Reduced Tyrosine Hydroxylase Activity Research Articles

Development of olfactory marker protein and tyrosine hydroxylase immunoreactivity in the transplanted rat olfactory bulb

Evidence suggests that tyrosine hydroxylase (TH) expression by juxtaglomerular (JG) neurons of the olfactory bulb (OB) is dependent upon input from primary olfactory neurons (ONs), which are identifiable using immunocytochemical localization (ICC-L) methods for olfactory marker protein (OMP). When the input from the continuously regenerating ONs is temporarily removed (either surgically or chemically), JG cells cease TH production until ON contact is reestablished. We are studying this transneuronal regulation using the rat OB in a transplantation (TX) model. Fetal OBs, labeled in utero with tritiated thymidine, were transplanted (TX) into a site vacated by removal of a neonatal host OB. Host animals were sacrificed at varying periods after TX. Alternate sets of frozen sections were then processed for autoradiography or using ICC-L for TH and OMP. As early as 1 week post-TX, OMP-positive fibers and glomerulus-like structures were seen throughout the TX OB. Despite this extensive and rapid OMP reinnervation, TH expression returned very slowly and the number of TH expressing cells never approached control levels. The reduced TH activity in TXs may be due to failure of JG cells to survive or to develop the correct phenotype under TX conditions. Alternatively, input from ON fibers may only be necessary, but not sufficient, for the expression of TH.

Mechanisms of Tyrosine Hydroxylase Regulation during Pregnancy: Evidence for Protein Dephosphorylation during the Prolactin Surges*

This study examined tyrosine hydroxylase (TH) activity in the stalk-median eminence (SME) and TH messenger RNA (mRNA) signal levels in the arcuate nuclei of the hypothalamus during early, middle, and late pregnancy and related these to circulating levels of ovarian steroids. In addition, this study evaluated the intracellular mechanism(s) which contributes to the semicircadian rhythm in tuberoinfundibular dopaminergic neuronal activity during early pregnancy. The catalytic activity of TH in the SME was determined from the in vitro rate of 3,4,dihydroxyphenylalanine accumulation after inhibiting DOPA decarboxylase with brocresine. TH mRNA signal levels were evaluated by in situ hybridization. TH mRNA signal levels in the arcuate nuclei were 30% lower at 1000 h on day 20 of pregnancy as compared to days 7 and 11, whereas TH activity in the SME at 1000 h was not significantly different on days 7, 11, 16, and 20. Serum PRL levels were low (3-6 ng/ml) and unchanged at 1000 h on days 7, 11, 16, and 20. Circulating progesterone levels increased from 111 to 191 ng/ml on days 7 and 16, respectively, and then declined to 69 ng/ml by day 20. Serum estradiol levels increased from 38 to 106 pg/ml on day 7 and 16, respectively, and then remained elevated on day 20. Thus, the reduction in TH mRNA signal levels during late pregnancy is temporally related to the increased estradiol/progesterone ratio. Elevated serum PRL levels at 0330 h and 1800 h on day 7 were characteristic of the nocturnal and diurnal PRL surges of early pregnancy. Circulating PRL levels were low during the intersurge times (2330 and 1000 h) on day 7 and at all times examined on day 11. TH activity in the SME on day 7 was lower during the PRL surges as compared to the intersurge times, whereas TH activity on day 11 was similar at all times and comparable to the intersurge levels of early pregnancy. Okadaic acid, a protein phosphatase inhibitor, reversed the reduction in TH activity during the nocturnal and diurnal PRL surges, but did not significantly alter TH activity during the intersurge period on day 7. TH mRNA signal levels in the arcuate nuclei were similar throughout day 7. These data indicate that protein dephosphorylation, but not changes in the TH gene expression, may contribute to the semicircadian rhythm in TH activity during early pregnancy.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in prenatal stage on the dopamine system in the postnatal mouse brain

A dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride (MPTP), administered to a pregnant female was found to affect postnatally the catecholamine metabolism of the pups. MPTP (5 mg/kg body weight/day) was administered to pregnant C57 Black BYA mice daily for 7 days between the 12th and 18th day of gestation. Dopamine levels and tyrosine hydroxylase (TH) activity were measured in the whole brain from the pups sacrificed after birth. In MPTP-treated pups at 7 days of age, TH total activity (TH activity/brain) did not change (92% of the control value), while TH specific activity (TH activity/mg protein) was increased to 163% of that in control mice. Thus, TH homospecific activity (TH activity/mg TH protein) doubled compared to the control mice. At 28 days of age, both the total activity and the specific activity of TH in the brains of postnatal mice were reduced to 50% and 78% of the control, respectively. Dopamine concentration in the striatum was also reduced significantly. Reduction in the TH activity and dopamine concentration were also observed at the age of 12 weeks. These data suggest that the prenatal exposure to MPTP induced a prolonged reduction of TH activity in the brains of mice with a transient increase of TH homospecific activity during the postnatal period.

Toxicity of 1‐Methyl‐4‐Phenylpyridinium for Rat Dopaminergic Neurons in Culture: Selectivity and Irreversibility

Cultures of dissociated embryonic rat mesencephalic cells were exposed to 10 microM 1-methyl-4-phenylpyridinium (MPP+), a concentration shown earlier to result in loss of greater than 85% of tyrosine hydroxylase (TH)-positive neurons without affecting the total number of cells observed by phase-contrast microscopy. To characterize better the selectivity of the toxic action of MPP+, other parameters were measured reflecting survival and function of dopaminergic or nondopaminergic neurons. Exposure of cultures to 10 microM MPP+ for 48 h reduced TH activity to 11% of control values without reducing protein levels. [3H]Dopamine uptake was reduced to less than 4% of control values, whereas the uptake of gamma-[3H]aminobutyric acid ([3H]GABA) was not affected in these cultures. This same treatment failed to reduce the number of cholinergic cells visualized in septal cultures and did not affect either choline acetyltransferase activity or high-affinity choline uptake. To assess for possible recovery of dopaminergic neurons, cultures were exposed to 10, 1.0, or 0.1 microM MPP+ for 48 h and then kept for up to 6 days in MPP(+)-free medium. After exposure to 10 microM MPP+, the number of TH-positive neurons, their neurite density, TH activity, and [3H]dopamine uptake remained at constant, reduced levels throughout the period of observation after termination of exposure, whereas GABA uptake remained normal. Treatment with lower concentrations of MPP+, i.e., 1.0 and 0.1 microM, induced less pronounced dopaminergic toxic effects. However, no recovery was seen after posttreatment incubation in toxin-free medium. These findings provide evidence that MPP+ treatment results in highly selective and irreversible toxicity for cultured dopaminergic neurons.

Region‐specific consequences of PCD gene expression in the olfactory system

These studies investigated the response of olfactory bulb juxtaglomerular dopamine neurons to the loss of mitral cells in 6-7-month-old Purkinje cell degeneration (PCD) mice. Previous studies in normal mice, with tyrosine hydroxylase (TH) enzyme as a marker, demonstrated that following peripheral olfactory afferent denervation the juxtaglomerular dopamine neurons exhibited a large reduction in TH activity and immunoreactivity. These intrinsic dopamine neurons also receive afferent input via dendrodendritic contacts with mitral cells. In contrast to the deficits produced by peripheral denervation, following mitral cell degeneration in homozygous recessive PCD mice, TH activity and immunoreactivity were unaltered as compared to normal heterozygous littermates. Moreover, TH activity in the substantia nigra also was unchanged, thus suggesting that the dopamine phenotype is resistant to the influences of the pcd gene. Despite the absence of a well-defined effect of the pcd gene on neurons bearing the TH phenotype, the expression of this mutation within the olfactory system is not limited to mitral cell degeneration. The current studies also demonstrate the absence of the anterior commissure, especially pars anterior, in homozygous recessive PCD mice at 6-7 months postnatal. Whether or not the loss of the anterior commissure is a primary effect or one that is secondary to mitral cell degeneration, this structural alteration provides evidence that the pcd gene exerts more widespread effects within the olfactory system that previously appreciated. The neuronal specificity of those effects remains apparent as indicated by the lack of change in TH expression.

Sex-Related Alterations in Hypothalamic Tyrosine Hydroxylase after Neonatal Monosodium Glutamate Treatment

This study compared tyrosine hydroxylase (TH) mRNA signal levels, relative quantity of TH protein, and the catalytic activity of TH in the tuberoinfundibular dopaminergic neurons (TIDA) of male and ovariectomized (OVEX) female rats. In addition, the effects of monosodium glutamate (MSG) neurotoxicity on these parameters of TH regulation were evaluated. Neonatal rats were injected with MSG (4 mg/g body weight) or 10% sodium chloride (controls) on alternate days for the first 10 days of life. Females were ovariectomized on day 45 of age, and all rats were used between 60 and 80 days of age. The TH mRNA signal levels, as assessed by an in situ hybridization technique, were 2-fold higher in control females than in control males, whereas the number of TH mRNA-containing cells was similar between sexes. The TH immunostainings of the TIDA perikarya in the arcuate nucleus and of the nerve terminals in the median eminence were qualitatively more intense in females than males. The catalytic activity of TH, as determined by in vitro DOPA accumulation in the stalk-median eminence, was 3-fold greater in females than males. Neonatal MSG-treatment resulted in a marked reduction in the number of TH mRNA-containing cells and TH-immunopositive cells in the arcuate nucleus of both sexes, as well as a decrease in the intensity of TH immunostaining in the median eminence. The cellular mRNA signal levels for TH were markedly reduced in females after MSG treatment, but were unchanged in males. MSG treatment reduced TH activity to 20% of control levels in females, but did not alter enzyme activity in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A, an immune suppressor, enhanced neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was systemically administrated into C57BL/6N mice for 8 days. Tyrosine hydroxylase activity and dopamine content in striatum and hypothalamus were reduced markedly, and the reduction was more manifest in the striatum. Cyclosporin A, an immune suppresser, enhanced the neurotoxicity of MPTP, when it was injected to mice in combination with MPTP. Tyrosine hydroxylase activity in the striatum was reduced to 109 ± 20 from 350 ± 46 pmol/min/mg protein of control, when mice were injected by MPTP alone. The enzyme activity was further reduced to 68.4 ± 12.2 pmol/min/mg protein by injection of MPTP in combination to cyclosporin A. In addition, dopamine and biopterin contents in the striatum decreased quite in parallel to the reduction of tyrosine hydroxylase activity. On the other hand, cyclosporin A itself did not effect tyrosine hydroxylase activity and dopamine and biopterin contents in the striatum and hypothalamus. These data suggest cumulative effect of cyclosporin A to the neurotoxicity of MPTP.

Reproductive hormones control striatal tyrosine hydroxylase activity in the male rat

The effects of castration, hypophysectomy and testosterone treatment on striatal tyrosine hydroxylase (TOH) activity were examined in male rats. Enzyme activity was measured by means of high-performance liquid chromatography (HPLC) determination of l-3,4-dihydroxphenylalanine (DOPA) formed. Serum levels of both testosterone and luteinizing hormone (LH) were measured by radioimmunoassay (RIA). Castration, but not hypophysectomy, reduced TOH activity in the striatum. The administration of testosterone propionate (TP) to castrated animals in a dose of 10 μg/100 g b.wt. during the two days previous to sacrifice, completely prevented the castration-induced reduction of striatal TOH activity. In orchidectomized rats treated with different doses of testosterone propionate (TP) up to 20 μg/100 g b.wt., the levels of striatal TOH activity were apparently related to either the dose-related increase of serum testosterone or the decrease of serum LH. Higher doses of the androgen failed to further modify striatal TOH activity, in spite of the dose-related elevation of serum testosterone concentration. These results suggest that circulating levels of gonadal and/or pituitary hormones partially control dopaminergic synthesis in striatal terminals, which in turn may account for some behavioral effects of reproductive hormones.

Effect of 1-methyl-4-phenylpyridinium ion (MPP +) on catecholamine levels and activity of related enzymes in clonal rat pheochromocytoma PC12h cells

1-Methyl-4-phenylpyridinium ion (MPP +), a metabolite of a neurotoxin, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, was found to reduce dopamine (DA) level and the activity of enzymes related to its metabolism in clonal rat pheochromocytoma PC12h cells. After 6 days' culture in the presence of 1 mM and 100 μM MPP +, DA content in PC12h cells was reduced markedly, but with MPP + at concentrations lower than 10 μM, DA levels in the cells did not change. The amounts of 3, 4-dihydrophenylacetic acid (DOPAC), a metabolite of DA were reduced markedly in culture medium and in PC12h cells cultured with MPP + at concentrations higher than 1 μM. MPP + was found to reduce the enzyme activity of tyrosine hydroxylase (TH), monoamine oxidase (MAO) and aromatic L-aminoacid decarboxylase (AADC). In the presence of MPP + at concentrations higher than 10 μM, reduction of TH activity in the cells was more pronounced than reduction of cell protein or of the activity of a non-specific enzyme, β-galactosidase. With 1 mM and 100 μM MPP +, MAO activity was reduced to about 30% of that in control cells. Reduction was observed with MPP + at concentrations higher than 1 μM. AADC was the most sensitive to MPP + and its activity was reduced markedly in the cells cultured with 100 nM MPP +. These results indicate that MPP + inhibits not only the biosynthesis of catecholamines, but also the enzyme participating in their catabolism in cells, and may thus perturb catecholamine levels in the brain.

Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content

We examined both in vitro tyrosine hydroxylase (TH) activity and TH content determined by a new enzyme immunoassay in the mouse striatum after repeated systemic injection of MPTP. Repeated systemic administration of MPTP to mice (30 mg/kg per day, subcutaneously for 8 days) caused an approximately 65% decrease of both TH activity and TH content in the striatum. The intensity of immunohistochemical staining of TH protein in the striatum was also reduced in MPTP-treated mice. These results indicate that the reduction of TH activity in vitro after the repeated administration of MPTP is due to reduction of TH protein as a result of nerve degeneration.

Effect of starvation on hypothalamic tyrosine hydroxylase activity in adult male rats

The activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis, was determined in the mediobasal hypothalamus of adult male rats during acute and semistarvation. 3,4-Dihydroxyphenylalanine (DOPA) formed by TH was measured using high-performance liquid chromatography (HPLC). Acute starvation, as well as 3 weeks of semistarvation on a high-protein low-carbohydrate diet (CST PR) reduced TH activity significantly. Three weeks of a low-protein high-carbohydrate diet (CST KH) did not affect TH activity. While maximal velocity ( V max) is significantly diminished in acute starvation and in semistarvation with a high-protein low-carbohydrate diet, K d-values for tyrosine were not changed. These results that TH activity in the brain contributes to decreased norepinephrine (NE) turnover in starvation.

Differential effects of transection of the spinal cord and splanchnic nerve on adrenal tyrosine hydroxylase and catecholamines

The role of spinal pathways in the regulation of adrenal medullary tyrosine hydroxylase and catecholamines was studied in adult rats subjected to spinal cord transection at the third thoracic level. In these animals the sympathoadrenal preganglionic neurons were isolated from their supraspinal afferents. This treatment led after three days to a progressive reduction of tyrosine hydroxylase activity and dopamine content (as compared to unoperated controls) until at least the 10th day. The results of the administration of dexamethasone or adrenocorticotropic hormone to spinalized rats suggest that in these animals glucocorticoid hypersecretion is not involved in the decline of adrenal tyrosine hydroxylase and that in fact adrenocorticotropic hormone supplementation can prevent it. A neurogenic origin for the depression of adrenomedullary function is favoured because unilateral splanchnicotomy (which by itself does not affect adrenal tyrosine hydroxylase), prior to cord section, prevented the diminution of tyrosine hydroxylase activity in the denervated gland. The decline of adrenal tyrosine hydroxylase and dopamine after spinal section may result from a decrease of modulatory impulses to the adrenal from decentralized sympathoadrenal preganglionic neurons in the isolated cord, following the loss of a descending facilitation of these neurons and/or the release of a segmental interneuronal inhibition of these neurons from a descending inhibitory influence. Such descending pathways may decussate partially below the low cervical level because rats with hemisection of the cord at C 6-C 7 exhibited no decline of adrenal tyrosine hydroxylase or of dopamine measured on either side seven days postoperatively.

Neurochemical and Histochemical Characterization of Neurotoxic Effects of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine on Brain Catecholamine Neurones in the Mouse

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemically. The depleting effects were more pronounced after repeated MPTP administration and the most marked reductions were observed after 2 X 50 mg MPTP/kg s.c., when DA in striatum and NA in frontal cortex were reduced by greater than 90% 1 week after MPTP. Mice with such catecholamine depletions were markedly sedated and almost completely immobilized. The behavioural syndrome after MPTP resembled that seen after reserpine, a monoamine-depleting drug. MPTP also caused a long-lasting reduction of catecholamine uptake in striatal DA and cortical NA nerve terminals and reduced tyrosine hydroxylase activity in these regions. There was no evidence that MPTP caused any marked DA and NA cell body death. MPTP given acutely transiently elevated serotonin levels. The results are compatible with a neurotoxic action of MPTP on both DA and NA nerve terminals. The nigro-striatal DA and the locus coeruleus NA neurone systems appeared to be most susceptible. Synthesis and utilization of residual striatal DA and cortical NA were increased, as often observed in partially denervated monoamine-innervated brain regions. Both DA and NA showed a gradual recovery, which took months to become complete and may have been related to a regrowth of catecholamine nerve terminals.

Dopaminergic neurons in the mediobasal hypothalamus of old rats: Evidence for decreased affinity of tyrosine hydroxylase for substrate and cofactor

The effect of aging on the activity of tyrosine hydroxylase (TH) and on the number of TH-positive perikarya in the hypothalamus was studied in old and young female rats. The activity of TH in the mediobasal hypothalamus (MBH) of old rats was significantly ( P < 0.025) less than that in young rats. In old rats, the K m of TH for tyrosine as well as cofactor, 6-methyl-5,6,7,8-tetrahydropterine (6MPH 4), was markedly greater than the K m in young rats. The maximal velocity was only slightly reduced in old animals. Contiguous coronal sections of the brain of an old and a young female rat were immunocytochemically stained for TH, and the TH-positive perikarya in the hypothalamus were counted. In the circumventricular region, 6793 TH-positive perikarya were present in the young brain and 6632 in the old brain. In the arcuate region, 2868 and 2760 TH-positive perikarya were counted in the young and old brain, respectively. It is concluded that the reduced TH activity in the MBH of old rats is not a consequence of a reduction in the number of TH-positive perikarya in the arcuate or circumventricular regions of the hypothalamus but is due to a reduction in the affinity of TH for its substrate and cofactor.

Reduced tyrosine hydroxylase activity in nigrostriatal system of sinoaortic-denervated rats

Tyrosine hydroxylase activity was measured in the caudate nucleus and substantia nigra (pars compacta) of sinoaortic-denervated (SAD) and sham-operated (SO) rats 3 days after operation. The SAD groups had approximately a 50%, statistically significant, reduction of enzyme activity in both regions and also a significant reduction of dopamine in caudate nucleus. These results suggest a probable link between cortico-somatomotor integration and neural input from arterial baroreceptor neural pathways.

Selective sympathetic neural changes in hypertrophied right ventricle.

Selective pressure overload of the right ventricle in guinea pigs resulted in early and sustained reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the right ventricle. No changes in tyrosine hydroxylase activity were detected in stellate ganglia sinoatrial (SA) nodal region, atrioventricular (AV) nodal region, or left ventricle. Reductions in tyrosine hydroxylase activity in stressed right ventricle were similar regardless of duration of pulmonary artery constriction, extent of hypertrophy, presence or absence of hepatic congestion, and preservation or depletion of catecholamines. The changes may represent localized loss of sympathetic nerve fibers; factors involved directly in the process of pressure-overload-induced hypertrophy may be responsible. However, sympathetic nerves remaining in hypertrophied ventricle respond normally to cold-induced sympathetic activation. The reduction in tyrosine hydroxylase activity and the maintenance of norepinephrine turnover in residual innervation to hypertrophied right ventricle support the concept that sympathetic neural regulation of hypertrophied cardiac tissue is altered but not lost.

Immunosuppressive agents prevent guanethidine-induced destruction of rat sympathetic neurons

Chronic administration of guanethidine to rats causes destruction of peripheral sympathetic neurons. Neuronal destruction, characterized morphologically by small cell infiltration and the reduction in the number of neurons within sympathetic ganglia, and biochemically by a marked reduction in tyrosine hydroxylase activity, occured reproducibly by day 7 of treatment following 5 daily injections of 50 mg/kg guanethidine sulfate. Several observations in the literature suggested that guanethidine-induced destruction may occur by an immunologically mediated mechanism. Experiments were therefore designed to test the effects of immunosuppressive agents on guanethidine sympathectomy. A single exposure to either γ-irradiation or cyclophosphamide, administered 8 h prior to the initiation of guanethidine treatment, protected against guanethidine-induced destruction in a dose-related manner and was virtually complete with either 900 rads of irradiation or with 100 or 150 mg/kg of cyclophosphamide. Cyclophosphamide afforded complete protection only if administered immediately prior to guanethidine treatment suggesting that it was acting during the proliferative phase of an immune response rather than non-specifically. Pretreatment with either irradiation or cyclophosphamide had no effect on the sympathectomy produced by treatment with either 6-hydroxydopamine or antibodies to nerve growth factor, nor did it prevent the accumulation of guanethidine within the sympathetic ganglia. Concurrent treatment with either azathioprine or dexamethazone also provided partial protection against guanethidine sympathectomy. These results strongly suggest that the destruction of sympathetic neurons induced by guanethidine occurs by an immunologically mediated mechanism.

Biochemical evidence for alteration of neostriatal dopaminergic function by 5,7-dihydroxytryptamine.

Unilateral injection of 5,7-dihydroxytryptamine (DHT) into the rat neostriatum markedly reduced not only striatal tryptophan hydroxylase (TPH) activity but also striatal tyrosine hydroxylase (TH) activity and dopamine (DA) concentration measured 10--15 days later. The decrease in striatal TH activity was dose related over the range of 8--32 micrograms of DHT; a dose of 16 micrograms reduced striatal TH activity to 40--50% of control, DA concentration to 38% of control, and TPH activity to 5--20% of control. Intrastriatal injection of 16 micrograms of DHT reduced TH activity in the ipsilateral substantia nigra to 51% of control. Pretreatment with amfonelic acid, a potent DA uptake inhibitor, significantly reduced the effect of DHT on striatal and nigral TH activity and striatal DA concentration without affecting the DHT-induced decrease in striatal TPH activity. Desmethylimipramine (5 and 25 mg/kg) had no effect on the DHT-induced decrease in striatal TH activity. Striatal choline acetyltransferase and glutamic acid decarboxylase activities were not decreased by 16 micrograms of DHT. The results indicate that DHT can alter dopaminergic function in the rat neostriatum through a direct effect of the drug on DA neurons.

Effects of antibodies against nerve growth factor on the postnatal development of substance P-containing sensory neurons

Administration of anti-nerve growth factor (NGF)-antibodies to newborn rats produces a marked but reversible reduction of the substance P content in dorsal root ganglia. This is in contrast to the effect of anti-NGF-antibodies on sympathetic ganglia, where they cause a destruction of the adrenergic neurons as is evident in the irreversible reduction of tyrosine hydroxylase activity.

Tyrosine hydroxylase activity in the superior cervical ganglion during herpes simplex virus infection: Correlation with viral titers and viral antigen

The activity of tyrosine hydroxylase (TH) was measured in the superior cervical ganglion (SCG) of the mouse during herpes simplex virus (HSV) infection. TH activity remained at control levels or actually increased during acute infection at a time when viral titers of SCG homogenates were at their peak and viral antigen was detected in from one-third to one-half of ganglionic neurons. A rapid decline in TH activity followed and coincided with falling viral titers, disappearance of viral antigen and replacement of neurons by inflammatory cells. Immunization partially prevented this reduction of TH activity. In addition, when mice were immunosuppressed by cyclophosphamide, TH activity was relatively preserved early in the course of infection despite high viral titers in the ganglion and the presence of viral antigen and histopathological alterations in nearly 100% of neurons. These results suggest that a cellular ‘luxury function’, in this case TH activity, can be preserved and perhaps even augmented during neuronal HSV infection. Indeed, activity of this enzyme may persist until late into the acute phase of infection, perhaps up to the point of cell death induced either by immune-mediated or direct virus-induced cell lysis.