多巴胺对嗅球神经回路调节作用的研究进展

多巴胺是中枢神经系统内很重要的神经递质,发挥很多生理功能,如认知活动和运动功能的调控。对帕金森病患者早期临床研究表明,脑内多巴胺水平也与嗅觉功能有关。嗅球是嗅觉系统中很重要的组成部分。近年来对多巴胺在嗅球嗅觉信息处理的作用多有研究。文中就多巴胺在嗅球中的分布及其作用进行综述。     

The Projections of Mitral Cells from Small Local Regions of the Olfactory Bulb: An Anterograde Tracing Study Using PHA-L (Phaseolus vulgaris Leucoagglutinin)

Numerous anatomical and electrophysiological studies have demonstrated a lack of simple point-to-point topographical relationships between the olfactory bulb and primary olfactory projection areas. They reveal instead, a complex pattern of divergence and convergence. Furthermore, several authors reported that a single mitral cell could project onto different widely spaced cortical regions of the olfactory cortex. In the present study, we attempted to label the projections of a few mitral cells so close together so that they might be assumed to be connected to the same glomerulus, and to determine if these cells had similar patterns of axonal projections. For this purpose small Phaseolus vulgaris leucoagglutinin (PHA-L) injections were performed in the olfactory bulb of adult rats. We found that labelling two to five mitral cells, lying close together in the mitral cell layer, resulted in well-delineated patches of labelled fibres in the cortex. The number of patches was not related to the number of labelled mitral cells but the fibre density in each patch increased with the number of PHA-L filled somata in the olfactory bulb. We conclude that mitral cells lying close together in the mitral cell layer have similar patterns of axonal projections. Functional implications of such an organization in olfactory coding is discussed.     

Olfactory dysfunction in the APP/PS1 transgenic mouse model of Alzheimer's disease: Morphological evaluations from the nose to the brain

Olfactory dysfunction is among the signs of Alzheimer's disease (AD) and cognitive impairment. It has been demonstrated Aβ was associated with olfactory impairment observed in both transgenic mice and in AD patients. In this study, we evaluated amyloid deposition in the olfactory circuit of APP/PS1 transgenic mouse model of AD, which showed olfactory dysfunction in olfactory behavior tests. We found amyloid depositions were widely distributed in the whole olfactory circuit. Moreover, we think these amyloid depositions contribute to neuronal atrophy, dendritic abnormalities, synapse loss and axonal degeneration. Therefore, there was a correlation between olfactory deficits and amyloid deposition. Our findings provide initial insights into the pathological basis of AD‐related olfactory dysfunction.     

Tyrosine Hydroxylase and DOPA Decarboxylase Activities in the Medial Preoptic Area and Arcuate Nucleus During the Estrous Cycle: Effects of Aging

HPLC and Palkovits' microdissection technique were used to measure activities of two catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and dopa decarboxylase (DD), in the medial preoptic area (MPA) and arcuate nucleus (AN), both of which are involved in LH regulation. The measurements were made during an 8-h period at 1200, 1400, 1600, 1800, and 2000 h on the days of proestrus and diestrus in young (4–5-month-old) rats. Similar measurements were made at 1400, 1600, 1800, and 2000 h in middle-aged (8–10-month-old) proestrous rats and in 18–22-month-old persistently diestrous rats. For each hour (1200, 1400, etc.), five to seven rats were used. In the young proestrous rats, TH activity in the MPA increased progressively to maximum levels at 1800 h, which is approximately the time when the proestrous surge of LH is known to occur. In contrast, in the young diestrous rats, in which serum LH is known to remain stable, TH activity remained unchanged throughout the afternoon. As in the young proestrous rats, in the middle-aged proestrous rats TH activity reached a peak at 1800 h followed by a precipitous decline at 2000 h. As in the young diestrous rats, in the old persistently diestrous rats no changes in TH activity were observed. The profiles of TH activity in the AN of the four groups were essentially similar to those in the MPA. The cyclic changes in TH activity observed in this study provide a basis for the reported cyclic changes in NE activity, which, in turn, are believed to be responsible for cyclic changes in LH release. The marked deficiency and absence of changes in TH activity in the acyclic old animals corresponded to the reported marked decrease and absence of fluctuations in catecholamine activity in old age. A correlation between DD activities and catecholamine activities was not obvious, most probably due to the large number of compounds that are known to be substrates for this enzyme.     

Effect of local 6-OHDA and 5,6-DHT injections into the rat olfactory bulb on neophobia and learned aversion to a novel food

This study investigated the role of the noradrenergic (NA) and the serotoninergic (5-HT) centrifugal fibers on the olfactory bulb (OB). For this purpose, behavioral responses largely depending on olfactory information were measured in rats after discrete bilateral injections into the OB with either 6-hydroxydopamine (6-OHDA) or 5,6-dihydroxytryptamine (5,6-DHT) solutions. The evaluation of the level of endogenous 5-HT in the OB was measured by high performance liquid chromatography. The NA fibers appeared lesioned after the 6-OHDA treatment only, whereas the 5-HT level was significantly reduced in 5,6-DHT treated bulbs only (34% of the control value). The animals were fed on usual stock-diet (S) and had the choice between S and a novel food (V) on neophobia test, and again on the following day after aversive conditioning (0.9 mEq/kg LiCl i.p.). The behavioral results showed that the drug administrations were followed by a significant effect in one case only: the intake of V was significantly enhanced in 6-OHDA treated animals during neophobia test. Thus, neophobia was reduced by 6-OHDA.

The data are interpreted as follows: (1) the lesion of the bulbar NA or 5-HT fibers does not induce total anosmia; and (2) the NA innervation of the OB could play a role in the modulation of behavioral responses to biological odorants.     

Gonadotrophin-releasing hormone and oxytocin secretion from the hypothalamus in vitro during pro-oestrus: the effects of time of day and melatonin

An accurately timed surge of luteinizing hormone (LH), during the second half of the day of pro-oestrus in rats, is a crucial part of the endocrine signal that leads to expulsion of an ovum from an ovarian follicle. LH release is partly controlled by a number of peptides, including gonadotrophin-releasing hormone (GnRH) and oxytocin, which travel from the hypothalamus to the pituitary. The profile of secretion of these peptides is poorly understood. Therefore, the amounts of GnRH and oxytocin that were secreted from hypothalamic explants were determined at several time points during the day of pro-oestrus. Basal secretion of oxytocin from hypothalami taken later in pro-oestrus was greater than from hypothalami taken earlier in the day (p < 0.02). On the other hand, basal secretion of GnRH decreased during the day of pro-oestrus (p < 0.03). The different trends of GnRH and oxytocin secretion reveal that their secretion is regulated by distinct mechanisms. GnRH secretion was higher at midpro-oestrus than late in the day (p < 0.05) consistent with a peak of GnRH having been observed by others in portal blood in the second half of the day of pro-oestrus. Responsiveness of oxytocin to stimulation by K⁺ of the hypothalami declined from the early light hours to the evening dark hours (p < 0.02). Thus, oxytocin modulation might be achieved partly by modification of intracellular processes. Melatonin, secreted during hours of darkness, is frequently involved in modulating time-dependent events in mammals, but its contribution to peptide regulation during the ovulatory cycle is unclear. Melatonin was observed to inhibit basal oxytocin secretion from hypothalami collected during light hours (p < 0.05). The investigation has, therefore, revealed the potential for melatonin to modulate peptide secretion from the hypothalamus during the day of pro-oestrus. We also observed that secretion from the hypothalamus of the two LH-regulating peptides, GnRH and oxytocin, are differently regulated during the day of pro-oestrus.     

Localization of Nitric Oxide Synthase in the Mouse Olfactory and Vomeronasal System: a Histochemical, Immunological and In Situ Hybridization Study

The distribution of nitric oxide synthase (NOS) in the mouse olfactory bulb and olfactory epithelium, including the vomeronasal organ, was studied using an anti-NOS antibody, NADPH diaphorase histochemistry and in situ hybridization with NOS specific antisense oligonucleotide probes. Interneurons containing NOS protein and mRNA, and exhibiting NADPH diaphorase activity were detected in the plexiform layer of the main olfactory bulb and the granule cell layer of main and accessory olfactory bulbs. Periglomerular cells and granule cells in the main olfactory bulb were also NOS positive with diaphorase and immunostaining for NOS. In contrast, no evidence for NOS expression was found either in the main olfactory epithelium or in the vomeronasal organ, in spite of the strong diaphorase staining of the surface of the main olfactory epithelium. Polymerase chain reaction amplification experiments for detection of NOS gene expression further indicated that NOS is expressed in the olfactory bulb but not in either the main olfactory epithelium or vomeronasal organ. Use of an antibody raised against another enzyme, NADPH-P450 oxidoreductase, showed that this protein was strongly expressed in the olfactory epithelium. Activity of this enzyme may account for the diaphorase histochemical staining of the epithelia. An involvement of neuronal nitric oxide synthase in signalling in olfactory receptor neurons is therefore doubtful, although NOS is clearly expressed in neurons in both main and accessory olfactory bulbs.     

Variations of Synaptotagmin I, Synaptotagmin IV, and Synaptophysin mRNA Levels in Rat Hippocampus during the Estrous Cycle

Periodic changes in ovarian steroid levels during fertility cycles affect learning both in humans and in rats in parallel with electrophysiological and morphological fluctuations in selective neuronal populations. In particular, during the estrous cycle of the female rat, hippocampal CA1 region undergoes cyclic modifications in synaptic density. To investigate the molecular mechanisms involved in synaptic remodeling during the estrous cycle, we analyzed the expression of three presynaptic markers, synaptotagmin I, synaptotagmin IV, and synaptophysin, in the female adult rat brain by in situ hybridization. Relative abundance in mRNA for these three markers was quantified at four phases of the estrous cycle: diestrus, proestrus (AM and PM), and estrus. mRNA levels for syt1 exhibited cyclic variations in pyramidal neurons of the CA3 region of hippocampus during the estrous cycle, while mRNA levels for syt4 and SYN were relatively invariant in this or other regions of the hippocampus. Because CA3 pyramidal neurons make synaptic contacts in CA1, modulation of syt1 expression in CA3 may participate in the changes in synaptic density observed in CA1 during the estrous cycle. Furthermore, both syt1 and SYN mRNA varied cyclically in layer II, but not in layer III of entorhinal cortex, while syt4 remained unchanged throughout the cycle. These data suggest that regular variations in steroid hormone levels during fertility cycles may alter the properties of several networks involved in information processing and learning and memory through altered levels of presynaptic proteins.     

Olfactory learning modifies the expression of odour-induced oscillatory responses in the gamma (60-90 Hz) and beta (15-40 Hz) bands in the rat olfactory bulb

This study addressed the question of the possible functional relevance of two different oscillatory activities, beta and gamma (15-40 and 60-90 Hz, respectively) for perception and memory processes in olfactory areas of mammals. Local field potentials were recorded near relay olfactory bulb neurons while rats performed an olfactory discrimination task. Signals reflected the mass activity from this region and characteristics of oscillatory activities were used as an index of local synchrony. Beta and gamma oscillatory activities were quantified by time-frequency methods before during and after odour sampling. In rats early in their training, olfactory sampling was associated with a significant decrease in power in the gamma band in parallel with a weak but significant increase in the beta band (centred on 27 Hz). Several days later, in well-trained rats, the gamma oscillatory depression was significantly enhanced both in duration and amplitude. It appeared within the 500 ms time period preceding odour onset and was further reduced during the odour period. Concurrently the beta oscillatory response (now centred on 24 Hz) during odour sampling was amplified by a twofold factor. The beta band response was modulated according to the chemical nature of the stimuli and rat's behavioural response. This study showed for the first time that odour sampling in behaving animals is associated with a clear shift in the olfactory bulb neuronal activity from a gamma to a beta oscillatory regime. Moreover, the data stress the importance of studying the odour-induced beta activity and its relation to perception and memory.     

Distinct Characteristics of Odor-evoked Calcium and Electrophysiological Signals in Mitral/Tufted Cells in the Mouse Olfactory Bulb

Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca²⁺ signals in genetically-identified neuronal populations. Although fiber photometry is widely used in neuroscience research, the relationship between the recorded Ca²⁺ signals and direct electrophysiological measurements of neural activity remains elusive. Here, we simultaneously recorded odor-evoked Ca²⁺ and electrophysiological signals [single-unit spikes and local field potentials (LFPs)] from mitral/tufted cells in the olfactory bulb of awake, head-fixed mice. Odors evoked responses in all types of signal but the response characteristics (e.g., type of response and time course) differed. The Ca²⁺ signal was correlated most closely with power in the β-band of the LFP. The Ca²⁺ signal performed slightly better at odor classification than high-γ oscillations, worse than single-unit spikes, and similarly to β oscillations. These results provide new information to help researchers select an appropriate method for monitoring neural activity under specific conditions.     

Sex Differences in Function of a Pheromonally Stimulated Pathway: Role of Steroids and the Main Olfactory System

Exposure to the pheromones contained in female hamster vaginal secretions (FHVS) produces stereotypic, sex-specific behaviors in Syrian hamsters. Using Fos as a marker of neuronal stimulation we have found that (1) FHVS stimulates neurons in the posterior subdivision of the medial nucleus of the amygdala (MeP), the posterior medial subdivision of the bed nucleus of the stria terminalis (BNSTpm), and the magnocellular subdivision of the medial preoptic nucleus (MPN mag); (2) this stimulation is mediated by the main olfactory system; (3) stimulation of the MPN mag is regulated by testosterone in males; (4) stimulation of the BNSTpm and MeP is regulated by testosterone in females; and (5) FHVS does not induce Fos production in the MPN mag in females regardless of the hormonal state. These results support the hypothesis that the main olfactory system plays an important role in the regulation of pheromonally driven behaviors, identifies functional sex differences in pathways that regulate these behaviors, and emphasizes the different roles of the BNSTpm, MeP, and MPN mag in the regulation of male copulatory behavior.     

Effect of Experimental Limbic Epilepsy on the Estrus Cycle and Reproductive Success in Rats

Summary: Epilepsy was induced in female rats by the injection of tetanus toxin (5 mouse LD50) unilaterally into the ventral hippocampus under anesthesia. During the 2–4 weeks that the rats exhibited intermittent spontaneous convulsions, daily vaginal smear tests showed that their estrous cycle was interrupted. In control rats such interruption only occurred for just a few days after the operation. Investigation of mating behavior, on the first night of proestrus, which occurred after 7 weeks from the operation, showed that there were fewer mounts, intromissions or ejaculations from the males, which were caged with previously epileptic animals. These females produced slighly smaller litters than their controls and there was a marked failure of their young to thrive in comparison with those of the control females. This failure appeared to be related to relatively high "stress" levels in the general laboratory environment. The impairment of reproductive success only lasted about 3 months after the original induction of epilepsy since subsequent litters to the same animals thrived normally.     

Estrous Cycle Variations in Gonadotropin-Releasing Hormone, Substance P and Beta-Endorphin Contents in the Median Eminence, the Arcuate Nucleus and the Medial Preoptic Nucleus in the Rat: A Detailed Analysis of Proestrus Changes

The concentrations of gonadotropin-releasing hormone, substance P and β-endorphin were measured in the median eminence, the arcuate nucleus and the medial preoptic nucleus of 4-day cycling female rats. Very well marked estrous cycle-related fluctuations were registered for these neuropeptides in these areas. The largest variations in concentrations of peptide levels were observed in the median eminence. Substance P concentration was highest throughout the day of proestrus as compared to the three others days of the cycle. At the time of the preovulatory luteinizing hormone surge, on the afternoon of proestrus, there was a marked increase in gonadotropin-releasing hormone concentration and a marked decrease in β-endorphin concentration.     

Metabotropic glutamate receptor subtypes in axon terminals of projection fibers from the main and accessory olfactory bulbs: A light and electron microscopic immunohistochemical study in the rat

Localization of metabotropic glutamate receptor subtypes, mGluR1, mGluR1α, mGluR2/3, mGluR4a, mGluR5, mGluR7a, mGluR7b, and mGluR8, was examined in some of the target areas of projection fibers from the main and accessory olfactory bulbs (MOB and AOB) by using subtype-specific antibodies. The superficial layer of the olfactory tubercle and layer Ia of the piriform cortex, the target areas of MOB, showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (-LI), and rather weak mGluR2/3-LI. The periamygdaloid cortical region including the target areas of both MOB and AOB showed intense mGluR2/3-LI as well as marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-LI. No significant mGluR1α-, mGluR4a-, or mGluR7b-LI was seen in these regions. After transection of the lateral olfactory tract, mGluR2/3-, mGluR7a-, and mGluR8-LI were reduced markedly in the target regions on the side ipsilateral to the transection; no significant changes were detected in mGluR1- or mGluR5-LI. Double labeling experiments indicated light and electron microscopically colocalization of mGluR7a- and mGluR8-LI in axon terminals on dendritic shafts of presumed interneurons in the superficial layer of the olfactory tubercle and layer Ia of the piriform cortex. Electron microscopically mGluR2/3-LI was seen in preterminal and terminal portions of axons, whereas mGluR7a- and mGluR8-LI were associated with presynaptic membrane specialization. Immunolabeled axon terminals were filled with round synaptic vesicles and constituted asymmetric synapses with dendritic profiles. The results suggest that glutamate release from axon terminals of projection fibers from MOB and AOB is regulated presynaptically and differentially through mGluR2/3, mGluR7a, and/or mGluR8. J. Comp. Neurol. 393:493–504, 1998. © 1998 Wiley-Liss, Inc.     

An experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). I: Olfactory bulb and ventral area

The fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to comprehensively analyze the connections of the olfactory bulbs and the different regions of the ventral (V) area of the telencephalic lobes (subpallium) of the rainbow trout. With this goal, DiI was applied to the different telencephalic nuclei and zones, as well as to the olfactory nerve, the olfactory bulb, the retina, and to several structures in the diencephalon and brainstem of juvenile trout. The olfactory bulbs maintain reciprocal connections with several regions of the telencephalon [ventral nucleus of V (Vv), supracommissural nucleus (Vs), posterior zone of D (Dp), preoptic nucleus], and also project to the diencephalon (posterior tuberal nucleus, posterior hypothalamic lobe). Vv receives afferents from Vs, the dorsal nucleus of V (Vd), the preoptic nucleus, and from several nuclei in the diencephalon and brainstem (suprachiasmatic nucleus, anterior and lateral tuberal nuclei, preglomerular complex, tertiary gustatory nucleus, posterior tubercle, inferior hypothalamic lobes, thalamus, torus semicircularis, secondary gustatory nucleus, locus coeruleus, superior raphe nucleus, central gray, and reticular formation), and projects to dorsal (pallial) regions and most of the nuclei afferent to Vv. The dorsal nucleus of V (Vd) and Vs mainly project to the dorsal area. In an accompanying article (Folgueira et al., 2004), we present the results of application of DiI to dorsal (pallial) telencephalic regions, as well as of several experiments of tracer application to extratelencephalic regions. The results presented here, together with those of the accompanying article, reveal a complex connectional pattern of the rainbow trout ventral telencephalon, most of these connections having not been described previously in salmonids.     

Expression of the tight junction protein ZO-1 in the olfactory system: Presence of ZO-1 on olfactory sensory neurons and glial cells

The olfactory system is a unique part of the central nervous system since it retains neuronal turnover and regenerative capacities in adulthood. Thus it provides an ideal model to study plasticity of membrane moities involved in cell-cell interactions. One structure particularly involved in cell-cell interaction is the tight junction, which establishes polarization of epithelial cells and creates diffusion barriers to paracellular passages. ZO-1 is a phosphoprotein peripherally associated with tight junctions. We have studied expression of ZO-1 protein in the developing and adult olfactory system of the mouse in order to get information about the localization and developmental expression of this tight junction component. ZO-1 expression has also been determined in cell cultures of olfactory bulbs. ZO-1 was present in the olfactory placode prior to formation of tight junctions. ZO-1 was localized in the developing and mature olfactory epithelium at heterotypic contacts between supporting cells and olfactory neurons as well as at homotypic contacts between both these cell types. Confocal microscopy showed quantitative differences in the ZO-1 expression among different olfactory dendrites. In the olfactory nerves ZO-1 immunolabeling was detectable between olfactory ensheathing cells. From the seventh postnatal day ZO-1 immunolabeling was detected at the mitral cell layer of the bulb on cells tentatively identified as oligodendrocytes. Myelinated tracts of the bulb were ZO-1 negative. Cell cultures of olfactory bulbs showed ZO-1 immunoreaction, mostly localized on glial fibrillary acidic protein (GFAP)-positive cells. Our results provide further evidence that ZO-1 serves functions unrelated to the tight junction complex and indicate molecular heterogeneity of these cell-cell contacts.     

An Investigation of the Effect of Modifying Stimulation Profile Shape on the Loading Response Phase of Gait,during FES‐Corrected Drop Foot: Stimulation Profile and Loading Response

Drop foot stimulators today operate open loop with a trapezoidal stimulation profile. The traditionally applied profile originated as much from technological constraints as suitability for the physical pathology. It was proposed that by increasing the stimulation intensity during the loading response phase of gait, the ankle angle trajectory would become closer to that of normal gait and a more efficient heel rocker would be introduced. One patient, who used an implanted stimulator, was tested. Various profiles, which provided increased stimulation during loading response, were tried and joint angle trajectories, electromyograms, and footswitches were recorded. Statistical analysis was performed using a one way anova and posthoc Tukey tests. The experiment showed that increasing stimulation intensity during loading response increased the duration of the heel rocker. Statistical analysis revealed that this was significant at p = 0.05 level. Increasing stimulation intensity during loading response prolongs the heel rocker. This is an essential mechanism for advancement over the stance limb and providing shock absorption during weight acceptance, thus, we conclude that this improves the gait pattern of the drop foot sufferer.     

Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein

The regeneration of the olfactory neuroepithelium following olfactory bulbectomy or peripheral deafferentation was studied with mRNA probes and antibodies for B-50/GAP43 and for olfactory marker protein (OMP). Two stages in the regeneration of the olfactory epithelium could be discerned with these reagents. The first stage occurs following either peripheral deafferentation of the olfactory epithelium with Triton X-100 (TX-100) or after bulbectomy and is characterized by the formation of a large population of immature olfactory receptor neurons. These newly formed neurons express B-50/GAP43, a phosphoprotein related to neuronal growth and plasticity. During the second stage of the regeneration process the newly formed olfactory neurons mature, as evidenced by a decrease in their expression of B-50/GAP43 and an increase in the expression of OMP. This stage is only manifested if the developing neurons have access to the target olfactory bulb. Formation of a full complement of OMP-expressing neurons occurs only after peripheral lesion with TX-100. In contrast, following bulbectomy the reconstituted olfactory epithelium lacks its normal target and is compromised in its ability to recover from nerve damage, as evidenced by the presence of a large number of B-50/GAP43-expressing neurons up to 3 months after the lesion and its failure to establish a full complement of OMP-expressing neurons. These results demonstrate that the olfactory epithelium is capable of replacing its sensory neurons independently of the presence of its target, the olfactory bulb. However, the differential patterns of expression of B-50/GAP43 and OMP at long times after peripheral lesion with TX-100 or bulbectomy illustrate the profound effect the olfactory bulb has on neuronal maturation in reconstituted olfactory neuroepithelium.     

Selective retrograde transport of tritiated d-aspartate from the olfactory bulb to the anterior olfactory nucleus, pyriform cortex and nucleus of the lateral olfactory tract in the rat

After an injection of [³H]d-aspartate into the olfactory bulb of the rat, retrogradely labeled cells were detected bilaterally in the anterior olfactory nucleus (AON), and ipsilaterally in the pyriform cortex (PC) and nucleus of the lateral olfactory tract (NLOT). These results suggest a certain selective retrograde transport of this amino acid, and are discussed in relation to transmitter candidates in the olfactory bulb.     

Olfactory ensheathing cell transplantation and inhibition of NogoA, NgR and RhoA expression in the damaged zone to ameliorate spinal cord injury

BACKGROUND:Olfactory ensheathing cell(OEC)transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor(NgR),activates downstream inhibitory signal RhoA, and leads to axonal degeneration.OBJECTIVE: To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi'an Jiaotong University School of Medicine, China.MATERIALS: OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RhoA monoclonal antibodies were utilized for detection.METHODS: A total of 40 adult Sprague Dawley rats were randomly assigned to four groups: normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1 μL OECs suspension(1×108/mL)or equivalent DF12 medium at 1 mm above and below the injury site.MAIN OUTCOME MEASURES: Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores.RESULTS: Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury.Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups(P< 0.01), but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups(P< 0.05).CONCLUSION: OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.