7-HT or 6-OH-DA on 5-HT and NA nerve terminals, respectively. In all lesion models GM1 had in the chronic stage a counteracting effect on the neurotoxin-induced nerve terminal lesion or enhanced regrowth. The present results are compatible with the view that GM1 has a regrowth-stimulating effect and/or protective actions against secondary retrograde degeneration following the initial nerve terminal lesion induced by the neurotoxin.

5,7-Dihydroxytryptamine↗

PubMed1984

Effects of the noradrenaline neurotoxin DSP 4 on monoamine neurons and their transmitter turnover in rat CNS.

Regional effects of DSP 4 on monoamine neurons have been analyzed by chemical assay of endogenous monoamines and their metabolites in rat CNS. The results confirmed that the neurotoxic action of DSP 4 is predominantly on noradrenaline nerve terminal projections originating from locus coeruleus, with the most marked effects on terminal fields localized most distant from the noradrenaline perikarya. DSP 4 treatment (10 days) caused no alteration of the regional DA levels, except in cingulate cortex, where a moderate increase (+40%) was observed, possibly at least partially related to a sprouting of dopamine nerve terminals following the noradrenaline denervation. 5-hydroxytryptamine levels were generally unaltered after DSP 4, except for an about 10-25% reduction in cerebral cortex and hippocampus. There was with time a certain noradrenaline recovery, most likely related to regeneration of noradrenaline nerve terminals, although this process was relatively slow (months). Analysis of catecholamine decline after tyrosine hydroxylase inhibition and metabolite/monoamine ratios, as indices for transmitter utilization rate, indicated an increased noradrenaline turnover in terminals spared by DSP 4, while dopamine turnover appeared to be reduced in many regions (i.a. cerebral cortex, striatum, accumbens, olfactory tubercle and spinal cord), most pronounced in cingulate cortex. The results indicate that noradrenaline neurons have a facilitatory action on dopamine neurons. The DSP 4 treatment did not cause any significant effect on 5-hydroxytryptamine turnover in any of the individual regions analyzed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Effect of GM1 ganglioside on neonatally neurotoxin induced degeneration of serotonin neurons in the rat brain.

The effect of exogenous GM1 ganglioside on the 5,7-dihydroxytryptamine (5,7-HT; a selective serotonin neurotoxin) induced alteration of the postnatal development of central 5-hydroxytryptamine (5-HT; serotonin) neurons has been investigated using neuro-chemical and immunocytochemical techniques. Neonatal 5,7-HT (50 mg/kg s.c.) treatment is known to lead to a marked and a permanent degeneration of distant 5-HT nerve terminal projections (e.g. in cerebral cortex, hippocampus and spinal cord), while projections close to the 5-HT perikarya in the mesencephalon and pons-medulla increase their nerve density. These regional alterations are reflected by decreases and increases, respectively, of endogenous 5-HT, [3H]5-HT uptake in vitro and number of 5-HT nerve terminals demonstrated by immunocytochemistry. Treatment of newborn rats with GM1 (4 X 30 mg/kg s.c.; 24 h interval) had no significant effect on the postnatal development of 5-HT neurons. GM1 administration had furthermore no effect on the 5,7-HT induced alteration of the regional 5-HT levels and [3H]5-HT uptake in the cerebral cortex acutely, indicating that GM1 did not significantly interfere with the primary neurodegenerative actions of 5,7-HT. At the age of 1 month a clear counteracting effect of GM1 was observed, in particular of the 5,7-HT induced 5-HT denervations. The 5-HT levels in the frontal and occipital cortex were reduced to 25 and 20% of control after 5,7-HT alone, while these values were 70 and 40%, respectively, after 5,7-HT and GM1 treatment. A similar antagonizing effect of GM1 was found in the frontal cortex when measuring [3H]5-HT uptake. GM1 treatment also caused a minor reduction of the 5,7-HT induced increase of the 5-HT levels in striatum and mesencephalon. Quantitation of 5-HT nerve terminal density in sections processed for 5-HT immunocytochemistry using an automatic image analysis system showed markedly more nerve terminals in the frontal and occipital cortex after 5,7-HT + GM1 compared to 5,7-HT treatment alone. Minor counteracting effects of GM1 were noted in the hippocampus and spinal cord (thoracic-lumbar) as evaluated by chemical 5-HT assay, although substantial counteracting effects were observed locally in these areas by quantitative immunocytochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1984

Monoamine neurotransmitter metabolism in microencephalic rat brain after prenatal methylazoxymethanol treatment.

Administration of methylazoxymethanol (MAM) in the fetal stage leads to forebrain microencephaly with a severe atrophy in cerebral cortex, striatum, and hippocampus. The concentration of endogenous monoamines was markedly increased in the atrophic regions while total amount was largely unchanged. Striatal dopamine and cortical noradrenaline nerve terminals from MAM treated animals showed unaltered sedimentation properties in a sucrose density gradient and were estimated to have normal transmitter levels. gamma-Butyrolactone induced increase in dopamine levels and its counteraction by apomorphine was essentially unaltered after MAM. These data give further support for the view that the monoamine nerve terminal fields develop to their normal size in the atrophic regions leading to a hyperinnervation. Analysis of monoamine metabolite levels, increase of monoamines after monoamine oxidase inhibition, and disappearance of catecholamines after tyrosine hydroxylase inhibition were conducted to obtain information on monoamine turnover. The results indicated an essentially unaltered, or a small reduction of, monoamine turnover in the atrophic regions when calculated per monoamine nerve terminal, while increased when calculated per unit weight of the tissue.

Abnormalities, Drug-Induced↗

PubMed1984

Neurochemical studies on central dopamine neurons--regional characterization of dopamine turnover.

A simple and rapid dissection procedure was adopted to sample representative areas of the main meso-telencephalic dopaminergic (DA) neuron systems (nigrostriatal and meso-limbic-cortical) in the rat CNS. The object was to explore nerve terminal fields, cell body groups and dendrites, and to investigate the DA utilization rates in these regions. DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as well as noradrenaline (NA) were determined by liquid chromatography with electrochemical detection. Selective NA denervation with the neurotoxin DSP4 did not significantly change the DA levels in any of the regions studied, showing that the main part of the DA analysed originated from DA neurons. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) resulted in a time-dependent, often multi-phasic, DA and NA depletion pattern that varied between different regions. Comparison between the rate of DA decline and DOPAC/DA or HVA/DA ratios (also indices for DA utilization) in the various regions showed that the initial rate of DA disappearance after H44/68 appeared to be the most relevant index of DA utilization. The most rapid initial DA decline after H44/68 was found in the cortical regions (frontal, cingulate, and entorhinal) and the cell body areas A9 and A10, in particular in the cingulate cortex (t1/2 approximately equal to 20 min), indicating a very rapid DA turnover in this region. DA disappearance was clearly slower in striatum (t1/2 approximately equal to 45 min) and the slowest rates were found in the olfactory tubercle and the nucleus accumbens (t1/2 approximately equal to 1.5-2 h). The DA disappearance (t1/2 approximately equal to 45 min) pattern in the dendritic area (substantia nigra, pars reticulata) suggested an axon-terminal like behaviour of the DA dendrites with respect to DA utilization. In general, the DA metabolite/DA ratios obtained for the various regions agreed closely with these results. The rate of NA disappearance after H44/68 was slower than that of DA in most regions. The most rapid NA decline was found in the cortical regions (t1/2 approximately equal to 1-2 h), while very slow in the A9 and A10 regions (t1/2 approximately equal to 3-5 h).

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Effect of substance P on the 5,7-dihydroxytryptamine induced alteration of the postnatal development of central serotonin neurons.

Systemic treatment with the serotonin neurotoxin 5,7-dihydroxytryptamine [5,7-HT]in the neonatal stage leads to a permanent alteration of the postnatal development of the serotonin neurons in rat brain with denervation of distant nerve terminal projections and hyperinnervation in regions close to the serotonin perikarya. Intracisternal administration of substance P was found to counteract both the denervation and the hyperinnervation, as evaluated by measuring endogenous serotonin levels and [3H]-serotonin uptake in vitro. Furthermore, substance P was found to potentiate the reduction of serotonin induced by tryptophan hydroxylase inhibition with alpha-propyldopacetamide, indicating that substance P can produce an increase in serotonin utilization and turnover. The results suggest that substance P has a degeneration preventing and/or regrowth stimulatory effect on damaged serotonin neurons during ontogeny.

5,7-Dihydroxytryptamine↗

PubMed1983

Effect of substance P on neonatally axotomized noradrenaline neurons in rat brain.

Transection (axotomy) of the dorsal tegmental noradrenaline bundle in the neonatal stage leads to a permanent degeneration of noradrenaline nerve terminal projections distal to the lesion (e.g. in the neocortex), while projections proximal to the lesion increase their nerve terminal density (e.g. in the cerebellum). These structural changes are reflected by marked reductions and elevations respectively of the endogenous noradrenaline levels, [3H]-noradrenaline uptake in vitro and nerve density as demonstrated by fluorescence histochemistry. Intracisternal administration of substance P after the transection did not alter these noradrenaline parameters in the neocortex, whereas dose-dependent and significant increases were found in the cerebellum and pons-medulla. The results indicate that substance P may have a growth-stimulatory effect on damaged locus coeruleus noradrenaline neurons in the CNS during ontogeny.

Animals↗

PubMed1982

Substance P counteracts neurotoxin damage on norepinephrine neurons in rat brain during ontogeny.

Systemic treatment of newborn rats with the catecholamine neurotoxin 6-hydroxydopamine alters the postnatal development of the central norepinephrine neurons. The changes are permanent and consist of denervation of distant nerve terminal projections (for example, cerebral cortex) and hyperinnervation of terminal areas close to the cell bodies (for example, cerebellum). Intracisternal injection of substance P counteracted both of these alterations. The results indicate that substance P may prevent degeneration of damaged norepinephrine neurons during ontogeny or may have a regrowth stimulatory action on these cells. Substance P might prove of use in the prevention or reduction of other types of neurodegenerative disease.

Animals↗

PubMed1982

Evidence for a neurotropic role of noradrenaline neurons in the postnatal development of rat cerebral cortex.

The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1-4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, and 80% reduction after three doses, and a 97-98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.

Aging↗

PubMed1982

Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat.

The effect of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenergic neurons in the rat has been investigated using neurochemical techniques. The results demonstrated a preferential effect of DSP4 on the locus coeruleus noradrenergic neuron system without any notable effects on the dopamine and adrenaline neurons and only a minor neurotoxic effect on the serotonin neurons. The effect of DSP4 on the serotonin neurons could be completely prevented by pretreatment with the uptake blocker zimelidine, without affecting the action of DSP4 on noradrenergic neurons. Neonatal DSP4 treatment systemically led to permanent depletions of noradrenaline in the cerebral cortex and spinal cord and marked increases of noradrenaline in the cerebellum and pons-medulla. These effects of DSP4 were dose-dependent and could be blocked by pretreatment with the noradrenaline uptake blocker desipramine. The alterations in endogenous noradrenaline levels were quantitatively similar to changes observed in [3H]noradrenaline uptake in slices in vitro. There were no significant changes of these noradrenergic parameters when analysing the whole CNS after neonatal DSP4 treatment, in spite of marked regional changes in both directions. Administration of DSP4 to rats of different ages produced acutely marked depletions of noradrenaline in all regions including the pons-medulla and the cerebellum at all developmental stages. Marked and permanent depletions of noradrenaline were found in the distant noradrenergic nerve terminal projections after treatment at all ages, whereas increases in noradrenaline levels in the pons-medulla and cerebellum were only observed in rats treated with DSP4 up to the age of 3-5 days, whereas a DSP4 administration in older rats led to substantial and permanent depletions of noradrenaline in both these regions. The results indicate that the alteration of the postnatal development of noradrenergic neurons after treatment of rats up to the age of 3-5 days is mainly related to a 'pruning effect' of DSP4, in which prevention of the development of distant nerve terminal projections causes an increased outgrowth of nerves in collateral systems spared by the neurotoxin. The results indicate that DSP4 may be a useful denervation tool for studying various aspects of noradrenergic neurotransmission of developing locus coeruleus neurons.

Amines↗

PubMed1982

Substance P modifies the 6-hydroxydopamine induced alteration of postnatal development of central noradrenaline neurons.

Systemic treatment of new-born rats with the catecholamine neurotoxin 6-hydroxydopamine leads to a permanent and selective alteration of the postnatal development of the central noradrenaline neurons, in particular of the locus coeruleus system. The changes involve a pronounced and permanent degeneration of distant nerve terminal projections (e.g. in the cerebral cortex and spinal cord) and a hyperinnervation of regions close to the noradrenaline perikarya (e.g. in the cerebellum and pons-medulla). Substance P administered intracisternally was found to counteract significantly both the 6-hydroxydopamine-induced denervation and hyperinnervation, as monitored by measuring endogenous noradrenaline levels and [3H]noradrenaline uptake in vitro. The counteracting effect of substance P disclosed a clear dose-response relationship and was most effective when injected on postnatal days one and two, while practically no effects were observed after injection on postnatal days three and four. Substance P treatment alone of new-born rats had no effect on the postnatal development of the regional monoamine levels. Binding studies employing radioligand technique showed substance P treatment to abolish the 6-hydroxydopamine-induced increase in beta-receptor binding in the frontal cortex, suggesting the 'spared' noradrenaline terminals to be functionally active. Substance P was shown to increase the utilization of noradrenaline in the neonatal stage. The results indicate that the counteracting effect of substance P may be due to a prevention of degeneration, growth stimulation and/or trophic influences on central noradrenaline neurons, possibly related to an excitatory effect of substance P on noradrenaline neurons.

Animals↗

PubMed1982

Effects of morphine on the 6-hydroxydopamine induced changes of the postnatal development of central noradrenaline neurons.

Neonatal treatment with the catecholamine neurotoxin 6-hydroxydopamine (6-OH-DA) leads to permanent noradrenaline (NA) denervations of distant projections (e.g. in the neocortex) with a concomitant NA hyperinnervation in regions close to the perikarya (e.g. in the cerebellum) a "pruning effect' mainly affecting the locus coeruleus NA neuron system. Morphine administration after 6-OH-DA produced a significant potentiation of the 6-OH-DA-induced NA depletion in the olfactory bulb, spinal cord, frontal and occipital cortex, with a tendency for NA to increase in the mesencephalon, pons-medulla and cerebellum, when analysed in the adult stage. Morphine treatment alone had no effects on the NA levels in any region studied. Morphine was found to counteract the NA depletion induced by tyrosine hydroxylase inhibition in neonate rats, indicating that morphine reduces NA turnover. The present results are compatible with the view that morphine potentiates the 6-OH-DA-induced degeneration of NA nerve terminals, possibly related to the inhibitory action on NA neurons.

Animals↗

PubMed1982

Response of central monoamine neurons following an early neurotoxic lesion.

Systemic treatment with the selective monoamine neurotoxins 6-hydroxydopamine (6-OH-DA), N-(2-chloroethyl)N-ethyl-2-bromobenzylamine (DSP4) or 5,7-dihydroxytryptamine (5,7-HT) in the neonatal stage produces marked and permanent alterations of the postnatal development of central noradrenaline (NA) and 5-hydroxytryptamine (5-HT) neurons. 6-OH-DA and DSP4 act preferentially on NA neurons, in particular on the locus coeruleus system, whereas 5,7-HT acts on 5-HT neurons. The neurotoxin treatment leads to pronounced denervations of distant nerve terminal projections while innervation areas close to the cell bodies become hyperinnervated. The total number of monoamine nerve terminals developed in the CNS after the neurotoxin treatment is approximately unchanged. A surgical lesion of NA and 5-HT axons in the neonatal stage causes similar changes compared to a neonatal neurotoxin treatment. The postsynaptic monoamine receptors appear to develop independently of the presynaptic nerve terminals, although the transmitter availability at the receptors is able to regulate the number of receptors (up and down regulation). The transmitter turnover is increased in terminals spared by the neurotoxin in denervated areas, while decreased in hyperinnervated regions. The alterations in receptor density and transmitter turnover may represent compensatory mechanisms. Substance P has a counteracting effect while morphine has a potentiating effect on the 6-OH-DA-induced NA denervation and hyperinnervation, indicating that the functional state of the neuron may modulate the final outcome of a neonatal 6-OH-DA treatment. The results indicate that the altered development of central monoamine neurons following a neonatal monoamine neurotoxin treatment or axotomy is mainly related to a 'pruning effect', i.e. the prevention of the development of one axonal branch leads to a proliferative growth response in intact branches.

Animals↗

PubMed1981

DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine)--a useful denervation tool for central and peripheral noradrenaline neurons.

The effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on monoamine neurons was studied in mice and rats. In mice DSP4 produced acutely a marked reduction of endogenous noradrenaline (NA), [3H]NA uptake and nerve density of the adrenergic nerves in the iris and atrium. Pronounced accumulations of NA were observed in non-terminal axons, which is a degenerative sign, while no changes were found in the NA cell bodies. A marked recovery of all parameters analysed was found as soon as 1 week after DSP4. In the mouse CNS, however, there was a marked and long-lasting NA reduction, especially in the cerebral and cerebellar cortex and spinal cord, leaving dopamine (DA) and serotonin (5-HT) neurons apparently unaffected. Administration of DSP4 to adult rats produced regional changes in the NA levels of the CNS were similar to those observed in the mouse. There were no indications of DSP4 affecting dopamine and adrenaline neurons in rat CNS, although a minor 5-HT depleting effect was noted. DSP4 treatment resulted in an increase in beta-adrenoceptor binding in vitro to homogenates from the cerebral cortex, using [3H]dihydroalprenolol as radioligand. Treatment of newborn rats with DSP4 caused permanent NA disappearance in the cerebral cortex and spinal cord, whereas marked NA increases were found in the pons-medulla and cerebellum. Administration of DSP4 to pregnant rats (gestation day 15) led to a marked and permanent NA depletion in the cerebral cortex and spinal cord in the offspring. The results support the view that DSP4 can produce an acute and relatively selective degeneration of NA nerve terminals in the rat and mouse. The results furthermore indicate that DSP4 (systemically administered) causes a preferential degeneration of NA nerve terminal projections originating from the locus coeruleus in the CNS. Since DSP4 can pass both the blood-brain and blood-placenta barrier and appears to have potent neurotoxic actions on NA neurons, DSP4 may serve as a useful denervation tool for the analysis of NA transmitter functions, particularly in the CNS of both adult and developing animals.

Amines↗

PubMed1981

Effects of prenatal methylazoxymethanol treatment on the development of central monoamine neurons.

The effects of prenatal treatment with the antimitotic agent methylazoxymethanol (MAM; 25 mg/kg i.v., gestation day 15) on the development of monoamine neurons and their receptors have been investigated by neurochemical techniques. The MAM treatment led to a forebrain microencephaly with an approximately 50% weight reduction of the cerebral cortex and hippocampus, 30% of the striatum while the other CNS regions were reduced by about 5-15%. Endogenous noradrenaline (NA) dopamine (DA) and 5-hydroxytryptamine (5-HT) concentrations in the cerebral cortex and hippocampus were increased by about 100% and to a similar extent for all amines, whereas the total amine content in each brain region analyzed was more or less unchanged after MAM treatment. The DA concentration in the striatum was increased by 40% without any change in the total DA content. The subcellular distribution of NA and DA in the cerebral cortex and striatum was similar in MAM-treated and control rats. The effect of the NA denervation agent DSP4 was identical in MAM-treated and controls, showing very pronounced NA reductions in the cerebral cortex, hippocampus, cerebellum and the spinal cord, while the DA levels in various brain regions were not or only to a minor degree affected. Analysis of [3H]NA and [3H]5-HT uptake in slices from the cerebral cortex in vitro, demonstrated an approximate doubling of the uptake (calculated per weight) for both amines after MAM, while total uptake was not notably changed. MAM treatment also led to a significant reduction of the in vitro binding of various radioligands for monoamine (alpha, beta, 5-HT) receptors. The most pronounced reduction was observed for beta-receptors. Administration of a tyrosine-hydroxylase (alpha-methyl-p-tyrosine) or a tryptophan hydroxylase (alpha-propyldopacetamide) inhibitor led to marked NA/DA and 5-HT reductions after MAM in all regions analyzed, indicating that the monoamine neurons are active in synthesizing and releasing their neurotransmitter. The results suggest that MAM treatment leads to a monoamine hyperinnervation in the atrophic regions without markedly changing the total number of monoamine nerve terminals. All the monoamine nerves appear to develop independent of the formation of the post-synaptic receptors. The results imply that monoamine neurons in the CNS are strictly programmed to produce a certain quantity of nerve terminal arborizations in regions they innervate during the development relatively independent of the effector cells, pointing to a high degree of intrinsic growth regulation.

Animals↗

PubMed1981

Noradrenaline and dopamine interaction in rat brain during development.

The effects of systemic treatment of newborn rats with the catecholamine neurotoxins 6-hydroxydopamine (6-OH-DA) or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the central dopamine (DA) and noradrenaline (NA) neurons were studied using neurochemical techniques. Both neurotoxins cause similar alterations of the postnatal development of the NA neurons with a pronounced NA denervation in the cerebral cortex and a NA hyperinnervation in the pons-medulla. The results did not show any neurotoxic action of neonatal 6-OH-DA or DSP4 treatment on the DA neurons. The tyrosine hydroxylase inhibition model was used to evaluate catecholamine turnover. The data showed a reduced DA turnover both in the cerebral cortex and striatum in young rats (12 days old) after neonatal 6-OH-DA or DSP4 treatment. After 6-OH-DA this effect could be blocked by pretreatment with the NA uptake blocker desipramine, which also prevented the 6-OH-DA induced alteration of the development of NA neurons. No clear-cut effect on DA turnover was seen in the adult stage after neonatal 6-OH-DA or DSP4, although a reduced DA turnover was observed in the cortex after an acute DSP4 treatment in adult rats. The results show that NA nerve terminals originating in the locus coeruleus NA neurons may be involved in regulating the functional activity of the DA nerve terminals both in the cerebral cortex and the striatum. This regulation appears to be facilitatory in nature and is present early in development.

Adrenergic Fibers↗

PubMed1980

Effects of neonatal nicotine administration on the postnatal development of central noradrenaline neurons.

The effects of neonatal nicotine and/or 6-hydroxydopamine (6-OH-DA) treatment on the postnatal development of central noradrenaline (NA) neurons have been investigated using neurochemical and histochemical techniques. Nicotine was found to produce an increase of 3H-NA uptake and endogenous NA in the cerebral cortex and pons-medulla, which was most pronounced at the age of one week. These parameters were normalized in the adult stage. Neonatal nicotine treatment was also found to partially counteract the 6-OH-DA induced alteraton of the development of the locus coeruleus NA system. The NA denervation produced by 6-OH-DA in the cerebral cortex and the spinal cord was thus counteracted by nicotine treatment. The results suggest that neonatal nicotine administration has a growth stimulatory effect on the early postnatal development of central NA neurons.

Animals↗