Cerebral Commissure Research Articles

In vivo modulation of vincristine-induced neurotoxicity in Lymnaea stagnalis, by the ACTH(4-9) analogue Org 2766.

The use of the cytostatic agent vincristine (VCR) is limited by the occurrence of peripheral neuropathy. This side-effect is probably caused by interference with axonal microtubules. VCR depolymerizes microtubules and reacts with tubulin to form paracrystals. The potential of a neurotrophic ACTH(4-9) analogue, Org 2766, to counteract peripheral neuropathy caused by cytostatic agents is being investigated. In the present ultrastructural study, modulatory effects of Org 2766 on VCR-induced neurotoxicity were studied in vivo in neurons of the pond snail Lymnaea stagnalis, which has been shown previously to be a suitable test system to investigate neurotoxic side-effects of cytostatic agents. 24 h after treatment with VCR (25 microM), 68.4 +/- 34.7 paracrystals were counted per cross-section of the cerebral commissure and the number of microtubules in the axons had been lowered to 46% of the control level. After a survival period of two weeks all paracrystals had disappeared. By that time, no recovery of the axonal microtubular system could be observed. However, post-treatment with Org 2766 (10(-6) M) on day 6 after VCR treatment had induced a significant increase in the number of microtubules (+55%) on day 7. This beneficial effect lasted for the rest of the experimental period (14 days). These results suggest that post-treatment with Org 2766, i.e. after VCR clearance, can induce long-lasting beneficial effects on VCR-induced neurotoxicity in vivo.

Effects of cocaine on the rat cerebral commissure

We investigated the effects of cocaine on the corpus callosum, the nerve fibre bundle that connects the bilateral cerebral hemispheres. Our experiments in rats confirmed that, in the control group, the mid-sagittal area of the corpus callosum in the adult male was significantly larger than this area in the female. Early postnatal exposure to cocaine abolished this sexual dimorphism, that is, cocaine-treated males had a significantly smaller callosal area than the control males. Cocaine induced no significant changes in the weight of the body or brain. There were no significant sex differences in the midline sagittal area of the anterior commissure, and no apparent effects of cocaine exposure were determined in this structure. These findings suggest that early postnatal exposure to cocaine abolishes the sexual differentiation of the corpus callosum in male rats.

Immunocytochemical localization of glutamate-like immunoreactivity within the nervous system of the cestode Mesocestoides corti and the trematode Fasciola hepatica.

The localization and distribution of glutamate-like immunoreactivity (IR) in the nervous system of both the cestode Mesocestoides corti and the trematode Fasciola hepatica has been determined by an indirect immunofluorescent technique, in conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was widespread in the central (CNS) and peripheral (PNS) nervous systems of both species examined. In the CNS, IR was evident in nerve cells and fibres in the cerebral ganglia, the cerebral commissure and the dorsal, ventral and longitudinal nerve cords. In the peripheral nervous system (PNS) of M. corti, IR was apparent in nerve plexuses associated with the subtegmental musculature and the musculature associated with the anteriorly positioned suckers. In F. hepatica, IR was evident in the innervation of both the oral and the ventral suckers. In the reproductive system of F. hepatica, glutamate-IR was observed around the ootype/Mehlis' gland complex.

Met-enkephalin Arg-Phe-immunoreactive neurons in the central nervous system of the pond snail Lymnaea stagnalis.

The distribution of an opioid peptide related to YGGFMRF was determined in the CNS and other organs of the pond snail, Lymnaea stagnalis, by RIA and immunocytochemistry. RIA revealed the highest levels in the CNS (1 pmol/organ) and penis (400 fmol/organ). There were also significant levels in the haemolymph, most of which was not associated with haemocytes (580 fmol/ml). Both serial section and whole-mount immunocytochemistry of the CNS revealed immunoreactive cells in every ganglion with the majority in the cerebral and pedal ganglia. In the pedal ganglia some of the immunoreactive cells were close to the cells of the A-cluster, which are known to respond to opioids, and could innervate them. In the cerebral ganglia the immunoreactive cells included a group of neurosecretory cells, the caudo dorsal cells (CDCs) and the terminals of these cells in the cerebral commissure were also stained. The CDCs secrete peptides into the haemolymph and so could be the source of the YGGFMRF immunoreactivity. Immunoreactivity (including the CDCs) was observed in locations that correspond to those reported for other fragments of proenkephalin, such as Met- and Leu-enkephalin, suggesting that they may share a common precursor, a Lymnaea proenkephalin. A map of the 358 YGGFMRF-immunoreactive cells in the CNS is presented, many of which have not been previously identified.

Atrophy and degeneration of peptidergic neurons and cessation of egg laying in the aging pond snail Lymnaea stagnalis.

The morphology of the neuroendocrine caudodorsal cells (CDCs), which are involved in the regulation of female reproduction in the pond snail Lymnaea stagnalis, was studied in young (200 to 234 days of age) and old (400 to 500 days) animals. Lucifer Yellow fills of ventral CDCs showed that in young animals ventral CDCs branch ipsilaterally as well as contralaterally in the cerebral commissure. In old animals these branches were reduced at different degrees and in some cases even lacking completely, leaving only an axon crossing the commissure. Immunocytochemical stainings with antibodies against CDC peptides (CDCH-I and alpha CDCP) corroborated the finding that ventral CDCs degenerate. Among the other types of CDCs (dorsal, lateral), degeneration was found as well. The immunocytochemical findings showed that in old animals the axon terminals of the CDCs were strongly stained, indicating that they are packed with secretory vesicles containing peptides. It was also found that these darkly stained, peptide-containing axon terminals protruded into the perineurium. These findings suggest that accumulation of peptides in the terminals of the CDCs of old animals may be due to the impaired release. The relationship between atrophy and degeneration of CDCs and cessation of egg-laying activity in Lymnaea is discussed.

Development of the nervous system inDugesia tigrinaduring regeneration after fission and decapitation

Summary In the present study of Dugesia tigrina, the development of the nervous system is followed and compared during regeneration after fission and after decapitation. Immunocytochemistry was used, with antisera raised against the biogenic mine, 5-hydroxyhyptamine (5-HT) and the two neuropeptides, neuropeptide F (NPF), and FMRFamide. The results indicate that two processes are involved in the formation of the new cerebral ganglion. First, new processes sprouting from the original main longitudinal nerve cords bend transversely, indicating the position of the developing horseshoe-shaped anterior cerebral commissure. Then new nerve cells in front of the commissure differentiate from neoblasts and their growth cones fasciculate with the fibres from the old main longitudinal nerve cords. In the cerebral ganglion, 5-HT-IR cells appear before NPF-IR cells, in contrast to the pharynx where NPF-IR cells differentiate before the 5-HT-IR cells. In the peripheral nervous system, NPF-IR fibres and cells appear at a...

Fine structure of the cephalic sensory organ in veliger larvae of Littorina littorea, (L.) (Mesogastropoda, Littorinidae)

The cephalic sensory organ (CSO) in planktonic veliger larvae of Littorina littorea is situated dorsally between the velar lobes at the level of the shell aperture. It consists of ciliated primary sensory cells, adjacent accessory cells and supporting epithelial cells. Cell bodies of the ciliated cells originate in the cerebral commissure and their dendrites pass to the epidermis. The flask-shaped sensory cells are characterized by a deep invaginated lumen with modified cilia arising from the cell surface in the lumen. These cilia are presumed to be non-motile because they lack striated rootlets and show a modified microtubular pattern (6 + 2, 7 + 2 and 8 + 2). The adjacent accessory cells never possess an invaginated lumen; occasionally cilia and branched microvilli arise from the apical surface. These cells may be sensory, but there is no obvious direct connection with the nervous system. The supporting epithelial cells are part of the epidermis and flank the apical necks of the sensory and accessory cells. Morphological evidence suggests that the CSO may function in chemoreception related to substrate selection at settlement, feeding or other behaviour.

Serotonergic Modulation of Swimming Speed in the Pteropod Mollusc Clione Limacina:I. Serotonin Immunoreactivity in the Central Nervous System and Wings

Serotonin-immunoreactive somata in the pteropod mollusc Clione limacina were restricted to the cerebral and pedal ganglia. 10-14 pairs of cells were consistently found in the cerebral ganglia, including one large pair that had soma positions and axon branching patterns reminiscent of those of the metacerebral cells of other molluscs. Two clusters of somata were found on the midline near the cerebral commissure, one on the anterior-lateral margin and one posterior-laterally. A distinct paired cluster of up to nine somata was found on the dorso-lateral margin of the pedal ganglia, near the emergence of the pedal commissure. Up to five of these cells innervated the ipsilateral wing via the wing nerve. Dye-fills of these cells showed that they branch repeatedly in the ipsilateral wing and innervate the swim musculature. Double-labelling experiments indicated that the filled neurons were also serotonin-immunoreactive. Neurobiotin fills that were processed for electron microscopy revealed two types of terminals associated with the swim musculature: direct contacts and reactive terminals adjacent to non-labelled presynaptic terminals. Additional immunoreactive neurons in the pedal ganglia included the asymmetrical heart excitor neuron of the left pedal ganglion and up to nine ventral somata.

Immunocytochemical demonstration of a SALMFamide-like neuropeptide in the nervous system of adult and larval stages of the human blood fluke, Schistosoma mansoni

The localization and distribution of SALMFamide immunoreactivity (IR), SI(GFNSALMFamide), in the nervous system of both the adult and larval stages of the trematode Schistosoma mansoni has been determined by an indirect immunofluorescent technique in conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was widespread in the nervous system of adult male and female S. mansoni. In the central nervous system (CNS), IR was evident in nerve cells and fibres in the anterior ganglia, cerebral commissure and dorsal and ventral nerve cords. In the peripheral nervous system (PNS), IR was apparent in nerve plexuses associated with the subtegmental musculature, oral and ventral suckers, the lining of the gynaecophoric canal, and in fine nerve fibres innervating the dorsal tubercles of the male worm. In the reproductive system of male and female worms, S1-IR was only observed around the ootype/Mehlis' gland complex in the female. Immunostaining was also evident in the nervous system of both miracidium and cercarial larval stages. A post-embedding, IgG-conjugated colloidal gold immunostaining technique was employed to examine the subcellular distribution of SALMFamide-IR in the CNS of S. mansoni. Gold labelling of peptide was localized over dense-cored vesicles within nerve cell bodies and fibres constituting the neuropile of the anterior ganglia, cerebral commissure and nerve cords of the CNS. Antigen pre-absorption studies indicated that the results obtained do suggest S1-like immunostaining and not cross-reactivity with other peptides, in particular FMRFamide.

Principles of human brain organization derived from split-brain studies

Studies of damaged human brains have always intrigued neuroscientists. The rich symptomatology that can result is riveting to all who experience examination of such patients. Yet, one of the concerns of basic scientists is that structure-function correlates are difficult to make in the damaged brain, since the lesions are naturally occurring and usually quite diffuse. In addition to the problem of quantitating the lesion, there has always been concern whether the information gained about the brain in the presence of lesions is all that useful in understanding normal brain mechanisms. Are observed effects due to the damage of specific areas or to distant effects? These and other issues have limited the general acceptance of the findings from clinical studies. One of the immediate appeals of the study of patients with surgical division of the forebrain is that the separate functions of the two cerebral hemispheres can be studied readily in the absence of focal damage. Also, the callosal surgery, while producing damage to the brain, was discrete damage to a fiber system and not to nuclear areas. In 1961, R. W. Sperry and his colleagues commenced a series of studies on patients who had undergone surgical section of the cerebral commissures in an effort to control their otherwise intractable epilepsy (Bogen et al., 1965). Studies continue on the original patients as well as others and still shed light on the nature of both cortical and subcortical neural networks. In what follows, I review some aspects of this work to illustrate how this initial work has progressed from the early sixties until the time of Sperry's death in the spring of 1994. Patients who undergo so-called split-brain surgery all suffer from intractable epilepsy. Prior to their surgery, extensive attempts are made to control their seizures medically. Failure to do so, along with other clinical criteria, finds them candidates for surgical division of the corpus callosum, and in some cases the anterior commissure as well. Although these patients are not normal, the onset of their epilepsy varies and has different etiologies. It has not been possible to correlate any of these variations in their neurologic history with the pattern of results obtained from the cognitive studies. It is known from other data that, in order for there to be significant changes in the normal patterns of cerebral lateralization, a large lesion must occur to one side of the brain in early childhood (Rasmussen and Milner, 1977).

ORG-2766, AN ACTH(4-9)-MSH(4-9) ANALOG, MODULATES VINCRISTINE-INDUCED NEUROTOXICITY IN THE SNAIL LYMNAEA-STAGNALIS

In vincristine (VCR) chemotherapy the dose-limiting factor is neurotoxicity, a side-effect which probably is caused by the action of the drug on axonal microtubules. VCR transforms them into paracrystalline structures. ORG 2766, an ACTH(4-9)/MSH(4-9), analogue, might have protective properties against this toxicity, because of its potency to induce the formation of microtubules. Therefore, the effects were studied of co-treatment with VCR and ORG 2766 on paracrystals and on microtubules in axons of the cerebral commissure (CC) of the snail Lymnaea stagnalis. In vitro experiments were carried out, incubating cerebral ganglia including the CC, for various periods of time (5-25 h) in Ringer's solution, in ORG 2766 (10(-6) M), in VCR (10(-4) M), or in VCR+ORG 2766. Furthermore, the effects of VCR (5 h) were studied in CC, pre- and/or post-treated with ORG 2766 (10 h). In another experiment VCR was used at a concentration at which no paracrystals were formed (2x10(-6) M). In this experiment VCR-treatment (5, 15 h) was compared to pre treatment and pre- and post-treatment with ORG 2766 (10 h). The numbers of microtubules (per mu m(2) axoplasm) and paracrystals (number encountered along perpendicular axes of the CC) were counted and the size of the paracrystals was measured in cross-sections of the CC, using electron microscopy. Irrespective of the type of additional treatment, significant differences were not observed in the numbers of paracrystals (32+/-10) after VCR-treatment for 5 h. Between 5 and 10 h of incubation the number increased (to 55+/-21) and remained approximately at this level. The number of microtubules decreased during the first 5 h of VCR treatment from 128+/-16 (control) to 37+/-10, and decreased further 19+/-5 between 5 and 10 h of incubation. The size of the paracrystals of all groups treated for 5 h with either VCR or VCR+ORG 2766 were similar (x=1.7 mu m(2)) However, the paracrystals were significantly larger in all groups co-treated for longer periods (10, 15 or 20 h) with ORG 2766 (VCR: x=2.3-3.0 mu m(2); VCR+ORG 2766: x=3.0-3.4 mu m(2)). This indicates that after an initial period of formation of paracrystals, tubulin is added to the existing paracrystals. At the low VCR concentration studied no paracrystals were formed. However, the number of microtubules had decreased significantly (from 159+/-10 to 84+/-17 after 15 h treatment). Pre- as well as pre- and post-treatment with ORG 2766 resulted in microtubule numbers which were not different from control values, indicating the positive effect of ORG 2766. In the groups pre- and/or post-treated with the high concentration of ORG 2766 (especially in the pre-treated group), the remaining number of microtubules was higher than in those co-treated with VCR and ORG 2766, but lower than in the controls. Although translation of the present results into clinical terms is difficult, they suggest that pre-and/or post-treatment with ORG 2766 may have a benificial effect on VCR-induced neurotoxicity. This conclusion is based on the observation that when ORG 2766 is given before VCR administration or after VCR clearance, larger numbers of microtubules were found in the nervous tissue than after treatment with VCR alone.

Processing and targeting of a molluscan egg-laying peptide prohormone as revealed by mass spectrometric peptide fingerprinting and peptide sequencing.

The neuroendocrine cerebral caudodorsal cells of Lymnaea stagnalis initiate and coordinate ovulation and egg mass production and associated behaviors through the release of a complex set of peptides that are derived from the caudodorsal cell hormone-I (CDCH-I) precursor. We have previously characterized the CDCH-I peptide. In the present study, we isolated and amino acid sequenced by conventional peptide chemistry five additional peptides, epsilon-peptide, calfluxin, alpha-caudodorsal cell peptide, delta-peptide, and carboxyl-terminally located peptide, from the cerebral commissure, the neurohemal area of the caudodorsal cells. Fingerprinting by matrix-assisted laser desorption mass spectrometry of peptides in the commissure demonstrated the presence of all sequenced peptides and, in addition, could identify two other peptides derived from pro-CDCH-1, the beta 1- and beta 3-peptides. These findings together with previous immunocytochemical studies enabled us to define cleavage sites and major processing events of pro-CDCH-1. Pro-CDCH-1 is initially cleaved in the Golgi apparatus into carboxyl- and amino-terminal parts, each of which is sorted into distinct vesicle classes that traffic to different intracellular sites. As a result, in the commissure, peptides derived from the carboxyl-terminal part, including CDCH-1, are present at a many-fold higher concentration than those derived from the amino-terminal part.

Differential trophic effects of ORG 2766, an ACTH(4–9)/MSH(4–9) analogue, on peptidergic neurons and glial cells in the snail Lymnaea stagnalis

Cerebral ganglia of the pond snail Lymnaea stagnalis were incubated in vitro in 10 −6 M ORG 2766 for 10 and 20 h, with or without regular refreshment of the medium. Quantitative ultrastructural study of cross sections of the cerebral commissure showed that the number of microtubules in large axons of all ORG 2766-treated groups had increased after 10 h by approximately 40%. In a separate experiment, central nervous systems were incubated in ORG 2766 for only 15 min and then kept in Ringer's for 9 h and 45 min. Maximal stimulation (40% increase of microtubules) in these specimens was also observed. The results would seem to support the hypothesis that ORG 2766 binds to a receptor and initiates a long-lasting effect. It is argued that ORG 2766 stimulates novel synthesis of tubulin rather than being involved in the assembly of microtubules. Also, glial cells were found to be activated by ORG 2766. This was concluded from the fact that the number of heterochromatin clumps and the size of the clumps in these cells had decreased and the amount of glial tissue surrounding the axons had increased (approximately 50%). In contrast to the activating effects of ORG 2766 on glial tissue, this drug did not affect nucleoli, number, and size of the heterochromatin clumps and the Golgi apparatus in the neuropeptidergic caudodorsal cells. The data indicate that ORG 2766 exerts differential trophic effects.

Studies on the control of spermatogenic DNA synthesis by the mesocerebrum in the snail Helix aspersa.

1. The results obtained after the removal of the supraesophageal part of the circumesophageal neural ring indicate that this part of the brain is involved in the control of spermatogenesis. In hibernating snails, when the supraesophageal ganglia are removed or disconnected from the subesophageal ganglia and from the cerebral sense organs, an increase in the rate of 3H-thymidine incorporation in the male sex cells in the gonad occurs. This suggests that while the supraesophageal ganglia impart an inhibitory influence on the DNA synthesis during spermatogenesis, the subesophageal ganglia stimulate it. 2. The microsurgical removal of different parts of the supraesophageal ganglia suggests that the mesocerebrum plays a major inhibitory role on spermatogonial multiplication. This inhibitory activity originates from groups of mesocerebral neurosecretory cells. These cells have cellular connections to the rest of the periesophageal nerve ring and with the endocrine cells of the dorsal bodies (DB). 3. The extirpartion of islets of neurons located near the cerebral commissure or the section of their axons which form synapse-like-structures with the DB induces an increase in the incorporation of 3H-thymidine by the male sex cells in the gonad. In hibernating adult snails these experiments indicate the inhibitory function of groups of neurons from mesocerebrum on DNA spermatogenic synthesis induced by an increase in temperature (5 to 25 degrees C). In the young snails, this area is the source of growth hormone.

Ultrastructural evidence for the axonal localization of caudodorsal cell hormone mRNA in the central nervous system of the mollusc Lymnaea stagnalis.

The technique of in situ hybridization has been used to evaluate the expression of an ovulation hormone mRNA (caudodorsal cell hormone; CDCH) in the central nervous system (CNS) of the mollusc Lymnaea stagnalis. Hybridization with radioactive as well as with nonradioactive labeled oligonucleotide and plasmid probes revealed a specific labeling on cell bodies of caudodorsal cells (CDCs), which are known to produce CDCH, on the light microscopical level. In addition, specific labeling was observed outside the cell bodies, as far as the cerebral commissure, where CDCH is released in the haemolymph. To investigate whether these signals represent an axonal localization of the CDCH mRNA, we performed in situ hybridization at the electron microscopical (EM) level. The results showed an intraaxonal localization of CDCH mRNA with digoxigenin labeled oligonucleotide and plasmid probes. Gold labeling was observed in secretion granules, and double labeling experiments showed that these granules also contain CDCH. This specific intragranular localization suggest that CDCH mRNA is transported through the axon and released by exocytosis in the haemolymph.

Light and electron microscopic immunocytochemical demonstration of synthesis, storage, and release sites of the neuropeptide calfluxin in Lymnaea stagnalis

The cerebral caudodorsal cells (CDC) of the pulmonate snail Lymnaea stagnalis control egg-laying and associated behaviors. They produce various peptides derived from two precursor molecules, proCDCH-I and II, one of which is calfluxin (CaFl). CaFl is involved in the control of the activity of a female accessory sex gland, the albumen gland. At the light microscope level, using an antibody raised against synthetic CaFl, immunoreactivity was demonstrated in all CDC somata as well as in the neurohemal CDC terminals in the periphery of the cerebral commissure and in the CDC axon collaterals in the inner region of the commissure. A group of small neurons in each cerebral ganglion was also immunopositive. At the ultrastructural level, secretory granules (SG) and large electron-dense granules (LG), formed by the Golgi apparatus and thought to be involved in intracellular degradation of secretory material, were clearly immunolabeled. The density of immunolabeling of LG was 3.3 times greater than that of SG, indicating that CaFl is preferentially packed into LG. In the LG, the density of immunolabeling with anti-αCDCP (αCDCP is also a peptide derived from proCDCH-I and II) was 10 times greater than in SG, suggesting that CaFl and αCDCP are processed and sorted in (quantitatively) different ways. In the neurohemal terminals SG release their CaFl-immunopositive contents into the hemolymph by the process of exocytosis, whereas collaterals release such contents into the intercellular space of the intercerebral commissure. It is proposed that neurohemally released CaFl acts upon the albumen gland, whereas CaFl released from the collaterals may influence the activity of central neurons. CaFl may thus act both as a neurohormone and as a central neurochemical messenger.

Development of serotoninlike immunoreactivity in the embryonic nervous system of the snail Lymnaea stagnalis.

In our initial effort to study the ontogeny of the gastropod nervous system, we used histological techniques to examine the post-embryonic development of cells which exhibit serotoninlike immunoreactivity in Lymnaea (Croll and Chiasson, J. Comp. Neurol. 230:122-142, '89). The present study complements that report by examining the embryonic development of these neurons. The first serotoninlike immunoreactive (SLIR) cells to be detected in the embryos are the paired C4 neurons of the cerebral ganglia. These cells are faintly visible at about 37-38% of embryonic development and have already produced axons which traverse the cerebral commissure. By about 2-3% later the axon tips reach the pedal ganglia and appose the next SLIR cells to appear, the EPe1 neurons. Over the next 30% of development four more pairs of cerebral neurons are added adjacent to the C4 neurons and over ten cells are added to each of the pedal ganglia. At about 70% of development SLIR fibers are first detected in the parietal and visceral ganglia forming the abdominal ring. Around this time the somata of the C1 neurons also first appear in the cerebral ganglia together with their prominent axons projecting to the buccal ganglia. The last 30% of development is marked by a massive addition of SLIR cells (up to 60) in each pedal ganglion. The early appearance of the first SLIR cells suggests that they may be among the first nerve cells to differentiate and that they may play central roles in the formation of the CNS. We hypothesize that most of the animal's neural circuitry is laid down during embryogenesis by a stereotypic ontogenetic program with post-embryonic neurogenesis subserving mostly compensatory and modulatory purposes.

The ACTH/MSH(4–9) analogue ORG 2766 stimulates microtubule formation in axons of central neurons of the snail Lymnaea stagnalis

Central nervous systems of the pond snail Lymnaea stagnalis were incubated in vitro in different concentrations of ORG 2766 ( 10 −9−2.5 × 10 −4 M ) for 10 and 20 h. Quantitative ultrastructural study of cross sections of the cerebral commissure showed that the number of microtubules in large axons had increased after 10 h of incubation by approximately 50% (Experiment 1) and 30% (Experiment 2), respectively. No further increase was observed after 20 h of incubation. (The higher concentrations were studied.) Maximal stimulation was already found at a concentration of 10 −8 M . At a concentration of 10 −9 M control levels were observed. It is concluded that ORG 2766 stimulates microtubule formation already at very low concentrations. It is not clear whether the compound stimulates synthesis of tubulin, induces assembly of microtubules, or causes an increase in stability of microtubules. Nevertheless, ultrastructural data on the morphology of the glial cells indicate that these cells are activated by ORG 2766 treatment, which suggest that ORG 2766 has general trophic effects.

Neurosecretion of the mediodorsal cells of the central nervous system of the snail Helisoma duryi

The neurosecretory mediodorsal cells that produce a putative growth hormone of the snail Helisoma duryi were studied in fast-growing virgin snails and in slow-growing reproducing snails. There are about 60 mediodorsal cells in clusters on each side of the cerebral commissure of the central nervous system, and they contain dense-cored granules which are 100–200 nm in diameter. The cells of virgin snails have dense Golgi bodies, scattered ER cisternae, and few granules, while those of reproducing snails have pale Golgi bodies, stacked ER cisternae, and numerous granules. Thus the mediodorsal cells of the virgin snails appear to be more active synthetically than those of the reproducing snails. The cells near the endocrine dorsal bodies contain many dorsal body precesses in their membrane interdigitations. There are junction-like interactions between some of the interdigitations. Gap junction-like contacts are seen between mediodorsal cells and glial cells. The axon endings of the mediodorsal cells at the neurohemal area in the labial nerve show more release profiles in virgin snails than in reproducing snails. A daily pattern of release has been observed in reproducing snails, and rates of release are higher in the evening than in the morning.

Myelination of the cerebral commissures of the hamster, as revealed by a monoclonal antibody specific for oligodendrocytes

Myelination of the cerebral commissures of the hamster was studied by immunostaining with a monoclonal antibody (Rip) specific for oligodendrocytes. Immunostained, preensheating cells were first observed in the anterior commissure of P6 ( P1 = day of birth). By P8, immunopositive oligodendrocytes and myelinated fibers clustered around some of them were detected within the posterior limb of the anterior commissure, ventrally at the rostral half of the callosum, and in the hippocampal commissure. On P12, all the commissures had myelinated fibers throughout their extent, but the collosum and the hippocampal commissure exhibited higher densities of myelinated fibers rostrally. Between P15 and P22, the pattern of myelination approached that of the adult. In the context of other developmental events, myelination of the corpus callosum and of the anterior commissure is a late event, occuring predominantly after stabilization of axon number, either at the end of the progressive accretion of axons, as in the anterior commissure, or after the selective elimination of callosal projections.