Anatomy of the cutaneous surface of the male genitalia, with elaboration upon the inner preputial coronal-shaft junction.

INTRODUCTION: Descriptions of the penile prepuce in anatomical and clinical texts either omit details or contain a small, yet potentially serious, error with regard to the manner of its attachment to the penis. OBJECTIVE: This study sought to cast light on a ubiquitous but poorly understood and under-appreciated structure, while correcting a long-standing mistake in the medical literature. STUDY DESIGN: The foreskins of five male stillborn babies were dissected and carefully examined. Tissue from the apposing surfaces of the various regions of the inner and outer prepuce surfaces and the transition zone itself were collected, embedded in paraffin, sectioned, stained, examined and photographed under microscopy. RESULTS: Contradicting the prevailing descriptions in the literature that the inner prepuce is a single, uniform sheath, this study's observations and histological findings demonstrated that it actually splits into separate laminae that connect distally to the shaft at the base of the corona and proximally with the shaft fascia, respectively (Figure). DISCUSSION: The penile prepuce is a discrete and deceptively complex part of the male anatomy, yet key details of its interposing surfaces are inaccurately described or entirely omitted in the literature. Understanding the normal anatomy of the prepuce is critically relevant, particularly for urologists and others involved in the performance of circumcision. For example, avoiding potentially catastrophic avulsion of the inner preputial remnant beyond the coronal sulcus during circumcision and accurate assessment of tissue positioning prior to penile reconstruction in cases of hypospadias. CONCLUSION: The findings of this study correct a misunderstanding in the anatomy of the prepuce.

Neurobehavioral damage to cholinergic systems caused by prenatal exposure to heroin or phenobarbital: cellular mechanisms and the reversal of deficits by neural grafts.

Despite the basic differences in their underlying biological targets, prenatal exposure to heroin or phenobarbital produces similar syndromes of neurobehavioral deficits, involving defects in septohippocampal cholinergic innervation-related behaviors. At the cellular level, these deficits are associated with cholinergic hyperactivity, characterized by increased concentrations of muscarinic receptors and enhanced second messenger activity linked to the receptors. In the present study, we determined whether the cellular changes are mechanistically linked to altered behavior, using two different approaches: neural grafting and correlations between behavior and biochemistry within the same individual animals. Mice were exposed transplacentally to phenobarbital or heroin on gestation days 9-18 and, as adults, received fetal cholinergic grafts or were sham-operated. Prenatal drug exposure resulted in deficits in behavioral performance tested in the eight-arm radial maze, accompanied by increases in hippocampal M(1)-muscarinic receptor expression and muscarinic receptor-mediated IP formation. Neural grafting reversed both the behavioral deficits and the muscarinic hyperactivity. In the drug-exposed offspring, there was a significant correlation between maze performance and carbachol-induced inositol phosphate (IP) formation. These studies indicate that deficits of cholinergic function underlie the neurobehavioral deficits seen in the hippocampus of animals exposed prenatally to heroin or phenobarbital, and consequently that the observed cholinergic hyperactivity is an unsuccessful attempt to compensate for the loss of cholinergic function. The fact that the damage can be reversed by neural grafting opens up novel approaches to the restoration of brain function after prenatal insults.

Protein synthesis inhibition in neocortical grafts evaluated by systemic amino acid uptake autoradiography.

The temporal pattern of protein synthesis inhibition was examined in grafted neocortical neurons using [(3)H]valine in vivo autoradiography. Neuronal uptake levels of systemically administered (3)H-labeled amino acids which cross the blood-brain barrier (BBB) via endothelial cell neutral carriers have long been a hallmark in studies of experimental ischemic pathology; there is likely a strong correlation between persistent protein synthesis inhibition and the progression of cell damage. Because the grafting procedure involves the loss of blood flow and the subsequent reperfusion of the donor tissue there are, mechanistically, important similarities to reversible ischemia models. The effects of ischemic injury on grafted CNS neurons are not fully understood. Quantitative analysis of grain distribution in individual graft or control (adjacent host cortex) neurons indicated an initial breakdown of the amino acid barrier system, subsequent recovery, and progressive reduction of amino acid uptake by 1 year. Up to 3 weeks after surgery grafts were flooded with the [(3)H]valine tracer but individual neurons contained relatively few silver grains. After this time, the tracer was normally distributed within graft neurons but at significantly lower levels than in controls. Grain density gradually decreased over time such that 12-month grafted neurons had approximately half that compared to control and only 58% of that in 2-month grafts; the 12-month levels were comparable to those observed at early (10 days) postoperative times. Autoradiography of immunostained sections for MAP-2, SMI 311 (neurofilament marker), and neuron-specific enolase showed reduced expression of these proteins in neurons coupled with weak amino acid tracer uptake. The results further suggest that grafted neurons bear intriguing similarities to neurons placed at ischemic risk, particularly "penumbral" neurons, which are affected by reduced blood flow and are metabolically weakened. The loss of BBB properties in early grafts may also extend to the endothelial cell amino acid carrier system, and the delayed revascularization process could affect neuronal uptake mechanisms.

Striatal matrix neurons of the rat differentiate in culture from dissociated fetal progenitor cells isolated by buoyant density centrifugation.

The adult striatum is composed of interlacing compartments known as patches (striosomes) and matrix, which differ with respect to a host of architectonic, biochemical and developmental parameters. We have exploited the 2-phase development of the striatum, employing buoyant-density fractionation to separate proliferating/undifferentiated neural precursors from the differentiated neurons of the E19 striatum. Primary cell cultures were established for the collected fractions, and immunohistochemistry for maturational and compartment-specific markers performed. The results indicate that the least buoyant, striatal precursors concentrate principally in the low buoyancy fraction of the gradient, and in culture express known matrix phenotype markers in an appropriate time frame.

Neural grafting reverses prenatal drug-induced alterations in hippocampal PKC and related behavioral deficits.

Administration of heroin or phenobarbital to pregnant mice evokes neurochemical and behavioral deficits consequent to disruption of septohippocampal cholinergic innervation. The present study evaluates the relationship between the drug-induced biochemical changes and the behavioral deficits, applying two different approaches: neural grafting and within-individual correlations of biochemistry and behavior. Mice were exposed transplacentally to phenobarbital or heroin on gestational days 9-18 and tested in adulthood. Drug-exposed mice displayed impaired radial arm maze performance, increases in presynaptic choline transporter sites (monitored with [(3)H]hemicholinium-3 binding), upregulation of membrane-associated protein kinase C (PKC) activity, and desensitization of the PKC response to a cholinergic agonist, carbachol. Grafting of cholinergic cells to the impaired hippocampus reversed the behavioral deficits nearly completely and restored basal PKC activity and the PKC response to carbachol to normal; the drug effects on hemicholinium-3 binding were also slightly obtunded by neural grafting, but nevertheless remained significantly elevated. There were significant correlations between the performance in the eight-arm maze and both basal PKC activity and PKC desensitization, and to a lesser extent, between behavioral performance and hemicholinium-3 binding. Taken together, these findings indicate an inextricable link between the biochemical effects of prenatal drug exposure on the PKC signaling cascade and adverse behavioral outcomes. The ability of neural grafting to reverse both the drug-induced changes in PKC and behaviors linked to septohippocampal cholinergic function suggest a mechanistic link between this signaling pathway and neurobehavioral teratology caused by heroin or phenobarbital.

Separation of dorsal and ventral dopaminergic neurons from embryonic rat mesencephalon by buoyant density fractionation: disassembling pattern in the ventral midbrain.

The dopaminergic neurons of the ventral mesencephalon, though physically mixed with non-dopamine neurons, are organized into dorsal and ventral 'tiers' with regard to their ontogeny, efferent projections and their relative position in the various mesencephalic sub-nuclei. We have employed buoyant density fractionation to separate the dopaminergic neurons of the two compartments and compare their subsequent phenotype development with respect to their expression of the gene encoding tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine biosynthetic pathway. Using immunocytochemistry, separately and combined with in situ hybridization, we demonstrate here that sedimentation of cell suspensions from E19 rat ventral mesencephalon on 5-step Percoll gradients produces cell fractions enriched in ventral and dorsal tier DA neurons, respectively.

Vascular, glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures.

Vascular endothelial growth factor is a highly conserved, heparin-binding protein which mediates a number of critical developmental processes in both vertebrates and invertebrates, including angiogenesis, vasculogenesis and hematopoiesis. We employed an organotypic rat explant model (produced from embryonic day 17 fetuses) to assess the effects of vascular endothelial growth factor on brain microvasculature in general and the ventral midbrain specifically. Immunohistochemistry using antisera to rat endothelial cell antigen and laminin demonstrated a robust, dose-dependent effect of vascular endothelial growth factor, resulting in increased vessel neogenesis, branching and lumen size by three days in vitro. This effect was blocked by addition of an anti-vascular endothelial growth factor antibody. At higher doses of vascular endothelial growth factor, the effect was attenuated, though a statistically significant increase in both astrocyte, and neuronal density was observed using antisera to glial and neuronal markers. Tyrosine hydroxylase-immunoreactive (i.e. dopaminergic) neurons, particularly, exhibited increased survival in response to vascular endothelial growth factor application. Vascular endothelial growth factor had a mitogenic effect on endothelial cells and astrocytes, but not dopaminergic neurons, as demonstrated by the addition of [3H]thymidine to the cultures 2 h after the cultures were established. Similarly, results of a radioreceptor assay indicated that specific vascular endothelial growth factor binding sites were present on blood vessels and astrocytes, and were up-regulated by exposure to vascular endothelial growth factor. We conclude that, in explants of the ventral mesencephalon, exogenously applied vascular endothelial growth factor is mitogenic for endothelial cells and astrocytes, and promotes growth/survival of neurons in general and dopaminergic neurons in particular.

Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo.

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell mitogen that has been shown to induce vasculogenesis and angiogenesis in many organ systems and tumors. Considering the importance of VEGF to embryonic vascularization and survival, the effects of administered VEGF on developing or adult cerebrovasculature are unknown: can VEGF alter brain angiogenesis or mature cerebrovascular patterns? To examine these questions we exposed fetal, newborn, and adult rat cortical slice explants to graduated doses of recombinant VEGF. The effects of another known angiogenic factor, basic fibroblast growth factor (bFGF), were evaluated in a comparable manner. In addition, we infused VEGF via minipump into the adult cortex. Significant angiogenic effects were found in all VEGF experiments in a dose-responsive manner that were abolished by the addition of VEGF neutralizing antibody. Fetal and newborn explants had a highly complex network of branched vessels that immunoexpressed the flt-1 VEGF receptor, and flk-1 VEGF receptor expression was determined by reverse transcription-PCR. Adult explants had enlarged, dilated vessels that appeared to be an expansion of the existing network. All bFGF-treated explants had substantially fewer vascular profiles. VEGF infusions produced both a remarkable localized neovascularization and, unexpectedly, the expression of flt-1 on reactive astrocytes but not on endothelial cells. The preponderance of neovascularization in vitro and in vivo, however, lacked the blood-brain barrier (BBB) phenotype marker, GLUT-1, suggesting that in brain the angiogenic role of VEGF may differ from a potential BBB functional role, i.e., transport and permeability. VEGF may serve an important capacity in neovascularization or BBB alterations after brain injury.

Calcium-binding proteins in the substantia nigra and ventral tegmental area during development: correlation with dopaminergic compartmentalization.

The importance of calcium in neuronal function has been amply demonstrated in recent years. The discovery of a class of proteins within neurons which bind calcium, therefore, has proven to be a catalyst for the generation of theories and hypotheses regarding mechanisms of neurotoxicity in the CNS. In addition, the distribution of certain calcium-binding proteins changes during neural development, suggesting that they may play a role in organization or pattern generation. We have examined the ontogeny of three related calcium-binding proteins, calbindin-D28, parvalbumin and calretinin, with respect to the ventral and dorsal compartments or tiers of the dopaminergic population in the ventral midbrain. Single and dual-label immunocytochemistry was employed to map the distributions of calcium-binding proteins and tyrosine hydroxylase from E18 through adulthood. The results show that each of the three proteins exhibits a unique developmental sequence and compartment preference, with calbindin D28 clearly related to the later-developing dorsal tier, and parvalbumin and calretinin to the ventral tier of the dopaminergic ventral mesencephalon.

Selective dopamine neurotoxicity by an industrial chemical: an environmental cause of Parkinson's disease?

While unproved, environmental toxins of industrial and or agricultural origin represent an attractive theory to explain the increasing incidence of degenerative diseases of the nervous system such as Parkinson's disease (PD). We have examined several chemicals utilized in an area of Israel previously demonstrated to contain a statistically greater than average number of people with Parkinson's disease. One of these agents, a light stabilizer employed universally in the production of polyolifins used in plastics, depleted primary mesencephalic cultures of dopamine neurons, and produced a dopamine-specific lesion of the substantia nigra pars compacta when injected stereotactically into the ventral midbrain of adult rats. The observed effects were dose-dependent. These findings represent a potentially significant development in the search for industrial/environmental causes of neurodegenerative disease.

Neural grafting as a tool for the study and reversal of neurobehavioral birth defects.

The transplantation of fetal neurons has gained notoriety in recent years for its perceived potential to reverse neurological deficits caused by loss of one or another neuronal population. The present paper describes a neural grafting approach employed by our laboratory to gain more insight into the drug-induced neurobehavioral teratogenicity. Mice were exposed prenatally to phenobarbital by feeding the barbiturate to the pregnant dam on gestation days 9-18. Heroin exposure was accomplished by injecting dams during the same gestational period. At maturity, the drug-exposed offspring displayed profound deficits in specific behavioral tasks, suggesting alterations in the septohippocampal cholinergic pathway. Biochemically, we observed increased presynaptic activity in the pathway, which was not accompanied by a corresponding reduction in postsynaptic activity. Rather, there was a general hyperactivation along the different postsynaptic phases. In contrast, we noted a desensitization of protein kinase C activity in response to the exposure of a cholinergic agonist to the drug-exposed offspring. Subsequent transplantation of embryonic cholinergic cells from normal mice to the impaired hippocampus reversed the behavioral deficits, whereas sham-operated controls exhibited no improvement. Concomitantly, all the biochemical alterations studied, both presynaptic and postsynaptic, were either partially or completely reversed following grafting.

An avian model for the reversal of 6-hydroxydopamine induced rotating behaviour by neural grafting.

A new animal model of parkinsonism was established in 'Black Silkie' chickens by means of unilateral injections of 6-hydroxy-dopamine into the substantia nigra. Apomorphine produced a strong contralateral turning pattern in the lesioned chickens, amphetamine had no effect. 6-OHDA treated animals received embryonic transplants of substantia nigra cell suspensions which caused them to cease rotating (P < 0.01). This finding allows us to add an avian model, which offers unique methodological advantages, for reversal of 6-OHDA-induced rotating behavior by transplantation.

Metabolic profile of fetal dopamine neurons transplanted to the adult rat striatum.

In the present study, we have examined the expression and distribution of the metabolic marker neuron-specific enolase (NSE) in solid-tissue transplants of fetal substantia nigra (SN) to the striatum of intact and 6-hydroxydopamine lesioned mature rats. Immunocytochemistry was applied to label NSE and tyrosine hydroxylase (TH) respectively. Cellular content of NSE is indicative of metabolic activity as well as synaptogenesis/maturation. Three months after implantation, the fetal grafts exhibited intensely TH-immunoreactive neurons, typically organized in elongated clusters, especially along the graft-host border and along blood vessels penetrating into the graft interior. Moderate to high metabolic activity as indicated by NSE immunoreactivity was observed in neuronal perikarya, principally in non-TH immunoreactive areas. In contrast to these immunohistochemical findings, in situ hybridization for TH mRNA, carried out exclusively on grafts into the intact striatum, demonstrated DA cell bodies both at the graft-host interface and, significantly, throughout the graft interior. The number of transcripts per cell, moreover, did not differ significantly in these two locations. We propose that conditions at the graft-host border promote tissue-specific regulation of nigral DA neurons, and that this regulation occurs post-transcriptionally. Thus, DA neurons relatively distant from the host parenchyma are underregulated, resulting in a higher level of metabolic activity and an increased turnover of TH in the grafted neurons.

Prenatal ontogeny of tyrosine hydroxylase gene expression in the rat ventral mesencephalon.

We have examined the development of dopaminergic (DA) neurons in the embryonic mesencephalon with regard to the expression of the gene coding for tyrosine hydroxylase (TH). Mesencephalic DA neurons from rat embryos aged E13 to E21 were analyzed using a quantitative in situ hybridization protocol featuring a 35S-labeled RNA probe complimentary to TH mRNA. In the early-to-mid stage embryonic brains, the expression of the TH gene was examined relative to the position of individual, migrating DA cells in the caudal-rostral and dorsal-ventral axes of the mesencephalon. In the later embryonic subjects, neurons were analyzed according to their position in one of the midbrain DA nuclei. The ontogeny of TH gene expression in the rat mesencephalon exhibited two phases: during the early phase (E13-E15), we observed major fluctuations in the level of TH gene expression accompanying the differentiation and maturation processes of the DA cells. Later, in the mid-to-late gestation fetus (E18-E21), TH gene expression generally stabilized as TH mRNA-expressing neurons reached their final anatomical positions within the mesencephalic DA complex. Our data demonstrate the complex dynamics which characterize the ontogeny of TH gene expression in the prenatally developing mesencephalon, and suggest a connection between the maturational level of DA neurons and the expression of the key gene regulating their principle neurotransmitter.

Differential expression of tyrosine hydroxylase mRNA in the developing rat mesencephalon.

1. With respect to the mesostriatal projection, the mesencephalon is composed of two dopaminergic (DA) cell populations, called dorsal tier and ventral tier. Strong evidence suggests differences in both the spatial and the temporal sequence of the innervation of the striatum between the two groups, with the ventral tier neurons innervating striatal patches prenatally and dorsal tier cells innervating striatal matrix postnatally. 2. Using in situ hybridization, we have examined the expression of the gene coding for tyrosine hydroxylase (TH) in mesencephalic DA neurons with respect to their postnatal development. Two ontogenic patterns of expression were observed: (a) dorsal tier neurons of the medial mesencephalon exhibited a sharp increase in expression beginning after birth, peaking on day 14, then decreasing and, finally, stabilizing; and (b) ventral tier neurons and dorsal tier cells from the lateral and the medial-dorsal mesencephalon showed only a slight increase in TH mRNA, reaching a plateau at P10. 3. The time course of the observed increase in TH gene expression in the first group, generally parallels the innervation of their target cells in the striatal matrix, suggesting that TH gene expression in these cells may be influenced by their postsynaptic cells or by the innervation process.

Temporal and compartmental restriction of neuron-specific enolase expression in the rat mesostriatal system.

The striatum and the mesencephalic dopamine neurons which innervate it, are each organized into developmentally and biochemically distinct compartments. Striatal patches, characterized in the neonate by high concentrations of opiate receptors and substance P, are innervated prenatally by fibers originating in one group of midbrain dopamine neurons, the ventral tier. By the third postnatal day, a dense dopamine projection from neurons in the dorsal tier of the mesostriatal group innervates non-patch areas of the striatum, i.e. the matrix, and is followed by the appearance there of neurotensin, somatostatin and calcium binding protein. We have recently observed that the period of establishment of connections between dorsal tier dopamine neurons and their target cells in the striatal matrix is accompanied by a surge in expression of the gene coding for tyrosine hydroxylase (TH). In order to determine the overall metabolic state of mesencephalic and striatal neurons during the period of up-regulation of TH gene expression, we have applied immunocytochemistry for neuron specific enolase (NSE), and cytochrome oxidase histochemistry, known markers for neuronal activity, as well as TH immunohistochemistry to the mesencephalon and striatum of postnatally developing rats. At birth, both NSE and cytochrome oxidase were expressed almost exclusively in the patches, appearing in the matrix only after the 2nd postnatal day. Patches of NSE remained visible thru the 14th day. In the mesencephalon, cytochrome oxidase and immunoreactive NSE cells in adjacent sections, were present only in the pars reticulata (i.e. ventral tier). By day 8, both techniques identified nigral cells in the dorsal as well as ventral tiers.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuron-specific enolase reflects metabolic activity in mesencephalic neurons of the rat.

Numerous studies on the local rate of energy metabolism of various brain regions during development and following experimental manipulation have been conducted using 2-deoxyglucose uptake and cytochrome oxidase (CO) histochemistry, both considered to be reliable indicators of long-term and short-term alterations in neuronal activity, respectively. Another method which has been related to neuronal activity is neuron-specific enolase (NSE) immunohistochemistry. An isoenzyme of enolase, a key element in the glycolytic pathway, NSE is present in neurons and neural-related cells e.g. neuroendocrine cells, pituicytes, and many tumor cells, but not in glia. The distribution on adjacent tissue sections of immunoreactive NSE and histochemically determined CO were mapped in the rat mesencephalon and adrenal medulla. Both methods showed highly restricted localization of staining which coincided with few exceptions in the most reactive areas, namely the superior colliculus, medial and lateral geniculate nuclei, red nucleus, lateral mammillary nucleus, interpeduncular nucleus and substantia nigra pars lateralis and pars reticulata. Immunoreactivity of varying intensity for NSE was also observed in perikarya and in processes of numerous scattered neurons throughout the mesencephalon, including the substantia nigra pars compacta, and reticular formation. The general correspondence in staining patterns between CO and NSE in the midbrain, supports the utility of NSE as a useful index of metabolic activity in neurons.

Ultrastructural changes in magnocellular neurons from the supraoptic nucleus of aged rats.

Magnocellular neurosecretory neurons in the supraoptic nucleus were examined in aged and young subjects to assess the ultrastructural correlates of cellular activity including cell, nuclear and nucleolar size, as well as the percentage of the cell occupied by Golgi, mitochondrial and rough endoplasmic reticulum compartments. Morphometric analysis was performed on arbitrarily selected cell profiles using a computerized morphometry protocol. Approximately 50% of those neurons examined from aged subjects exhibited a statistically significant increase relative to the young rats in total cell area and all cellular organelles examined except nuclear area. Moreover, an increase in the number and density (per unit membrane area) of synaptic contacts onto those neurons was observed. These findings suggest an increase in synthetic activity by a subpopulation of supraoptic magnocellular neurons, and support the concept of neuronal plasticity in aged rats.

Physiological and biochemical indices of neurohypophyseal function in the aging Fischer rat.

In order to resolve conflicting reports in the literature on the effect of aging on the hypothalamo neurohypophyseal system (HNS) in rats, multiple parameters associated with the HNS were evaluated in young (4 months), fully mature (14 months), and old (25 months) Fischer 344 rats under basal and stimulated conditions. The hypothalamic hormones oxytocin and vasopressin were compared in radioimmunoassay of serum, urine, brain and pituitary. Information on body weight, water intake, urine output, serum hematocrit and plasma osmolality was also obtained from the same subjects and analyzed together with these data. Finally, semi quantitative histofluorescence assessment of the noradrenergic innervation of the mediobasal hypothalamus from the same animals was performed to determine the extent of central afferent input to the HNS with advancing age. The circulating levels of vasopressin and oxytocin did not significantly differ in the three age groups under basal conditions. Serum vasopressin concentration was increased following water deprivation, and the increase was comparable in all age groups. Serum oxytocin was also increased following water deprivation in all groups, but the increase was greater in the 25-month-old rats relative to the 4-month-old rats. Urinary excretion of vasopressin was used as an index of daily vasopressin secretion. The urinary concentration of vasopressin was less in aged rats relative to young controls, though an increased urine volume in the mature and old animals meant that total vasopressin excretion in the urine was comparable at all ages studied. The increased urine volume in the mature and aged rats does not appear to reflect a decrease in renal sensitivity to vasopressin, since all age groups demonstrated a comparable reduction in urine volume during water deprivation, at comparable concentrations of circulating vasopressin. These data suggest that the increase in urine volume observed in the 14- and 25-month-old rats may be a function of increased fluid intake rather than hyperactivity in the HNS. The concentrations of both peptides were reduced in the posterior pituitary of aged rats, though again, the total amount of peptide in the gland did not change. Only oxytocin showed an age-related change in the hypothalamus, decreasing in the oldest subjects. These data indicate that the ability to secrete adequate quantities of vasopressin in response to dehydration is not compromised in Fisher 344 rats up to 25 months of age.

Expression of tyrosine hydroxylase mRNA in transplanted fetal dopamine neurons.

Expression of genes coding for synthesis of secretory products has been shown to be an important index of neuronal activity. Gene expression in transplanted fetal substantia nigra (SN) was examined for the first time, utilizing in situ hybridization with a probe for tyrosine hydroxylase mRNA. Three months after implantation, the grafts contained many labeled neurons. Compared to host SN neurons, the grafted dopaminergic cells expressed more message for the enzyme, while they showed lower amounts of the enzyme itself. This result suggests that a molecular approach applied to neural transplantation can detect important if subtle differences in graft cell activity.