Biomedical subjects

A Seiger

Publications and source records attributed to A Seiger.

At least 19 recordsLinked to original sources

PubMed2005

Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum.

Prenatal nicotine exposure is associated with an increased risk of complications during pregnancy and childhood. In this study the expression of nicotinic and muscarinic acetylcholine receptors in first trimester pons, medulla oblongata and cerebellum from abortus (5-12 weeks of gestation) of smoking and nonsmoking women was compared. A significant age-related increase in binding of nicotinic receptor subtype alpha4 was found in both pons and cerebellum only in fetal tissue from non-smoking women, while a similar increase was observed in medulla oblongata from fetuses exposed to smoking. A significant age-related increase in binding of muscarinic receptor subtype m2 was observed in pons from abortus of smoking compared with non-smoking women. The gene expression pattern of both alpha4 and alpha7 nicotinic receptor subunits was changed after smoking in all three regions investigated. Smoking also changed the expression of m1 and 2 muscarinic receptor mRNA in pons, m1 mRNA in cerebellum and the m3 mRNA in medulla oblongata. The findings indicate that early prenatal nicotine exposure affects the normal developmental pattern of the cholinergic system in human fetal brain.

Alkaloids↗

PubMed2004

Distribution of presenilin 1 and 2 and their relation to Notch receptors and ligands in human embryonic/foetal central nervous system.

Notch signaling in vertebrates is mediated by four Notch receptors (Notch-1, -2, -3, and -4) that are activated by interacting with at least five different Notch ligands, Jagged-1, Jagged-2, Delta-1, -2, and -3. Recent studies have shown that the gamma-secretase-like intramembranous cleavage of Notch receptors to release their cytoplasmic signaling domains requires the presenilin (PS) proteins 1 and 2 (PS1 and PS2). Here, we used immunohistochemistry to compare the distribution of all four Notch receptor proteins and three ligands in the context of co-localization with PS1 and PS2 in first trimester human central nervous system (CNS). In addition, we investigated Notch receptors and ligands expression by Western blotting. The study was performed on the forebrain and spinal cord of human embryonic/foetal CNS (5-11 gestational weeks). Results showed a divergent distribution of the different Notch receptor proteins with only Notch-1 being co-localized with PS1 and PS2. Notch-2 was only seen occasionally within the developing cortex and spinal cord. Notch-3 expression was restricted to neuroepithelial cells of the spinal cord and endothelial cells in blood vessels of both developing cerebral cortex and spinal cord. The weak, punctate staining of Notch-4 in the neuroepithelium of the spinal cord could not be confirmed with Western blotting. Neither Notch-2, nor -3 showed overlap with either PS1 or PS2 immunoreactivity. The ligand Jagged-1 was found sporadically in the neuroepithelial cell layer in cerebral cortex of the earlier stages of development and of the spinal cord during the first trimester while Jagged-2 was not detected. Jagged-1 and Jagged-2 immunoreactivities were not found in the 9-11-week cortex. No co-distribution of Jagged-1 and PS1 or PS2 was found. Delta-1 ligand expression was detected in neuroepithelial cells of the ventricular zone of the cerebral cortex, and also in maturating neurons in the cortical plate and ventral horns of the developing spinal cord. The presence of Notch-1, Delta-1 and Jagged-1 in the neuroepithelium of developing CNS indicates that Notch signaling in proliferating human progenitor cells only involves these two receptor ligands and that cleavage of Notch-1 is mediated both by PS1 and PS2. The strong immunoreactivity of Notch-1, Delta-1 and PS1 in the cortical plate and in maturating neurons of the spinal cord also suggests that these proteins may regulate the maturation processes of post-mitotic neurons. The pronounced PS1 immunoreactivity in neurites in the hindbrain and spinal cord without detectable expression of any Notch receptor or ligand suggests that a possible role for PS1 in neurite growth involves either gamma-secretase-mediated cleavage of other substrates or gamma-secretase-independent mechanisms.

Blotting, Western↗

PubMed2004

Recovery from unilateral neglect after right-hemisphere stroke.

PURPOSE: To show the recovery process for different forms of unilateral neglect (UN)--including personal neglect and neglect of far space--in relationship to impairment, disability, cognition and mood. METHOD: Patients were tested at 2-4 weeks, at 6 months and at 1 year. We used the Behaviour Inattention Test and a test for personal neglect. We also used the NIH Stroke Scale, the Functional Independence Measure (FIM), the Mini-Mental State Evaluation and the Geriatric Depression Scale. RESULTS: Peripersonal neglect diminishes within 6 months, but complete recovery occurred in only 13%. The prognosis for personal neglect and neglect of far space is better, with a recovery ratio at 6 months of 52% and 46%, respective. The correlations between UN and FIM are high. A few patients deteriorate in the absence of recurrent stroke. CONCLUSIONS: For clinical purposes, it is practical to postpone UN evaluation until a couple of weeks after a stroke. Many of the patients who then have UN are likely to retain their UN, although many will improve. Patients with UN should receive special attention in the rehabilitation phase, as well as at discharge. One explanation of the worsening of UN seen in some patients, may be continuing cerebral atherosclerosis.

Activities of Daily Living↗

PubMed2003

Assessing unilateral neglect: shortcomings of standard test methods.

INTRODUCTION: When investigating the incidence of unilateral neglect in a first-ever stroke population, we found that some patients showed clinical signs of neglect, but managed to pass our tests. The purpose of this paper is to describe the nature of such signs, and analyse why test instruments were insufficiently corresponding to those signs. METHOD: One hundred and thirty-one consecutive patients with first-ever stroke in a community-based sample were evaluated for the presence of unilateral neglect. We used a test battery consisting of tests for visuo-spatial neglect, personal neglect, and anosognosia. Twenty cases of neglect were discovered by standard methods. We asked our collaborators at the wards to report any behavioural abnormality reminiscent of neglect present in patients who had normal test results. Such patients were evaluated clinically. RESULTS: Nine cases with neglect-like symptoms were discovered. Our clinical evaluation of the nine patients indicated several possible explanations for their behavioural abnormalities, including motor neglect, neglect for far extrapersonal space, disturbances of proprioception, and spatial disturbances other than neglect. CONCLUSION: Standard neglect tests do not cover all clinical forms of neglect. It is therefore important not to rely completely on test instruments when diagnosing neglect. More versatile test instruments are desired.

Aged↗

PubMed2002

Spontaneous axonal regeneration in rodent spinal cord after ischemic injury.

Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total length of all NF-immunolabeled axons within the lesion cavities was increased 6- to 10-fold at 5, 10, and 15 wk post-lesion compared with 1 wk post-surgery. In ultrastructural studies we found the putatively regenerating axons within the lesion to be associated either with oligodendrocytes or Schwann cells, while other fibers were unmyelinated. Immunohistochemistry demonstrated that some of the regenerated fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a central origin. These findings suggest that there is a considerable amount of spontaneous regeneration after spinal cord lesions in rodents and that the fibers remain several months after injury. The findings of tyrosine hydroxylase- and serotonin-immunoreactivity in the axons suggest that descending central fibers contribute to this endogenous repair of ischemic spinal cord injury.

Animals↗

PubMed2001

Solid human embryonic spinal cord xenografts in acute and chronic spinal cord cavities: a morphological and functional study.

While therapeutic spinal cord grafting procedures are of interest in the chronic spinal cord injury stage, previous experimental grafting studies, including human spinal cord tissue, have mainly focused on the acute stage. Therefore, solid human embryonic spinal cord grafts were implanted in acute or chronic spinal cord aspiration cavities of immunodeficient rats to compare the morphological and locomotor outcome to that of lesion alone cases. Locomotor function was assessed using the Basso, Beattie, and Bresnahan open-field locomotor rating scale up to 6 months, while the morphological evaluation of graft survival, growth, and integration was performed at 6 weeks or 6 months after implantation. Graft survival was 94% in both lesion models, while graft growth was enhanced in the chronic compared to the acute cavity group. Human specific Thy-1 and neurofilament immunoreactive fibers were observed up to 7 mm into host white matter, while aminergic fibers were observed up to 1 mm into the grafts. Abundant calcitonin gene-related peptide immunoreactive fibers in the grafts in the absence both of immunoreactive cell bodies and colocalized human-specific neurofilament immunoreactivity, suggested host fiber ingrowth. At 6 months, the grafted cases presented less central canal deformation and lower glial fibrillary acidic protein immunoreactivity at the host cavity border compared to that of the nongrafted cases. The strong compensatory regain of locomotor function after unilateral spinal cord lesions was not affected by the human spinal cord grafts. In conclusion, solid human embryonic spinal cord tissue transplanted to a cavity in the adult injured spinal cord results in beneficial morphological effects in both the acute and chronic spinal cord lesion.

Animals↗

PubMed2001

Expression of presenilin-1 and Notch-1 receptor in human embryonic CNS.

In vitro studies have shown that the Alzheimer's disease-related presenilin-1 protein can mediate Notch-1 receptor cleavage during signalling. In the present study, we compared the distribution of presenilin-1 and Notch-1 receptor immunoreactivities in human embryonic CNS tissue during the first trimester of development. Our aim was to gain insight into whether these proteins are likely to interact functionally during human fetal brain development. CNS material was obtained from routine abortions, cryosectioned and studied by means of immunohistochemistry with antibodies to presenilin-1 and Notch-1. At very early stages of embryonic development (four to five gestational weeks) intensive presenilin-1 immunoreactivity could be seen predominantly in neurites in the ventral horn of the spinal cord, where it overlapped with 200-kDa neurofilament immunoreactivity. Presenilin-1 immunoreactivity was also seen in neuroblasts of the ventricular zone of the tel- and mesencephalon, as well as of the brainstem. Notch-1 receptor appeared in neuronal and ependymal cells throughout the CNS. Seven- to eight-week CNS tissue showed similar patterns of presenilin-1 and Notch-1 receptor expression in the spinal cord and cerebral cortex as was seen at five weeks. Both proteins were localised in the neuroepithelial cell layer lining the ventricles, as well as in the cortical plate layer, where immunoreactivity was seen in the cell bodies. In addition, presenilin-1 immunoreactivity was seen in thin neurites in the subplate of the developing cortex. At 10 weeks, presenilin-1 immunoreactivity was reduced in the spinal cord. These results show that, although presenilin-1 and Notch-1 receptor are localised to the same differentiating cell populations in the human cerebral cortex, making a direct interaction possible, these proteins are otherwise confined to different neurons or neuronal compartments, suggesting a role for presenilin-1 during early CNS differentiation that does not involve Notch-1 receptor processing. Double staining for presenilin-1 in the endoplasmic reticulum and presenilin-1 in the Golgi showed overlap to some extent in investigated CNS regions, but not in neurites. This suggests that presenilin-1 function during neurogenesis is not exclusively correlated to protein processing within the endoplasmic reticulum and Golgi, but that presenilin-1 may also be involved in other processes, such as axonal and dendritic outgrowth or synaptic formation. In summary, our findings provide supportive evidence that the presenilin-1 protein is involved in the development and maturation of the human fetal CNS. The presence of presenilin-1 immunoreactivity in both the cell bodies and neurites of developing neurons strongly suggests divergent mechanisms of function for presenilin-1 during human brain development. These may include interactions with any of the Notch receptor proteins, as well as Notch-independent mechanisms.

Biomarkers↗

PubMed2001

RANTES promotes growth and survival of human first-trimester forebrain astrocytes.

We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.

Animals↗

PubMed2000

Expression of interleukin-6 in human dorsal root ganglion cells.

The expression of Interleukin-6 (IL-6) was studied in normal dorsal root ganglia (DRG) of juvenile and foetal humans, using immunohistochemistry and in situ hybridization techniques. There was an expression of IL-6-like immunoreactivity in more than 75% out of neuronal cells in the juvenile ganglia with a peripheral localization, and also an expression in the foetal ganglion cells. There was a co-localization of IL-6 with substance P (SP) and calcitonin gene-related peptide (CGRP) in more than 60% of the DRG cells, respectively. By in situ hybridization 0.9% of the cells in the juvenile ganglia and 1.1% of the cells in the foetal ganglia showed a positive signal for IL-6. In addition, expression of IL-6 was found in juvenile medulla spinalis, preferentially in the white matter.

Calcitonin Gene-Related Peptide↗

PubMed2000

Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: similarities and differences compared with rodents.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNAs are expressed in developing and adult rodent tongue and are important for the proper development of lingual gustatory and somatosensory innervation in rodents. Here, we wished to determine whether the findings in rodents apply to humans. By using in situ hybridization histochemistry, distinct, specific, and in some instances overlapping patterns of BDNF and NT-3 mRNA expression were found in the developing and adult human tongue, gustatory papillae, and taste buds. BDNF mRNA was expressed in the superior surface epithelium of the developing fungiform papillae (i.e., developing taste buds), in the epithelium covering the circumvallate papillae, and in the subepithelial mesenchyme. Interestingly, BDNF mRNA was expressed in the lingual epithelium before nerve fibers reached the epithelium, indicating a prespecialization of the gustatory epithelium before the arrival of nerves. In the adult fungiform papillae, BDNF mRNA labeling was found in taste buds and in restricted areas in the non-gustatory lingual epithelium. NT-3 mRNA was found in the developing lingual epithelium and gustatory papillae. NT-3 mRNA labeling was observed in the adult fungiform taste buds, overlapping with BDNF mRNA labeling, in contrast to what was seen in rodents. NT-3 mRNA was additionally found in restricted areas in filiform papillae. Protein gene product 9.5 (PGP) antibodies were used to investigate a possible correlation between lingual innervation and sites of neurotrophin gene activity. Adult human tongue innervation differed from that of rodents, possibly in part due to a different neurotrophin expression pattern in the human tongue. Based on these findings, we suggest that BDNF and NT-3 are important for the initiation and maintenance of the gustatory and somatosensory innervation also in humans. The broader and somewhat overlapping expression patterns of BDNF and NT-3 mRNAs, compared with rodents, suggest additional and possibly somewhat overlapping roles for BDNF and NT-3 in the human tongue and also indicate differences between species. It is important that interspecies differences be taken into consideration.

Adult↗

PubMed2000

Ionotropic glutamate receptor expression in human spinal cord during first trimester development.

Quantitative receptor autoradiography and immunoblotting were used to study the expression and distribution of AMPA, kainate and NMDA receptors in first trimester human spinal cord obtained from elective abortions ranging from 4 to 11.5 weeks of gestational age. Spinal cord tissue sections were processed for receptor autoradiography with the ligands [3H]AMPA, [3H]kainate and [3H]MK-801 and the optical density was measured separately in a dorsal region (alar plate) and ventral region (basal plate) of the autoradiographs. Binding sites for all three ligands were demonstrated already at 4-5.5 weeks of gestation and increased continuously during the first trimester both in the dorsal and ventral regions. [3H]AMPA binding to both high- and low-affinity sites increased from undetectable levels to about 35 and 400 fmol/mg tissue, respectively, during this period. A temporal difference in the distribution of [3H]AMPA binding sites was observed. The early homogeneous pattern of [3H]AMPA binding in both alar and basal plates had changed to a heterogeneous pattern at 11 weeks of gestation with the highest density of [3H]AMPA binding sites in the superficial layers of the immature dorsal horn. [3H]kainate and [3H]MK-801 binding sites were densely and homogeneously distributed already at 4 weeks, and steadily increased six- and two-fold, respectively, to about 100 fmol/mg tissue at 11.5 weeks of gestation. Immunoreactive bands corresponding to the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D were demonstrated by immunoblotting at the earliest between 4.5 and 7 weeks and increasing concentrations were seen up to 11 weeks of gestation. These results suggest that AMPA, kainate and NMDA receptors are expressed in the human spinal cord early in embryogenesis.

Autoradiography↗

PubMed2000

Functional connections are established in the deafferented rat spinal cord by peripherally transplanted human embryonic sensory neurons.

Functionally useful repair of the mature spinal cord following injury requires axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryonic dorsal root ganglion cells grow for long distances in adult host rat dorsal roots, traverse the interface between the peripheral and central nervous system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal cord. Dorsal root ganglia from human embryonic donors were transplanted in place of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human fibres labelled with a human-specific axon marker were distributed in superficial as well as deep laminae of the recipient rat spinal cord. About 36% of the grafted neurons were double labelled following injections of the fluorescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lumbar spinal cord, indicating that some of the grafted neurons had grown processes into the spinal cord as well as towards the denervated peripheral targets. Electrophysiological recordings demonstrated that the transplanted human dorsal roots conducted impulses that evoked postsynaptic activity in dorsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing human sensory nerve fibres which enter the adult deafferentated rat spinal cord become anatomically and physiologically integrated into functional spinal circuits.

Action Potentials↗

PubMed1999

In vitro expansion of a multipotent population of human neural progenitor cells.

The isolation and expansion of human neural progenitor cells have important potential clinical applications, because these cells may be used as graft material in cell therapies to regenerate tissue and/or function in patients with central nervous system (CNS) disorders. This paper describes a continuously dividing multipotent population of progenitor cells in the human embryonic forebrain that can be propagated in vitro. These cells can be maintained and expanded using a serum-free defined medium containing basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), and epidermal growth factor (EGF). Using these three factors, the cell cultures expand and remain multipotent for at least 1 year in vitro. This period of expansion results in a 10(7)-fold increase of this heterogeneous population of cells. Upon differentiation, they form neurons, astrocytes, and oligodendrocytes, the three main phenotypes in the CNS. Moreover, GABA-immunoreactive and tyrosine hydroxylase-immunoreactive neurons can be identified. These results demonstrate the feasibility of long-term in vitro expansion of human neural progenitor cells. The advantages of such a population of neural precursors for allogeneic transplantation include the ability to provide an expandable, well-characterized, defined cell source which can form specific neuronal or glial subtypes.

Brain↗

PubMed1999

Nerve growth factor-induced stimulation of dorsal root ganglion/spinal cord co-grafts in oculo: enhanced survival and growth of CGRP-immunoreactive sensory neurons.

Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted beside the spinal cord graft. Nerve growth factor or vehicle was injected weekly for 4 weeks into the anterior eye chamber. Co-grafts were examined weekly and, at 6 weeks, processed for calcitonin gene-related peptide (CGRP) immunofluorescence. No differences in overall size were determined for the grafts. Co-grafts treated with nerve growth factor contained many more CGRP neurons (19.4 cells/20 microm) that were significantly larger (mean 764 microm2) than neurons from control co-grafts (8.6 cells/20 microm; mean 373 microm2). In co-grafts treated with nerve growth factor, CGRP-immunoreactive fibers were extensive in the dorsal root ganglion, adjacent iris, and spinal cord compared to control co-grafts. A few CGRP-positive motoneurons were observed in the spinal cord, but no differences in number or size of motoneurons were found. The current report demonstrates that spinal cord and dorsal root ganglia can be co-grafted in oculo for long periods of time. Many dorsal root ganglion neurons survive and send peripheral processes into the iris and central processes into the spinal cord under the influence of exogenous nerve growth factor. The intraocular graft paradigm can be of use to further examine the role of neurotrophic factors in regulating or modulating dorsal root ganglion and spinal cord neurons.

Analysis of Variance↗

PubMed1999

Spasticity after traumatic spinal cord injury: nature, severity, and location.

OBJECTIVE: To assess spasticity in a prevalence population of persons with traumatic spinal cord injury (SCI), and determine the degree of correspondence between self-reported spasticity and investigator-elicited spasticity using the modified Ashworth scale. DESIGN: Survey of a near total (88%) prevalence population. SETTING: Outpatient clinic of a university hospital. PATIENTS: A total of 354 individuals with SCI. MAIN OUTCOME MEASURES: The survey includes self-reported symptoms, neurologic examination (American Spinal Injury Association [ASIA] classification), physical therapy examination, range of motion (ROM), and complications. RESULTS: Presence of problematic spasticity was significantly correlated with cervical incomplete (ASIA B-D) injury. Reports of beneficial effects of spasticity were significantly less common in women. Self-reported problematic spasticity was significantly correlated with extensor spasticity. Spasticity was elicitable by movement provocation in 60% of the patients reporting spasticity. Significant correlations were found between elicitable spasticity and limited ROM. CONCLUSION: Flexion, extension, and abduction movements performed with the patient placed in a standardized supine test position are suitable both for test of ROM and degree of spasticity. Spasticity was not elicitable by movement provocation on physical examination in 40% of the patients who reported spasticity, thus indicating that the patient's self-report is an important complement to the clinical assessment. A significant association between spasticity and contractures (reduced ROM) was seen.

Activities of Daily Living↗

PubMed1998

Tyrosine kinases are required for IFN-gamma-induced growth of human embryonic forebrain astrocytes.

The cytokine IFN-gamma was shown to regulate growth and differentiation of human embryonic forebrain astrocytes. This work investigated a signalling pathway used by IFN-gamma during the process of growth regulation of human fetal astrocytes obtained from first trimester embryos. IFN-gamma induced significantly higher cell survival compared to that of unexposed cultures, and this survival could be suppressed by incubation with the tyrosine protein kinase (TPK) specific inhibitor tyrphostin A47 at the non-toxic concentration of 10(-6) M. The signal transducer and activator of transcription (STAT)-1 was translocated into the nucleus upon IFN-gamma stimulation, which was also blocked by incubation with A47. Our data demonstrate that TPKs are actively involved in growth regulation of the developing brain astrocytes induced by IFN-gamma.

Astrocytes↗

PubMed1998

Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord.

The development of nicotinic acetylcholine receptors (nAChRs) in brains from human fetuses of 4-12 weeks gestational age was studied. The expression of nAChR subunit mRNAs was analyzed using reverse transcriptase-polymerase chain reaction. Expression of alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3 and beta 4 mRNA were all detected in the prenatal spinal cord, medulla oblongata, pons, cerebellum, mesencephalon, subcortical forebrain and cortex during first trimester development. Relative quantification of mRNA showed that the highest levels for alpha 3, alpha 4 and alpha 7 were expressed in the spinal cord, alpha 5 was most abundant in the cortex and beta 3 was highest in the cerebellum. beta 4 seemed to be equally distributed in all regions whereas beta 2 was high in the cortex and cerebellum. A comparison of expression of nAChR subunit mRNAs in the cortex and cerebellum of prenatal and aged (54-81 years) brain showed that mRNA levels for alpha 4, alpha 5, alpha 7, beta 2 and beta 4 were significantly higher in the prenatal cortex and cerebellum than in aged brain, whereas the level of alpha 3 transcript was similar, and beta 3 significantly higher in aged cortex. Specific binding of [3H]-epibatidine to prenatal brain membranes was detected as early as 4-5 weeks of gestation in the spinal cord, medulla oblongata, pons and subcortical forebrain. A positive correlation between gestational age and [3H]-epibatidine and [3H]-cytisine binding was found in several brain regions. The highest specific binding of [3H]-epibatidine and [3H]-cytisine was detected in the spinal cord, pons and medulla oblongata and the lowest in the cortex. Saturation analysis of [3H]-cytisine binding in both prenatal and aged brain were best fit by a model for a single site, whereas binding data for [3H]-epibatidine revealed two classes of binding sites. The early presence of nAChR proteins and gene transcripts shown in the present study suggests an important role for nAChRs in modulating dendritic outgrowth, establishment of neuronal connections and synaptogenesis during development.

Aged↗

PubMed1998

Human embryonic spinal cord grafts in adult rat spinal cord cavities: survival, growth, and interactions with the host.

The ability of solid pieces of transplanted human embryonic spinal cord to survive, grow, and integrate with adult rat host spinal cord tissue was investigated. Unilateral cavities were surgically created at vertebral level T12-T13 in 10 athymic nude rats and 5 regular Sprague-Dawley rats. Seven of the athymic rats acutely received a human spinal cord graft, while the remaining 8 rats served as controls, with cavities alone. After 6 months the morphological outcome was evaluated with cresyl violet and with immunohistochemistry using antibodies toward human-specific neurofilament (hNF), human-specific Thy-1 (Thy-1), neurofilament, glial fibrillary acidic protein, serotonin (5-HT), and tyrosine hydroxylase (TH). The in situ morphology of the human embryonic spinal cord was also investigated and compared with grafts that were six months older. Solid human embryonic spinal cord grafts showed a 100% survival rate, grew to fill the volume of the cavity in a noninvasive manner, and expressed human specific antigens 6 months postgrafting. Thy-1 immunoreactivity (IR) was demonstrated up to 8 mm rostral to the graft suggestive of graft-derived fiber outgrowth. hNF-IR fibers and 5-HT- and TH-IR fibers traversed the graft-host border for a few hundred micrometers, respectively. Finally, our findings suggest that grafted solid pieces of human embryonic spinal cord minimize cystic deformations seen in the adult rat spinal cord with a unilateral cavity.

Animals↗