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PubMed1998

Islet cell autoimmunity in white and black children and adolescents with IDDM.

OBJECTIVE: To compare the frequency of islet cell antibodies (ICA) and antibodies to GAD65 and IA-2(ICA512) between black and white children and adolescents at the diagnosis of IDDM in a large consecutive series of cases from Children's Hospital of Pittsburgh. RESEARCH DESIGN AND METHODS: ICA and antibodies to GAD65 and IA-2 were measured in 437 white and black children and adolescents who were diagnosed with IDDM at < 19 years of age at Children's Hospital of Pittsburgh from January 1983 to December 1985, from January to December 1989, and from January 1996 to December 1997. RESULTS: The prevalence of ICA(H), GAD65, and IA-2 antibodies was significantly lower in blacks than whites at onset of the disease. In contrast, the prevalence of ICA(R) alone was higher in blacks. None of the antibodies were present in 12% of the blacks compared with 4% in whites. The same pattern was seen in both sexes. The prevalence of antibodies in white patients with onset of IDDM at <11 years of age was no different than in those who developed IDDM during adolescence. In contrast, black patients showed a significantly lower prevalence of almost all antibodies in the adolescent group. CONCLUSIONS: Black adolescents were more likely to not have antibodies, suggesting either that they have a nonautoimmune type of diabetes or that antibodies are not being detected by these assays.

Adolescent↗
PubMed1990

[Studies on monoamine metabolism in the rat brain with overdosage of manganese].

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.

Animals↗
PubMedDate not supplied

Dual-parameter model for prediction of type I diabetes mellitus.

The recent cloning and recombinant expression of novel islet autoantigens [glutamic acid decarboxylase (GAD) 65 and islet-cell autoantibody 512 (ICA512)] has made possible the determination of whether the quantitative expression of autoantibodies to these molecules is correlated with age of diabetes onset and rate of progression to diabetes, similar to insulin autoantibodies (IAAs). We measured autoantibodies reacting with GAD65 (GAD65AA), ICA512 (ICA512AA), and insulin in patients who recently had received a diagnosis of diabetes and in first-degree relatives prospectively identified and then followed because of the expression of high titers of ICA. Levels of IAAs (but not GAD65AA or ICA512AA) correlated inversely with age at diagnosis of diabetes and directly with time to diabetes onset among the ICA-positive relatives. In multiple linear regression models, the level of IAAs remained a significant predictor of the time to diabetes after allowing for first-phase insulin secretion. The unique and dramatic association of IAAs with progression to diabetes suggests that IAAs contribute directly to disease pathogenesis or that levels of IAAs are influenced uniquely by the process, leading--at different rates in different prediabetic individuals--to type I diabetes. In addition, the linear regression model described (involving two variables, first-phase insulin secretion and levels of IAAs) aids in the prediction of time to diabetes among ICA-positive relatives.

Adolescent↗
PubMed1977

Regulation of the growth and development of sympathetic neurons in vivo.

The superior cervical ganglion (SCG) in the neonatal mouse and rat has been employed as a model system to study the regulation of ontogeny of presynaptic cholinergic nerves and postsynaptic adrenergic neurons. During postnatal development presynaptic choline acetyltransferase (ChAc) activity increases 30- to 40-fold, whereas postsynaptic tyrosine hydroxylase (T-OH) activity rises 6- to 8-fold. Transection of the presynaptic cholinergic nerves innervating the SCG prevents the normal development of T-OH activity and the normal accumulation of T-OH enzyme molecules in each postsynaptic neuron. The trans-synaptic regulation of T-OH development is apparently mediated by acetylcholine and postsynaptic depolarization, since pharmacologic ganglionic blockade also prevents normal maturation. Ganglion decentralization also prevents the normal maturation of adrenergic nerve terminals, and the development of end-organ innervation by SCG. Consequently, trans-synaptic factors regulate the ontogeny of adrenergic terminals as well as perikarya. Moreover, normal efferent as well as afferent connections are apparently required for sympathetic development, since removal of salivary glands and orbital contents, target organs of the SCG, in neonates also prevents T-OH development in the ganglia. The postsynaptic neuron contributes to the development of presynaptic cholinergic fibers in SCG. Selective destruction of adrenergic neurons in neonatal mice with either 6-hydroxydopamine or antiserum to nerve growth factor prevents the normal maturation of ChAc activity in presynaptic terminals of SCG. Thus, presynaptic and postsynaptic cells appear to exert reciprocal regulatory influences during ontogeny.

Age Factors↗
PubMed1996

Dopamine-beta-hydroxylase and tyrosine hydroxylase immunoreactive neurons in the human brainstem.

Immunohistochemistry of dopamine-beta-hydroxylase in the human hind brain indicates that neuronal cell bodies containing the antigen form prominent populations in the nucleus tractus solitarius and nearby medial and dorsal edge of the medial vestibular nucleus. They are frequent in and around the periphery of the dorsal motor nucleus of the vagus and in an oblique band extending from that region to the ventrolateral aspect of the reticular formation, where they are most numerous at the mid medullary levels. Dopamine-beta-hydroxylase immunoreactive neurons are also closely packed in the nuclei coeruleus and subcoeruleus. Concomitant immunohistochemistry for tyrosine hydroxylase demonstrates small numbers of neuronal cell bodies that are reactive only for this antigen, and which do not contain detectable dopamine-beta-hydroxylase. Such neurons are present in the nucleus tractus solitarius, the pontine lateral parabrachial nucleus and within the core of the rostral pontine reticular formation. Some medullary and pontine axon bundles similarly stain for tyrosine hydroxylase but not for dopamine-beta-hydroxylase. These differential staining patterns suggest, among other possibilities, that in humans some neurons of the caudal brainstem are dopamine (if they contain the second step catecholamine synthesizing enzyme, aromatic L-aminoacid decarboxylase) rather than noradrenaline or adrenaline containing catecholamine neurotransmitters.

Aged↗
PubMed1980

Reduced brain monoamine synthesis by systemic treatment with terbutaline, a beta 2-receptor agonist.

The effects of acutely (5 mg/kg s.c.) or subchronically (2.5 mg/kg s.c., twice daily, 4 days) administered terbutaline, a beta 2-receptor agonist, on the in vivo rate of tryptophan and tyrosine hydroxylation in various rat brain parts were studied. The accumulation of 5-hydroxytryptophan (5-HTP) during 30 min following treatment with NSD 1015, 100 mg/kg i.p., an inhibitor of L-aromatic amino acid decarboxylase, appeared reduced in several brain parts by the terbutaline treatments, the effect being significant in the limbic forebrain and the hemispheres after subchronic administration. This treatment also reduced the simultaneously measured accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the same brain parts as well as in corpus striatum, where the effect was seen also after acutely administered terbutaline. The concentration of tryptophan in the various brain parts was not significantly affected by the terbutaline treatments and the tyrosine levels were only reduced in some brain parts (the hemispheres and the brain stem). The central effects obtained by terbutaline treatment may be mediated indirectly via peripheral inputs to e.g. the monoamine carrying neurons and/or via putative changes in cerebral blood flow.

5-Hydroxytryptophan↗
PubMed1994

The effect of short-photoperiod exposure on tuberoinfundibular dopamine neurons in male and female Syrian hamsters.

In male hamsters, exposure to a short photoperiod results in a significant decrease in median eminence (ME) dopamine (DA) concentrations. The mechanism responsible for this decrease in DA is unknown. The experiments described in this paper were designed to examine the effects of photoperiod on DA metabolism and synthesis in the ME to determine if a change in these processes is responsible for the short-photoperiod-induced decrease in ME DA concentrations. In the first experiment, the metabolism of DA in tuberoinfundibular dopamine (TIDA) neuronal terminals was determined by measuring ME concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC; a major metabolite of DA) and DA in male and female hamsters housed in long and short photoperiods. In both males and females, exposure to the short photoperiod induced a collapse of the reproductive system and a reduction in circulating prolactin. In males, but not in females, exposure to the short photoperiod reduced ME DA concentrations; however, DOPAC concentrations were not affected by photoperiod. Thus, the decrease in ME DA seen in males is not the result of an increase in DA metabolism. In the second experiment, tyrosine hydroxylase (TH) activity in the ME of males was determined by injecting animals housed in long and short photoperiods with a L-aromatic amino acid decarboxylase inhibitor (NSD 1015) and measuring 3,4-dihydroxyphenylalanine (DOPA). Consistent with Experiment 1, ME DA concentrations were significantly decreased in gonadally regressed males housed in a short photoperiod; however, ME DOPA accumulation was not affected. Thus, the observed decrease in DA is not the result of a decrease in TH activity in the ME. The results of the experiments presented here indicate that (1) in males but not females, the decrease in circulating prolactin seen in animals housed in a short photoperiod for 12 weeks is associated with a decrease in ME DA concentrations, and (2) the decrease in ME DA seen in males housed in a short photoperiod is not the result of an increase in DA metabolism or a decrease in synthesis by TIDA neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Differentiation of noradrenergic traits in the principal neurons and small intensely fluorescent cells of the parasympathetic sphenopalatine ganglion of the rat.

Catecholamine synthetic enzymes are found in many cranial parasympathetic principal neurons, and in the small intensely fluorescent (SIF) cells that populate parasympathetic as well as sympathetic ganglia. While there is evidence that the acquisition of noradrenergic properties in sympathetic neuron precursors depends on factors that these cells encounter in the trunk environment, the mechanisms that direct the development of noradrenergic traits in cranial parasympathetic neurons and SIF cells are not understood. The present study examines the time course of appearance of tyrosine hydroxylase (TH) immunoreactivity in the principal neurons and SIF cells of the rat sphenopalatine ganglion. We show that the sphenopalatine ganglion of normal adult rats contains both a small population of TH-immunoreactive principal neurons and many SIF cells. The TH-immunoreactive principal neurons do not synthesize or store detectable catecholamines, even though the majority of sphenopalatine ganglion neurons do contain 1-amino acid decarboxylase catalytic activity. Sphenopalatine ganglion principal neurons do not accumulate detectable levels of exogenous catecholamines. This observation suggests that they lack a high affinity norepinephrine uptake system. In contrast to what has been observed previously for sympathetic neurons, the appearance of TH immunoreactivity in sphenopalatine neurons is not temporally correlated with the cessation of neural crest cell migration. The first TH-immunoreactive neurons do not appear in the sphenopalatine ganglion until Embryonic Day 16.5, 2 days after the ganglion has condensed and process outgrowth has begun. The number of sphenopalatine neurons that express TH immunoreactivity increases dramatically between Embryonic Day 18.5 and Postnatal Day 1, but then decreases. In fact, the percentage of sphenopalatine neurons that express TH immunoreactivity is almost fivefold higher in newborn than in adult rats. SIF cells cannot be definitively identified in the sphenopalatine ganglion until after Embryonic Day 18.5. The time course of appearance of TH immunoreactivity in sphenopalatine ganglion cells raises the possibility that TH expression is stimulated in these cells by factors encountered either at their condensation site or at their target, such as glucocorticoids or nerve growth factor. The relatively late appearance of SIF cells in the sphenopalatine ganglion argues against the hypothesis that SIF cells are the precursors of all autonomic neurons.

Animals↗
PubMed1991

Tottering and leaner mutations perturb transient developmental expression of tyrosine hydroxylase in embryologically distinct Purkinje cells.

The mouse mutants tottering and leaner exhibit neurologic disorders associated, in part, with global noradrenergic hyperinnervation. Therefore, the expression of tyrosine hydroxylase (TH) mRNA and protein was examined in mutant and control mice. TH expression was normal in the major catecholaminergic nuclei. However, TH was expressed in vermal Purkinje cells of adult mutant but not control mice. TH expression in the Purkinje cells of both mutants was first observed on P21 and persisted throughout adulthood; in contrast, Purkinje cells of normal mice expressed TH transiently during development from P21 to P35. Thus, tottering and leaner mice are deficient in suppressing the normal transient expression of TH in developing Purkinje cells, suggesting that the protein encoded by the tg locus may play a crucial role in neuronal development.

Animals↗
PubMed1976

Ontogenetic development of locomotor activity and rate of tyrosine hydroxylation.

A combined biochemical and behavioral study was performed postnatally on albino rats. An almost linear increase in total motor activity was observed from 1 to 15 days of age followed by a pronounced decrease in motor activity between days 15 and 18. The in vivo rate of tyrosine hydroxylase activity in whole brain was estimated by means of measuring accumulation of L-3,4-dihydroxyphenylalanine (Dopa) after administration of an inhibitor of aromatic amino acid decarboxylase NSD 1015. Additionally, Dopa accumulation was studied in regional brain areas in 10 and 14-day-old animals. A slight gradual increase in the amount of Dopa accumulation in whole brain was observed from 1 to 10 days of age, followed by a pronounced increase between 10 and 14 days. Regional studies revealed that the increase in Dopa accumulation was primarily located to striatum. The data suggest an involvement of central catecholamine neurons possibly dopaminergic, terminating in striatum. The decrease in motor activity observed after 15 days of age is interpreted as involvement of maturing inhibitory pathways of noncatecholaminergic origin.

Animals↗
PubMed1996

Effect of a pyridinium metabolite derived from haloperidol on the activities of striatal tyrosine hydroxylase in freely moving rats.

The effects of a pyridinium metabolite (HPP+) derived from haloperidol (HP) on in vivo tyrosine hydroxylation was evaluated in freely moving rats. As an index of the in vivo activity of tyrosine hydroxylase (TH), the rat striatum was perfused with NSD-1015, and extracellular 3,4-dihydroxyphenylalanine (DOPA) levels were measured. HPP+ (1 mM) gradually reduced tyrosine hydroxylation to 30% of the basal level, although the effect was less potent than 1-methyl-4-phenylpyridinium ion (MPP+). On the contrary, HPP+ at a 0.1 mM dose decreased in 5-hydroxyindoleacetic acid (5-HIAA) level, but did not affect dopamine metabolites. The present study revealed that HPP+ irreversible inhibited in vivo tyrosine hydroxylation by the same manner of MPP+. However, the neurotoxic effects of HPP+ in vivo would be selective for serotonergic over dopaminergic neurons, which distinguishes the toxic profile of this compound compared to that of MPP+.

1-Methyl-4-phenylpyridinium↗
PubMedDate not supplied

No effect of age and estrogen on aromatic L- amino acid decarboxylase activity in rhesus monkey brain.

A variety of studies have shown an effect of estrogen on dopamine function and suggest that estrogen may modulate central dopaminergic activity. Positron emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex and striatum in six aged, but pre-menopausal, female monkeys before and after ovariectomy (OVX). Dynamic PET brain uptake data and metabolite-corrected blood input functions were fit to a three-compartment model for FMT uptake. Prior to OVX, all animals showed preferential accumulation of the tracer bilaterally in the striatum and less but measurable activity in the frontal cortex. Paired comparisons showed that there were no significant differences in FMT uptake (K(i)) in either brain region before and after OVX. In addition, FMT uptake did not differ from a group of young adult female monkeys at either time point. These findings may represent a compensatory up-regulation of aromatic L- amino acid decarboxylase (AADC) activity.

Age Factors↗
PubMed2000

Autoimmune markers in young Malaysian patients with type 1 diabetes mellitus.

This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage.

Adolescent↗
PubMed1993

Regulation of hypothalamic preprogrowth hormone-releasing factor messenger ribonucleic acid expression in food-deprived rats: a role for histaminergic neurotransmission.

To determine the component(s) of dietary protein that regulates GH-releasing factor (GRF) synthesis, we measured hypothalamic prepro-GRF mRNA by solution hybridization/nuclease protection analysis in food-deprived rats refed protein-free diets (PF) supplemented with individual amino acids. Adult male Sprague-Dawley rats were allowed free access to food (Fed), food deprived for 72 h (FD), or FD then refed for 72 h with a normal (NF) diet, a protein-free (PF) diet, or PF diets containing tyrosine, tryptophan (Trp), glutamic acid, or histidine (His). Food-deprived rats displayed the expected 80% reduction in hypothalamic prepro-GRF mRNA. Upon refeeding, levels were normalized in rats refed a normal diet, but not in those refed a PF diet alone or with tyrosine, Trp, or glutamic acid. In contrast, prepro-GRF mRNA was restored to 70% of Fed values by a PF diet with His. Supplementing a PF diet with His was sufficient to maintain hypothalamic prepro-GRF mRNA expression, as 3 days of feeding replete rats with PF diet or PF diet with added Trp resulted in a 50% reduction in prepro-GRF mRNA, whereas levels were reduced 25% by feeding animals a PF diet with His. Groups of rats allowed free access to food were treated for 72 h with two daily injections of 100 mg/kg alpha-fluoremethylhistidine, a specific irreversible inhibitor of histidine decarboxylase, to determine if the effect of His on prepro-GRF mRNA depended on neural conversion to histamine. alpha-Fluoremethylhistidine-treated rats showed a 40% reduction in hypothalamic prepro-GRF mRNA, with no concomitant change in preproneuropeptide-Y or preprosomatostatin. These data indicate that decreased hypothalamic prepro-GRF mRNA in FD rats is due in part to the lack of dietary and provide clear evidence for a role of the histaminergic neural system in the regulation of hypothalamic GRF expression.

Animals↗
PubMed1982

Studies on the regulatory mechanism of the tyrosine hydroxylase system in adrenal slices by using high-performance liquid chromatography with electrochemical detection.

A new method was developed to study the tyrosine hydroxylase (TH) system in rat adrenal slices by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). TH activity was measured by determining DOPA, formed in adrenal slices containing all of the components of the TH system in the presence of an inhibitor of aromatic L-amino acid decarboxylase (NSD-1055), using a new and highly sensitive HPLC-ED method. The properties of the TH system in the slices were also examined. High K+ (52 mM) stimulated the formation of DOPA in the slices; this stimulation was not observed in Ca2+-free medium. Furthermore, the addition of ethyleneglycol bis (beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) to a Ca2+-free medium not only abolished the stimulation by high K+ but also significantly inhibited the conversion of L-tyrosine to DOPA. This suggests that intracellular Ca2+ may regulate TH activity in the adrenal medulla. The enzyme in homogenates of normal adrenal slices had two different Km values for the tetrahydropterin cofactor. Alteration of enzyme kinetics using homogenates of adrenal slices that had been treated in various ways suggests that changes in the proportions of the two forms of TH produced by intracellular Ca2+ may regulate the activity of this enzyme in the adrenal medulla.

Adrenal Glands↗
PubMed1991

Gamma-aminobutyric acid (GABAB) receptor-mediated inhibition of tyrosine hydroxylase activity in the striatum of rat.

The effects of GABA and GABA agonists on calcium and depolarization-dependent stimulation of tyrosine hydroxylase activity in striatal slices were studied. gamma-Aminobutyric acid and (-)baclofen inhibited, while muscimol and (+)baclofen did not affect, the stimulation of tyrosine hydroxylase. The inhibitory effect of GABA and (-)baclofen was blocked by the GABAB antagonist, phaclofen but not by the GABAA antagonist, picrotoxin. The data suggest that the activity of tyrosine hydroxylase on dopaminergic nigrostriatal terminals may be modulated by GABA via GABAB receptors.

Animals↗
PubMed1983

Effect of protein quality on dietary induction of hepatic ornithine decarboxylase.

Dietary induction of ornithine decarboxylase (ODC) in rat liver depended on the quality of protein in the diet. Zein did not induce ODC unless it was supplemented with the deficient amino acids, tryptophan and lysine. Similar phenomena were observed with gelatin (tryptophan and methionine) and hemoglobin (isoleucine). However, ODC was found to be significantly induced by an amino acid mixture simulating zein. The difference between amino acid diet and protein diet effects could not be explained by digestibility of zein. Unphysiologically rapid influx of amino acids appeared to induce ODC by a mechanism different from that by which dietary protein induced ODC. After ingestion of zein, the concentration of tryptophan and lysine decreased markedly in plasma and liver. However, it was confirmed that their supply from intracellular protein degradation continued even after feeding. In contrast to ODC, tyrosine aminotransferase was induced by zein as well as by casein, indicating that the requirement of tryptophan and lysine as precursor amino acids for enzyme synthesis was satisfied by reutilization of the amino acids liberated by intracellular protein degradation. Therefore, it was concluded that good quality protein was required for ODC induction mainly as a signal but not as a source of precursor amino acids.

Amino Acids↗
PubMed1996

Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.

1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions impaired by microsphere embolism. The mechanisms underlying this effect may be attributed to preservation of the ability to synthesize monoamines when the brain is ischaemic or oligaemic.

3,4-Dihydroxyphenylacetic Acid↗