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J P Herman

Publications and source records attributed to J P Herman.

At least 73 records · Page 4Linked to original sources
PubMed1994

Tear film lipid layer thickness as a function of blinking.

Alterations in the tear film lipid layer as a function of blinking were investigated using a custom-designed specular reflection monitoring system. The tear film lipid layer of 104 subjects under conditions of normal ("baseline") blinking and "forceful" blinking was quantitated on the basis of specific interference colors. Deliberate, forceful blinking was found to significantly increase the lipid layer thickness (LLT) of the tear film. The magnitude of increase was found to be correlated with the baseline LLT values; individuals with baseline LLT values of 75-150 nm demonstrated a mean increase in LLT of 33 nm following forceful blinking, whereas subjects with baseline LLT values < or = 60 nm experienced a mean increase of 19 nm. The difference in the magnitude of increase between the groups was highly significant (p = 0.0001). The data suggest that, in addition to playing a role in the spreading of lipid across the tear film, the blinking mechanism may be important in the maintenance of the lipid layer by augmenting the expression of lipids from the meibomian glands.

Adolescent↗
PubMed1994

Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression.

The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA-producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region.

Adrenocorticotropic Hormone↗
PubMed1994

Differential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain.

CRH mRNA was detected by in situ hybridization histochemistry in numerous regions of the adult mouse brain, including most prominently the paraventricular nucleus (PVN) of the hypothalamus, the inferior olivary nucleus, and Barrington's nucleus. After adrenalectomy, steady state CRH mRNA levels increased 1.7-fold, specifically in the PVN, consistent with reports of negative glucocorticoid regulation of CRH expression in the rat PVN. Ontogenetic analysis of CRH expression in fetal and neonatal mouse brain demonstrated CRH mRNA in PVN, Barrington's nucleus, olivary complex, and amygdaloid primordia on embryonic day 13.5. In contrast, CRH mRNA was not detectable in the cortex until after birth. CRH expression also exhibited differential regulation in ontogeny. CRH mRNA reached adult levels at markedly different times of development in each brain region, and CRH expression was reduced specifically in the PVN just before birth and the stress hyporesponsive period. High levels of CRH mRNA were present transiently in the developing lung and celiac ganglion. The novel findings of CRH expression in fetal lung during the period of glucocorticoid-induced lung maturation and in celiac ganglion during development of the sympathetic nervous system indicate that CRH may have some important developmental functions in addition to its role in activation of the stress response.

Adrenalectomy↗
PubMed1993

Ventral subicular interaction with the hypothalamic paraventricular nucleus: evidence for a relay in the bed nucleus of the stria terminalis.

The axonal projections of the ventral subiculum to the bed nucleus of the stria terminalis (BST) were examined in the rat with the anterograde neuronal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Axons originating in the ventral subiculum coursed to the BST through either the fimbria-fornix, or a pathway involving the stria terminalis via the amygdala. Ventral subicular axons gave rise to dense terminal networks that were preferentially distributed in medial and ventral subregions of the BST. The distribution of subicular fibers and terminals was examined in relation to BST neurons that project to the hypothalamic paraventricular nucleus (PVN). In these cases, discrete iontophoretic injections of the retrograde tracer Fluoro-gold were made in the PVN, with PHA-L delivered to the ipsilateral ventral subiculum. An immunocytochemical double-labeling protocol was then employed for the simultaneous detection of PHA-L and Fluoro-gold, and provided light microscopic evidence for subicular input to PVN-projecting cells located within the BST. In a second series of experiments, the gamma-amino butyric acid (GABA)ergic nature of the BST was examined by in situ hybridization histochemistry for detection of transcripts encoding GAD67 mRNA. The studies revealed that a high proportion of BST neurons express GAD67 transcripts. Also, experiments combining Fluoro-gold tracing with GAD67 in situ hybridization suggested that a proportion of PVN-projecting neurons in the BST are GABAergic. Taken together, the results of these sets of studies suggest that the inhibitory influences of the hippocampus on the PVN might be relayed through specific portions of the BST. These findings may have important implications for our understanding of the neural regulation of the hypothalamic-pituitary-adrenal axis.

Amygdala↗
PubMed1993

Intrastriatal transplants of embryonic dopaminergic neurons counteract the increase of striatal enkephalin immunostaining but not serotoninergic sprouting elicited by a neonatal lesion of the nigrostriatal dopaminergic pathway.

The aim of the our experiment was to compare the ability of intrastriatal implants of embryonic dopaminergic neurons to reverse two kinds of postlesion modification in the host brain: the change in the activity level of neurons in the denervated area and morphological modifications, e.g. collateral sprouting. The ascending dopaminergic system of 3-day-old rat pups was unilaterally lesioned by an intrahypothalamic injection of the neurotoxin 6-hydroxydopamine. This lesion has been described previously to induce an increase in the level of activity of striatal enkephalinergic neurons. The same lesion leads also to sprouting of the serotoninergic afferents in the striatum, leading to hyperinnervation of this structure. The existence of these modifications thus offers the possibility of testing the influence of grafts in one structure of the same animal on two lesion-induced reactions of different nature. A cell suspension obtained from mesencephali of embryonic day 14 rats and containing dopaminergic neurons was implanted into the denervated striatum of lesioned animals 5 days after the lesion. Nine months later the animals were killed and immunohistochemistry was performed on striatal sections using antibodies directed against tyrosine hydroxylase, methionine enkephalin and serotonin. Intensity of immunostaining (methionine enkephalin and serotonin) as well as innervation density (serotonin) was quantified through the use of a computer-assisted image analyser. The lesion led to the disappearance of striatal dopaminergic innervation. Implanted dopaminergic neurons were found scattered in the striatum and restored a dopaminergic innervation in a large portion of this structure. There was a marked increase in striatal methionine enkephalin immunostaining in lesioned animals, which was most pronounced in the dorsolateral part of the striatum (+ 150% compared to control values), while in the ventral part it was slight or non-existent. The density of striatal serotoninergic innervation was also increased by approximately 250% relative to control values. In grafted animals striatal enkephalin immunostaining was similar to that observed in control animals. On the other hand, the serotoninergic hyperinnervation was still present in the graft-bearing striata. These results suggest that while intrastriatal implants of embryonic dopaminergic neurons are able to counteract modifications in the functioning of local striatal neuronal systems such as the increase in enkephalinergic activity or receptor hypersensitivity occurring as a result of the lesion, they might be unable to reverse postlesion morphological modifications.

Animals↗
PubMed1993

Developmentally regulated and spatially restricted antigens of radial glial cells.

Radial glial cells, present in many parts of the embryonic vertebrate central nervous system (CNS), have been implicated in the guidance of neuroblasts from the ventricular zone to their laminar destinations. Moreover, radial glial cells may be progenitors of some CNS neurons and glia. To gain new insight into the structure and development of these cells, we have generated and characterized a panel of monoclonal antibodies that recognize radial glial cells of the chick optic tectum. Mice were immunized with homogenates of embryonic day (E) 10 tectum, and antibodies were analyzed by immunofluorescence and immunoblotting. We describe here three pairs of antibodies. 1) H5 and a previously generated antibody, R5 (Dräger et al., J. Neurosci. 4:2025, 1984), stain the whole extent of the radial glial cell from E7 to E20. In cultures prepared from E10 tecta, both stain a filamentous meshwork in glial cells but not in neurons. On immunoblots, both recognize a protein of approximately 52 kD that is closely related (or identical) to vimentin. 2) H28 and H29 stain radial glia between E7 and E14, but not later. Moreover, H28 and H29 staining is markedly more intense in the ventricular and intermediate zones than in the laminae of the tectal plate. Both of these antibodies recognize an intracellular epitope in cultured glial cells and a protein of approximately 35 kD on immunoblots. 3) H2 and H27 recognize antigens concentrated in the most superficial processes and endfeet of radial glia in late (E16-E20) embryos. They stain distinct structures in cultured glia, suggesting that they recognize distinct antigens. H27 recognizes a protein of approximately 29 kD on immunoblots. Thus antibodies H5 and R5 are good markers of radial glial cells at all stages, whereas the others define antigens that are developmentally regulated and localized to discrete domains. Together, these antibodies can be used to study temporal and spatial specializations of radial glia.

Animals↗
PubMed1993

Regulation of adrenocorticosteroid receptor mRNA expression in the central nervous system.

1. The adrenocorticosteroid receptors are hormone-activated transcription factors that have the potential to influence gene expression in a wide variety of CNS neurons. This review summarizes the present state of knowledge regarding the localization and regulation of glucocorticoid (or type II corticosteroid) receptor and mineralocorticoid (or type I corticosteroid) receptor mRNAs in brain, from the perspective of their potential influence on a wide variety of hormone-responsive genes. 2. Corticosteroid receptors are widely but not uniformly localized in the CNS and exhibit very complex regulation by glucocorticoids, gonadal steroids, neurotransmitter systems, and endogenous circadian drive. Both receptor species are present during development, implying an ability for these transcription factors to interact with neuronal differentiation, growth, and viability, and both receptors appear to regulate with age, suggesting relationships between adrenocorticosteroid receptor populations and brain aging. Regulation of adrenocorticosteroid receptor mRNA expression at the level of polyadenylation and splicing indicates that GR and MR biosynthesis is a dynamic process susceptible to numerous classes of information. 3. Further study of GR and MR biosynthesis at the gene, mRNA, and protein level is required to determine the true meaning of the regulatory complexities seen in defined neuronal circuits.

Aging↗
PubMed1993

Transplantation of fetal nigral cells reverses the increase of preproenkephalin mRNA levels in the rat striatum caused by 6-OHDA lesion of the dopaminergic nigrostriatal pathway: a quantitative in situ hybridization study.

Unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine (DA) pathway causes a significant increase of preproenkephalin (PPE) messenger RNA (mRNA) levels in the DA-depleted striatum in rat brain. Using an in situ hybridization (ISH) technique and computer-assisted microdensitometry, we quantified the changes in PPE mRNA levels in the striatum. Seven months after lesion, levels of PPE mRNA were 75% higher in the DA-depleted striatum than in the contralateral control striatum of the same animal or in the striatum of sham control animals. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a complete reversal of this increase and, in grafted animals, levels of PPE mRNA were at control values. Moreover, this reversal extended beyond the areas reinnervated by the grafted dopaminergic neurons.

Animals↗
PubMed1993

Effects of intracerebral dopaminergic grafts on behavioural deficits induced by neonatal 6-hydroxydopamine lesions of the mesotelencephalic dopaminergic pathway.

The functional capabilities of dopamine neuron-rich grafts implanted into the accumbens and striatal regions in neonatal rats were evaluated in a series of behavioural tests. The ascending mesotelencephalic dopaminergic system of three-day-old rat pups was bilaterally lesioned by injecting 6-hydroxydopamine at the level of the lateral hypothalamus. Five days later a suspension containing dopaminergic neurons obtained from embryonic day 14 mesencephali was injected bilaterally into the striatal complex. The functional effects of such grafts were evaluated using behavioural tests for which it was known that the performance of the animals is changed following the lesion of the mesotelencephalic pathway and for which the influence of dopaminergic grafts implanted into adult hosts have previously been described. The dopamine-rich grafts compensated for the modifications of the locomotor responsiveness to amphetamine and apomorphine induced by neonatal dopamine depletion. However, the grafts were unable to restore more complex behaviours such as hoarding for food pellets, schedule-induced polydipsia and learning behaviours. Moreover, the neonatal transplants induced additional deficits such as catalepsia, nocturnal hyperactivity and day-time hyperactivity during food deprivation. It was concluded that, at least in the present paradigm, the implantation into neonatal brain does not lead to any greater functional recovery than that observed after implantation during adulthood.

Animals↗
PubMed1993

Mechanisms of amphetamine-induced rotation in rats with unilateral intrastriatal grafts of embryonic dopaminergic neurons: a pharmacological and biochemical analysis.

Amphetamine induces a pronounced rotation directed ipsilateral to the lesion and lasting about 2 h in rats bearing a unilateral lesion of the nigrostriatal dopaminergic pathway. Implantation of embryonic dopaminergic neurons into the lesioned striatum leads to a compensation of this rotation. However, graft-bearing animals display a strong biphasic contralateral rotation, lasting up to 5 h. To try to ascertain the mechanisms of this anomalous rotation, two separate experiments were performed. First, we tested whether the contralateral rotation presented by the grafted animals could be correlated to the persistence of the lesion-induced decoupling of striatal D1 and D2 receptors. Lesioned and grafted animals were submitted to a series of four amphetamine (5 mg/kg, i.p.) rotation tests. Preceding each test animals received, in a randomized order, one of four of the following treatments: physiological saline, a D1 receptor blocker (SCH-23390, 0.1 mg/kg, s.c.), a D2 receptor blocker (raclopride, 2.5 mg/kg, i.p.) or the combination of the D1 and D2 antagonists. The ipsilateral rotation observed in the lesioned animals was abolished by the separate blockade of both classes of dopamine receptor as well as by their combined blockade. Grafted animals could be separated into two subgroups, based on the effect of the antagonists during the first 2 h of amphetamine-induced rotation. In one subgroup, antagonists had the same effect on the amphetamine-induced contralateral rotation as they did on the ipsilateral rotation displayed by lesioned animals. In this group, D1 and D2 receptors were therefore recoupled by the implant in the lesioned striatum. In the other subgroup, the contralateral rotation could be antagonized only by the combined D1 and D2 blockade, while the separate blockade of D1 or D2 receptors did not decrease or even increased the amphetamine-induced rotation. This indicates that in this group the lesion-induced decoupling of D1 and D2 receptors persisted. Nevertheless, the characteristics of the amphetamine-induced rotation (magnitude, duration) were the same in the two subgroups. Likewise, hypersensitivities of both D1 and D2 receptors were completely abolished by the graft in both subgroups. From this experiment it is concluded that the amphetamine-induced rotation observed in grafted animals is not correlated with the state of coupling of striatal D1 or D2 receptors. In a second experiment, dopamine release was monitored by microdialysis in the graft-bearing and the contralateral normal striatum of awake, behaving animals following the administration of amphetamine to test whether the observed rotation could be explained by a higher than normal dopamine release from the implanted dopaminergic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamine↗
PubMed1993

Localization of C-type natriuretic peptide mRNA in rat hypothalamus.

Central or peripheral administration of C-type natriuretic peptide (CNP) affects numerous neuroendocrine systems, including the hypothalamo-pituitary-gonadal, hypothalamo-pituitary-adrenocortical and hypothalamo-neurohypophysial axes. The present report characterizes the distribution of CNP mRNA in hypothalamus, providing the first definition of CNP-containing neuroendocrine circuits. In situ hybridization histochemical analysis revealed high expression of CNP mRNA in the anteroventral periventricular nucleus (AVPv) and in hypothalamic arcuate nucleus (ARC). Hybridization signals of significantly lower intensity were seen in the medial, median and periventricular preoptic area, the supraoptic, dorsomedial, ventral premammillary and lateral mammillary nuclei and in the posterior hypothalamic area. A few scattered CNP mRNA containing cells were visualized in the medial parvocellular paraventricular nucleus, posterior magnocellular paraventricular nucleus and lateral hypothalamic area. In the AVPv and ARC the pattern of CNP mRNA distribution paralleled that of ANP mRNA. The results indicate a distribution of CNP mRNA associated with key neuroendocrine systems, and underscores the potential importance of this novel natriuretic peptide in neuroendocrine regulation.

Animals↗
PubMed1992

Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression.

The hippocampus appears to be involved in tonic regulation of the hypothalamo-pituitary-adrenocortical axis via interactions with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular nucleus (PVN). To further investigate the anatomical basis of such interactions, lesions were made to forebrain fiber tracts in position to communicate inhibitory information from the hippocampus to the PVN. Total fimbria-fornix transections (TFF) and lateral fimbria-fornix lesions (LFF) both significantly increased CRH mRNA levels in the medial parvocellular PVN, as assayed by semi-quantitative in situ hybridization histochemistry. Medial fimbria-fornix lesions or section of the medial corticohypothalamic tracts (MCHT) did not influence CRH mRNA levels. The LFF group showed increases in both AVP mRNA and ACTH secretion, whereas no other lesion was effective in this regard. The results suggest: (1) hippocampal efferents conferring tonic inhibition of the HPA axis probably originate in regions contributing to the lateral extent of the fornix, representing structures in the ventral subiculum and ventral extent of CA1; (2) projections from the hippocampus to the medial basal hypothalamus (travelling in the MCHT) are unlikely to affect HPA function; (3) hippocampus may influence the PVN CRH/AVP neuron at multiple levels, in that LFF and TFF lesions have differential effects on PVN AVP mRNA levels and ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1992

Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: an autoradiographic study.

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxydopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1 agonist compound SKF 38393 (2.5 mg/kg) or of the D2 agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1 and D2 dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1 receptors was not significantly affected while the density of D2 receptors was increased by about 25-50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1 receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2 receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2 receptors.

Animals↗
PubMed1992

Rapid regulation of corticotropin-releasing hormone gene transcription in vivo.

Regulation of corticotropin-releasing hormone (CRH) gene expression in vivo was assessed via in situ hybridization histochemistry, using probes directed against an intronic sequence of the CRH gene. Initial characterization of the CRH intron (CRHin) probe revealed specific localization of signal to the nuclear compartment of neurons in the medial parvocellular paraventricular hypothalamus, which are known to produce CRH peptide and mRNA. Abundance of CRHin signal was low, commensurate with a low resting pool of CRH heteronuclear RNA (hnRNA), representing CRH primary transcript. Regulation of CRH hnRNA levels was assessed after acute glucocorticoid synthesis blockade by injection of metyrapone. Metyrapone inhibits the conversion of 11-deoxycorticosterone to corticosterone, thereby rapidly depleting glucocorticoids and serving as a discrete stimulus for hypothalamo-pituitary-adreno-cortical activation. Plasma hormone measurements verified the efficacy of treatment, as metyrapone-treated rats showed extremely low basal corticosterone levels at all postinjection time points, while exhibiting progressive increases in plasma ACTH release over the 60-min postinjection period. CRH hnRNA levels were markedly increased 15-30 min after metyrapone injection, consistent with a rapid induction of CRH gene transcription in response to the stimulatory event. CRH mRNA, on the other hand, did not exceed control levels until 60 min post metyrapone, illustrative of a temporal lag between transcriptional changes and detectable changes in mRNA pools. Additional sections from metyrapone-and vehicle-treated rats were hybridized with probes complementary to mRNA encoding the immediate-early gene c-fos. c-fos was not present under unstimulated conditions yet was rapidly induced upon metyrapone treatment or vehicle injection (15 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Lesions of parvocellular subdivisions of the hypothalamic paraventricular nucleus alter open field behavior and acquisition of sensory and spatial discrimination.

Rats with ibotenic acid (IBO) lesions of the hypothalamic paraventricular nucleus (PVN) were compared with operated control animals over a battery of tests designed to assess memory- and arousal-related behavioral processes. At the dose employed in these experiments, ibotenic acid selectively destroys parvocellular elements of the PVN, leaving magnocellular subdivisions relatively intact, allowing for experimental dissection of the influence of parvocellular and magnocellular PVN neuronal populations on the behavioral parameters measured. IBO-treated rats showed a greater incidence of rearing behavior and exhibited greater levels of total and central ambulation in an open field than control rats. Acquisition of both the sensory and spatial reward contingencies were retarded in the IBO-lesion group; however, no differences were evident between IBO-treated and control groups in an approach-avoidance test, nor in the ability to perform the spatial and sensory discrimination tasks to a criterion level of accuracy. Histological examination verified that bilateral IBO lesions destroyed parvocellular elements of the PVN, while sparing the majority of magnocellular neurons. Results suggest that parvocellular PVN lesions alter behavioral performance via interactions with physiological systems governing arousal level.

Analysis of Variance↗
PubMed1991

Anatomical and behavioral comparison of unilateral dopamine-rich grafts implanted into the striatum of neonatal and adult rats.

The anatomical and functional characteristics of dopamine neuron-rich grafts implanted into rat pups were compared with those of identical grafts implanted into adult hosts. The host nigrostriatal dopaminergic pathway was unilaterally destroyed by an intrahypothalamic injection of 6-hydroxydopamine. This was followed five days later by the implantation of a cellular suspension obtained from rat embryonic mesencephali. Identical operations were carried out on adult and infant (PD3) rats. The survival rate of implanted tyrosine hydroxylase-positive cells was lower in the neonates. On the other hand, in the neonate hosts, surviving immunoreactive cells migrated extensively throughout the host striatum coursing preferentially below the corpus callosum and towards the subependymal zone. The structural integrity of the host parenchyma was well maintained after the neonatal implantation, in contrast to that observed in the adults. Despite a difference in the cell survival rate, there was no major difference in reinnervation density between the two types of host. The functional capacities of the implants were evaluated by measuring the rotational responses of the animals to dopaminergic agonists. The implants compensated the lesion-induced contralateral rotational response to the mixed agonist apomorphine and the D1 agonist SCH-38393 in both neonates and adults. However, the response to the D2 agonist LY-171555 was not significantly attenuated by the implant. The ipsilateral rotational response to amphetamine observed in the lesioned animals was also compensated and even reversed by the graft. It is concluded that with respect to rotational behavior, similar functional benefits were observed following adult stage or neonatal implantation, despite differences in their anatomical development.

Amphetamine↗
PubMed1991

Increase of striatal methionin enkephalin content following lesion of the nigrostriatal dopaminergic pathway in adult rats and reversal following the implantation of embryonic dopaminergic neurons: a quantitative immunohistochemical analysis.

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced dysfunction of striatal enkephalinergic neurons, one of the major output systems of the striatum. The ascending dopaminergic pathway of adult rats was unilaterally lesioned. Three weeks later a cell suspension obtained from the mesencephali of ED14 rat embryos was implanted into the denervated striatum and striatal methionin enkephalin immunostaining was quantified six months later by the use of an image analyser. Methionin enkephalin immunostaining was unevenly distributed in the striatum of control animals. Besides the classical patch/matrix pattern, a mediolateral gradient was also present and, moreover, immunostaining decreased towards caudal levels. Seven months after the lesion of the nigrostriatal dopaminergic pathway, methionin enkephalin immunostaining was found to be increased in the denervated striatum by about 50%. However, relative increases were more sustained in the areas where basal methionin enkephalin immunostaining were lowest, i.e. the lateral striatum and posterior striatal areas. This resulted in an attenuation of the global gradients seen in the normal striatum. Increased immunostaining was also found in the ipsilateral globus pallidus. The implantation, into the denervated striatum, of embryonic dopaminergic neurons led to a reversal of the lesion-induced increase of striatal and pallidal methionin enkephalin immunostaining six months later. Moreover, this reversal resulted in an overshoot, as the level of immunostaining in the graft-bearing striatum was found to be lower than the levels found in the normal striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the function of one of the major output systems of the striatum and, through it, influence more distant targets of this structure. This suggests a physiological basis for the behavioral effects observed previously with such grafts.

Animals↗