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PubMed1999

Development of a morphologically-based scoring system for postimplantation New Zealand White rabbit embryos.

Rodent whole-embryo culture (WEC) systems are well-established, as are several corresponding morphological scoring systems. Recently, WEC techniques for rabbits have been developed, creating the need for a morphological evaluation system in this species. Consequently, we developed a gestational-age-based quantitative morphology evaluation system for rabbit embryos. Detailed descriptions of 21 embryonic structures, as collected from gestational day (gd) 9-13 rabbit embryos, formed the basis for this evaluation system. These descriptions were then developed into specific criteria for assigning numerical scores to quantify the degree of development of each embryonic structure. The overall morphologic score was calculated as the average of the individual structure scores. To make the system as informative as possible, the numerical scale of the scoring system was gestationally age-based (i.e., range of potential scores was 9.0-13.0). The scoring system was then applied in the evaluation of New Zealand White (NZW) rabbit embryos explanted on gd 9 and cultured for 48 hr. Embryos grown in vitro developed normally, but at a slightly slower rate in vitro than in vivo, as evidenced by the lower morphology score (10.4 in vitro, 11.0 in vivo) and measures of growth (somite number, total protein, and head length). This work firmly establishes the normal archetype of embryonic development in the gd 9-13 NZW rabbit and provides an important tool for the advancement of mechanistic studies of rabbit embryos developing both in vivo and in vitro.

Allantois↗

PubMed1999

Retinoic acid biosynthetic enzyme ALDH1 localizes in a subset of retinoid-dependent tissues during xenopus development.

Control of retinoic acid synthesis in vertebrate organisms is undoubtedly important for regulating the numerous retinoid signaling events which occur during development. The mechanisms which accomplish this task involve enzymes such as class I aldehyde dehydrogenase (ALDH1), which has recently been found to be conserved from amphibians to mammals and which functions as a retinoic acid biosynthetic enzyme in vivo. Here we have found that Xenopus ALDH1 mRNA and protein is expressed in a subset of retinoid-dependent tissues which develop shortly after neurulation during the tail bud stages. ALDH1 mRNA was first clearly detectable by in situ hybridization in stage 28 tail bud embryos localized in the olfactory placode and pronephros, and at stage 35 mRNA was also detected in the pronephric duct. Antibodies were generated against Xenopus ALDH1, and immunohistochemistry was used to demonstrate that ALDH1 protein accumulates in the olfactory placode, pronephros, and dorsal retina at stage 28, and additionally in the lens placode and pronephric duct at stage 35. Neither ALDH1 mRNA nor protein was detected in the posterior region of Xenopus embryos during the tail bud stages. In contrast to neurula stage embryos in which retinoic acid is distributed in an anteroposterior gradient with the high end posteriorly, we found that tail bud stage embryos have retinoic acid present in significant levels in both the head and trunk regions, but with no detection in the posterior region. These findings are consistent with ALDH1 contributing to retinoic acid synthesis needed for development of certain head structures (olfactory placodes, dorsal retina, lens placode) and certain trunk structures (pronephros and pronephric duct). Dev Dyn 1999;215:264-272.

Aldehyde Dehydrogenase↗

PubMed1996

Immunohistochemical and Ultrastructural characterization of the terminal nerve ganglion cells of the ayu, Plecoglossus altivelis (Salmoniformes, Teleostei).

BACKGROUND: Little is known on the cytological properties of the terminal nerve ganglion (TNG) cells in teleosts (Demski, 1993. Acta Anat., 148:81-95). MATERIALS AND METHODS: To characterize the TNG cells of a salmonoid fish, Plecoglossus altivelis, we adopted immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The majority of the TNG cells formed a compact mass halfway between the olfactory sac and the olfactory bulb, whereas a few cells were scattered in the ventromedial region of the olfactory bulb. The cell had a voluminous perikaryon that was positive to antisera against gonadotropin-releasing hormone (GnRH), molluscan cardioexcitatory tetrapeptide (FM-RFamide), and neuropeptide Y (NPY). Immunostaining of consecutive sections with each antiserum showed the coexistence of these antigens in the same cells and their processes. Most of the processes originating from the cells projected centrally to the basal forebrain, including the optic nerve. With TEM, the cells revealed a peptidergic nature, i.e., the presence of abundant granular endoplasmic reticula and well-developed Golgi bodies in association with vesicles that were 70-100 nm in diameter. Occasionally, the cells adjoined one another directly without the intervention of glial sheets. Synaptic contacts were frequent in the proximal region of the processes, where thin lateral processes of the cells and axon terminals of unknown origin were intermingled with each other. Terminal buttons being engulfed by the soma were commonly seen. CONCLUSIONS: The TNG cells of the salmonoid fish share many cytological characteristics with the cells of the nucleus olfactoretinalis of advanced teleosts such as acanthopterygians.

Animals↗

PubMed1997

Ontogenesis and cytomorphology of the nasal olfactory organs in the Oman shark, Iago omanensis (Triakidae), in the Gulf of Aqaba, Red Sea.

BACKGROUND: Sharks (Selachi) are among the largest predators in deep and shallow seas, feeding on live and dead prey. Olfaction is one of the central senses by which they forage, especially at night and in deep water. The organs responsible for this function are the olfactory rosettes, which are situated in their nares. This study follows the ontogenesis and cytological development of the olfactory rosettes of the Oman shark, Iago omanensis, found in the Gulf of Aqaba, Red Sea, at depths of 150-1500 m. METHODS: The sharks were collected bimonthly by means of a specially designed vertical standing net and sacrificed by an overdose of MS222. The olfactory rosettes were extracted from the adults and embryos, then fixed and prepared for EM and LM studies. RESULTS: Iago is a placental, matrotrophic species with a maximal dimension of 800 mm TL (total length). It reproduces all year round, giving birth to a maximum of four (occasionally five) young of 170-180 mm TL. In newborn and adult fish the nasal olfactory organs are as described for other sharks, composed of olfactory lamellae with secondary folds. The number of lamellae increases during embryogenesis up to a maximum of 28-32 in adults. The primary nasal placodes first appear in larvae of 10-14 mm on the dorso-lateral part of the head and then become gradually displaced to the ventral position, typical for adults. Ontogenesis of the nasal rosettes is characterized by a gradual development of the lamellae and their secondary folds, with a concomitant ripening of the sensory elements (ciliated, microvillar, and rod-like bearing cells), as well as glandular and supporting cells and cells containing kinocilia that agitate the nasal water flow. CONCLUSIONS: The released young possess functional olfactory organs and developed neural transmission across the olfactory bulb and tract, to the olfactory lobes in the brain, enabling them to forage from birth. Presented data show the occurrence in I. omanensis of two types of ciliated and microvillar cells. Ciliated and rod-bearing sensory neurons are described for the first time in sharks.

Animals↗

PubMed1998

Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.

In this study, we tested the hypothesis that chronic administration of phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist, would cause a long-lasting behavioral sensitization associated with neuronal toxicity. Female Sprague-Dawley rats were administered PCP (20 mg/kg, i.p.) once a day for 5 days, withdrawn for 72 hr, placed in locomotor activity chambers, and challenged with 3.2 mg/kg PCP. Following assessment of locomotor activity, the rats were killed and their brains processed for analysis of apoptosis by either electron microscopy or terminal dUTP nick-end labeling (TUNEL). In study I, PCP challenge produced a much more robust and long-lasting increase in locomotor activity in rats chronically treated with PCP than in those chronically treated with saline. In study II, clozapine pretreatment blunted the degree of sensitization caused by PCP. In study I, a marked increase in TUNEL-positive neurons was found in layer II of the olfactory tubercle and piriform cortex of rats chronically treated with PCP. Many of these neurons had crescent-shaped nuclei consistent with apoptotic condensation and margination of nuclear chromatin under the nuclear membrane. Acute PCP had no effect. Electron microscopy revealed that PCP caused nuclear condensation and neuronal degeneration consistent with apoptosis. Cell counts in layer II of the piriform cortex revealed that chronic PCP treatment resulted in the loss of almost 25% of the cells in this region. However, an increase in glial fibrillary acidic protein (GFAP)-positive cells in the molecular layer suggests that this neurotoxicity also may involve necrosis. In study II, the PCP-induced neuronal degeneration was essentially completely abolished by clozapine pretreatment. This pattern of degeneration was found to coincide with the distribution of the mRNA of the NR1 subunit of the NMDA receptor. The relevance of these data to a PCP model of chronic NMDA receptor hypofunction is discussed.

Animals↗

PubMed1999

Extracellular single-unit recordings of piriform cortex neurons in rats: influence of different types of anesthesia and characterization of neurons by pharmacological manipulation of serotonin receptors.

In epilepsy research, there is a growing interest in the role of the piriform cortex (PC) in the development and maintenance of limbic kindling and other types of limbic epileptogenesis leading to complex partial seizures. Neurophysiological studies on PC or amygdala-PC slice preparations from kindled rats showed that kindling of the amygdala induces long-lasting changes in synaptic efficacy in the ipsilateral PC, including spontaneous discharges and enhanced susceptibility of PC neurons to evoked burst responses. These long-lasting electrophysiological changes in the PC during kindling appear to be due, at least in part, to impaired function of gamma-aminobutyric acid (GABA)ergic interneurons. The aim of the present study was to develop an anesthetic protocol allowing electrophysiological single-unit recordings from inhibitory, presumably GABAergic PC interneurons in vivo. In addition to recording of spontaneously active PC neurons, microiontophoretic application of glutamate was used to activate silent neurons. Anesthesia of rats with ketamine/xylazine was not suited for single-unit recordings in the PC because of marked cardiovascular depression. Anesthesia with chloral hydrate allowed recording of spontaneous or glutamate-driven single-unit activity in approximately 40% of all animals. A similar percentage was obtained when recordings were done with the narcotic opioid fentanyl (plus gallamine), after all surgical preparations were performed under anesthesia with repeated administration of the barbiturate methohexital. To avoid brain accumulation of methohexital by repeated applications, we modified the anesthetic protocol in that methohexital was only injected once for initiation of surgical anesthesia, followed by the short-acting anesthetic propofol which does not accumulate upon repeated application. Again, after surgical preparation, electrophysiological recordings were done under fentanyl (plus gallamine). By this procedure, spontaneous or glutamate-driven single-unit activity could be measured in all rats in either layer II or III of the PC. Based on shape and frequency of action potentials, two types of neurons were recorded. The predominant type was similar in its firing characteristics to GABAergic neurons in other brain regions, was mainly located in layer III, and could be suppressed by the serotonin2A receptor antagonist MDL 100,907, suggesting that this type of PC neuron represents inhibitory, putative GABAergic interneurons. This new in vivo preparation may be useful for evaluation of PC neurons in kindled rats.

Action Potentials↗

PubMed1996

Oscillations and gaseous oxides in invertebrate olfaction.

Olfactory systems combine an extraordinary molecular sensitivity with robust synaptic plasticity. Central neuronal circuits that perform pattern recognition in olfaction typically discriminate between hundreds of molecular species and form associations between odor onsets and behavioral contingencies that can last a lifetime. Two design features in the olfactory system of the terrestrial mollusk Limax maximus may be common elements of olfactory systems that display the twin features of broad molecular sensitivity and rapid odor learning: spatially coherent oscillations in the second-order circuitry that receives sensory input; and involvement of the interneuronal messengers nitric oxide (NO) and carbon monoxide (CO) in sensory responses and circuit dynamics of the oscillating olfactory network. The principal odor processing center in Limax, the procerebrum (PC) of the cerebral ganglion, contains on the order of 10(5) local interneurons and receives both direct and processed input from olfactory receptors. Field potential recordings in the PC show an oscillation at approximately 0.7 Hz that is altered by odor input. Optical recordings of voltage changes in local regions of the PC show waves of depolarization that originate at the distal pole and propagate to the base of the PC. Weak odor stimulation transiently switches PC activity from a propagating mode to a spatially uniform mode. The field potential oscillation in the PC lobe depends on intercellular communication via NO, based on opposing effects of reagents that decrease or increase NO levels in the PC. Inhibition of NO synthase slows the field potential oscillation, while application of exogenous NO increases the oscillation frequency. A role for CO in PC dynamics is suggested by experiments in which CO liberation increases the PC oscillation frequency. These design features of the Limax PC lobe odor processing circuitry may relate to synaptic plasticity that subserves both connection of new receptors throughout the life of the slug and its highly developed odor learning ability.

Animals↗

PubMed1996

Olfactory information processing in the brain: encoding chemical and temporal features of odors.

A fundamental problem in studying the neural mechanisms of odor recognition and discrimination in the olfactory system lies in determining the features or "primitives" of an odor stimulus that are analyzed by glomerular circuits at the first level of processing in the brain. Several recent studies support the idea that it is not simply the molecular features of odors that contain important information, but also the intermittent pattern of their presentation to the olfactory epithelium that helps determine the behavioral response to odor.

Animals↗

PubMed1996

Adenovirus-mediated gene transfer in olfactory neurons in vivo.

We used recombinant adenoviruses as a means of expressing exogenous genes in olfactory neurons in vivo. A replication incompetent adenovirus (type 5, Ad5) carrying the reporter gene lacZ, which codes for the enzyme beta-galactosidase (beta-Gal), was applied in solution to the olfactory epithelia of rats. The expression of lacZ was controlled by the cytomegalovirus immediate-early promoter/enhancer. beta-Gal expression was observed 1 day postinfection and was maximal at 3-10 days, although it could be detected for at least 21 days postinfection. Expression patterns were heterogeneous, ranging from a few percent to over 25% of the cells in different regions of both turbinate and septal epithelium. Staining was stronger in the olfactory versus respiratory epithelia. In olfactory epithelium staining was almost entirely restricted to olfactory neurons. beta-Gal staining was also observed in the olfactory axons so that nerve bundles could be traced to their targets in the glomerular layer of the olfactory bulb. Intense staining of some glomeruli was evident as long as 21 days postinfection. There was no evidence of cell loss or tissue damage due to viral infection. These results demonstrate that it is possible to use recombinant Ad5 for expressing foreign genes in olfactory neurons. This technique could be used in olfactory neurons to increase expression levels of olfactory specific genes, including the odor receptor, putative guidance and growth molecules, or elements of the transduction cascade, in order to elucidate their biological functions in vivo.

Adenoviridae↗

PubMed1997

Metamorphic remodeling of the primary olfactory projection in Xenopus: developmental independence of projections from olfactory neuron subclasses.

In adult Xenopus, the nasal cavity is divided into separate middle (MC) and principal (PC) cavities; the former is used to smell water-borne odorants, the latter air-borne odorants. Recent work has shown that olfactory neurons of each cavity express a distinct subclass of odorant receptors. Moreover, MC and PC axons project to distinct regions of the olfactory bulb. To examine the developmental basis for this specificity in the olfactory projection, we extirpated the developing MC from early metamorphic (stage 54-57) tadpoles and raised the animals through metamorphosis. In most lesioned animals, the MC partly regenerated. Compared with the unlesioned side, reduction of the region of the glomerular layer of the olfactory bulb receiving MC afferents ranged from 70% to 95%. PC afferents did not occupy regions of the olfactory bulb deprived of MC afferents. These results support a model in which intrinsic cues in the olfactory bulb control the projection pattern attained by ingrowing olfactory axons.

Animals↗

PubMed1997

Serotonin depletion by 5,7-dihydroxytryptamine alters deutocerebral development in the lobster, Homarus americanus.

The olfactory and accessory lobes constitute prominent histological structures within the larval and mature lobster deutocerebrum, and both are associated with a dense innervation from paired serotonergic nerve cells, the dorsal giant neurons (DGNs). During development, the cell bodies of the DGNs are the first central somata to express serotonin (5-HT), and the onset of their 5-HT immunoreactivity coincides with the beginning of accessory lobe formation. In contrast, the olfactory lobe anlagen emerge much earlier and grow in the apparent absence of serotonin. The role of serotonergic input for the development of these brain structures was investigated in lobster embryos after serotonin had been depleted pharmacologically with the neurotoxin 5,7-dihydroxytryptamine. A approximately 90% reduction of serotonin was confirmed in eggs using high-performance liquid chromatography with electrochemical detection. Morphometric analyses suggested that serotonin depletion dramatically slowed the growth of olfactory and accessory lobes, although glomeruli differentiated at the normal time in both areas. The toxin exhibited a high degree of specificity for serotonergic neurons and associated target regions, and serotonin depletion persisted for at least 2 months following treatment. The goal of future experiments is to determine which of the cell types that innervate the olfactory and accessory lobes are affected by toxin treatment, thereby resulting in the retarded growth of these areas.

5,7-Dihydroxytryptamine↗

PubMed1997

Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica.

Unilateral naris closure in young rodents leads to striking alterations in the development of the ipsilateral olfactory system. One of the most pronounced effects is a 25% reduction in the size of the experimental olfactory bulb, a change that stems in part from decreased cell survival. Since naris occlusion in rodents alters the system more during development than in adulthood, we investigated the consequences of olfactory deprivation in a species that is born in a very immature state, Monodelphis domestica. In this pouchless marsupial, offspring are born after a short 14-day gestation. In the present study, the thymidine analogue bromodeoxyuridine was used to examine early postnatal neurogenesis in the olfactory bulb. Unlike rats and mice, neurogenesis of the main output neurons (the mitral cells) continues into postnatal life. Unilateral naris closure was begun on postnatal day 4 (P4) or P5 in Monodelphis and continued for 30 or 60 days. Laminar volume measurements revealed a significant reduction in the size of the experimental bulb following 60, but not 30, days of early olfactory deprivation. Mitral cell number estimates indicated a significant reduction after both 30 and 60 days of naris closure. The immaturity of Monodelphis offspring may render the population of mitral cells susceptible to the effects of olfactory deprivation. These findings suggest that afferent activity plays a role in the survival of all bulb neurons, irrespective of cell class.

Animals↗

PubMed1998

Glomerulus development in the absence of a set of mitral-like neurons in the insect olfactory lobe.

Mitral cells are the first neurons in the mammalian olfactory bulb to synapse with olfactory receptor axons during glomerulus development, and in an invertebrate, the moth Manduca sexta, mitral-like neurons overlap very early with olfactory receptor axons as they begin to form protoglomeruli. The possibility for early interaction between receptor neurons and mitral-like neurons led us to ask whether such an interaction plays an essential role in glomerulus development. In the current study in the moth, we surgically removed a major class of these mitral-like neurons before glomeruli began to form and asked: (a) Is the formation of the array of olfactory glomeruli triggered by an interaction of the first-arriving receptor axons with the dendrites of mitral-like neurons? (b) At the level of individual glomeruli, must the mitral-like dendrites be in place either to maintain receptor axons in a glomerular arrangement, or to guide later-growing dendrites of other types into the developing glomeruli? Our results indicate that even without the participation of this group of mitral-like neurons, the array of sexually isomorphic ordinary glomeruli forms and the basic substructure of individual glomeruli develops apparently normally. We conclude that the mitral-like neurons in Manduca are not essential for the formation of ordinary olfactory glomeruli during development.

Aging↗

PubMed1999

Development of the labial pit organ glomerulus in the antennal lobe of the moth Manduca sexta: the role of afferent projections in the formation of identifiable olfactory glomeruli.

Iterated neuropil modules called glomeruli are characteristic of primary olfactory centers in both vertebrates and invertebrates. To gain insight into the developmental mechanisms underlying the formation of such structured, organized neuropil, we have examined the development of an identified glomerulus in the olfactory (antennal) lobe of the moth Manduca sexta. The labial pit organ glomerulus (LPOG) receives bilateral sensory projections from the labial pit organs in the labial palps of the mouthparts, while other glomeruli in the antennal lobe receive unilateral projections from the antenna. Here, we chronicle the development of the LPOG under normal and perturbed conditions. Our findings suggest that the sensory axons of the labial pit organ, like those of the antenna, induce and shape growth of interneuronal arborizations, but specific features of interneuronal arborizations such as the relative position of glomerular arborizations within the antennal lobe are independent of both classes of afferent innervation. Labial pit organ axons and antennal axons exhibit a high degree of specificity for their respective target regions, independent of the presence or absence of the other class of afferent axon or the route taken to the antennal lobe. Specification of glomerular position is intrinsic to the antennal lobe rather than a consequence of competition between afferent axons.

Aging↗

PubMed1998

D1 dopamine receptors mediate neuroleptic-induced Fos expression in the islands of Calleja.

Systemic injections of the selective, full, D1 agonists A-77636 and SKF-82958 induced pronounced Fos-like immunoreactivity in the islands of Calleja in the olfactory tubercle of intact rats. Fos expression in this region could also be induced by injections of the D2-like dopamine antagonist raclopride (0.5 mg/kg). Pretreatment with the selective D1 dopamine antagonist SCH-23390 (0.2 mg/kg) completely abolished this response, but was without significant effect on raclopride-induced Fos expression in the dorsolateral region of the striatum. SCH-23390 was also able to prevent the atypical neuroleptic clozapine (30 mg/kg) from inducing Fos expression in the islands of Calleja. These findings demonstrate that stimulation of D1 dopamine receptors plays an essential role in neuroleptic induction of Fos-like immunoreactivity in the islands of Calleja, but not in the dorsal striatum, and thus suggest that different mechanisms underlie neuroleptic stimulation of immediate early gene expression in these two structures.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1998

Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys.

The present study used autoradiography to examine the effects of chronic self-administration of cocaine on the density of dopamine D2 receptors in nonhuman primates. Three rhesus monkeys intravenously self-administered an average of 1.35 mg/kg cocaine per day for 18-22 months until they were euthanized immediately after a self-administration session. Binding site density of the D2 ligand [3H]raclopride (2 nM) was assessed in these monkeys as well as three untreated controls, using quantitative in vitro receptor autoradiography. As compared to untreated controls, D2 binding site density was significantly lower in the animals that self-administered cocaine in all regions of the striatum rostral to the anterior commissure. These regions include the anterior and central regions of the caudate nucleus, putamen, olfactory tubercle, and both the shell and core of the nucleus accumbens. Within the substantia nigra and ventral tegmental area, by contrast, no differences were found in the density of D2 binding sites. These findings suggest a pervasive effect of cocaine on the regulation of D2 receptors in the striatum. The lack of change within the ventral midbrain, however, suggests a differential regulation of D2 receptors in the striatum and ventral midbrain. This study confirms and extends our knowledge of the neurobiological changes in the mesolimbic dopamine system that result from chronic exposure to cocaine.

Animals↗

PubMed2000

Basal telencephalic regions connected with the olfactory bulb in a Madagascan hedgehog tenrec.

In an attempt to gain insight into the organization and evolution of the basal forebrain, the region was analysed cytoarchitecturally, chemoarchitecturally, and hodologically in a lower placental mammal, the lesser hedgehog tenrec. Particular emphasis was laid on the subdivision of the olfactory tubercle, the nuclear complex of the diagonal band, and the cortical amygdala. The proper tubercule and the rostrolateral tubercular seam differed from each other with regard to their immunoreactivity to calbindin and calretinin, as well as their afferents from the piriform cortex. Interestingly, the tubercular seam showed similar properties to the dwarf cell compartment, located immediately adjacent to the islands of Calleja. The most prominent input to the olfactory bulb (OfB) originated from the diagonal nuclear complex. This projection was ipsilateral, whereas the bulbar afferents from the hypothalamus and the mesopontine tegmentum were bilateral. The amygdala projected only sparsely to the OfB, but received a prominent bulbar projection. An exception was the nucleus of the lateral olfactory tract, which was poorly connected with the OfB. Unlike other species with an accessory OfB, the projections from the tenrec's main OfB did not show a topographic organization upon the lateral and medial olfactory amygdala. However, there was an accessory amygdala, which could be differentiated from the lateral nuclei by its intense reaction to NADPh-diaphorase. This reaction was poor in the diagonal nuclear complex as in monkey but unlike in rat. The variability of cell populations and olfactory bulb connections shown here may help to clarify both phylogenetic relationships and the significance of individual basal telencephalic subdivisions.

Amygdala↗

PubMed2000

Widespread expression of rat collapsin response-mediated protein 4 in the telencephalon and other areas of the adult rat central nervous system.

The rat collapsin response-mediated protein 4 (rCRMP-4) is a member of a family of proteins that are involved in axonal growth. It is found transiently in postmitotic neurons, such as those that are generated in the adult hippocampus. The authors used immunocytochemistry to investigate whether areas of the rat central nervous system (CNS) that retain postnatal neurogenesis express this protein. They found pronounced rCRMP-4 immunoreactivity in recently generated cells in the dentate granular layer, the subventricular zone, the olfactory bulbs, and the rostral migratory stream, four areas in which the production or migration of neurons occurs in adulthood. However, rCRMP-4 immunoreactivity also is expressed in many other regions of the rat brain in which there is no record of adult neurogenesis or neuronal migration, e.g., in the olfactory glomeruli and in neurons of the cerebral cortex. In the hypothalamus, intensely rCRMP-4-labeled neurons populated the supraoptic, paraventricular, and periventricular nuclei as well as the median eminence and the arcuate nucleus. Immunoreactivity for rCRMP-4 also was present in certain neurons of the interpeduncular nucleus, median raphe, superior colliculus, and scattered granule cerebellar neurons. Many of these regions are known to display axonal outgrowth and/or synaptic rearrangement in adulthood and to coexpress the polysialylated form of the neural cell adhesion molecule. Thus, the results of this study suggest that rCRMP-4 expression in the CNS is associated with cells that are migrating or are undergoing axonal growth. Nevertheless, small, rCRMP-4-immunoreactive cells were seen throughout the brain. These cells did not express neuronal, astroglial, or microglial markers, although some of them also were immunoreactive for rip antibody, suggesting an oligodendroglial lineage.

Animals↗