Glutamatergic alterations in the cortex of genetic absence epilepsy rats.

BACKGROUND: In absence epilepsy, the neuronal hyper-excitation and hyper-synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an in vivo quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied in vivo glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured. RESULTS: Although extracellular concentrations of GABA and GLU in the cortex and thalamus were not significantly different between GAERS and NEC rats, cortical GLU uptake was significantly decreased in unrestrained awake GAERS. Expression of VGLUT2 and synaptophysin was increased in the cortex of GAERS compared to NEC rats, but no changes were observed in the thalamus. CONCLUSION: The specific decrease in GLU uptake in the cortex of GAERS linked to synaptic changes suggests impairment of the glutamatergic terminal network. These data support the idea that a change in glutamatergic neurotransmission in the cortex could contribute to hyperexcitability in absence epilepsy.

How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes.

The lack of draining lymphatic vessels in the central nervous system (CNS) contributes to the so-called "CNS immune privilege." However, despite such a unique anatomic feature, dendritic cells (DCs) are able to migrate from the CNS to cervical lymph nodes through a yet unknown pathway. In this report, labeled bone marrow-derived myeloid DCs were injected stereotaxically into the cerebrospinal fluid (CSF) or brain parenchyma of normal rats. We found that DCs injected within brain parenchyma migrate little from their site of injection and do not reach cervical lymph nodes. In contrast, intra-CSF-injected DCs either reach cervical lymph nodes or, for a minority of them, infiltrate the subventricular zone, where neural stem cells reside. Surprisingly, DCs that reach cervical lymph nodes preferentially target B-cell follicles rather than T-cell-rich areas. This report sheds a new light on the specific role exerted by CSF-infiltrating DCs in the control of CNS-targeted immune responses.

Expression and localization of reelin in human odontoblasts.

Reelin is a large extracellular matrix (ECM) glycoprotein strongly expressed during embryonic development in the central nervous system and involved in architectonic brain development. It could participate in axon plasticity processes or adhesion-recognition between nerve fibers in adulthood. Previously identified from a subtractive cDNA library of fully differentiated human odontoblasts, reelin might be involved in the relationship between dental nerves and odontoblasts in as so far the latter are in close association with pulpal nerve fibers. Here, we show by in situ hybridization and immunohistochemistry that reelin is specifically expressed by human odontoblasts in vivo and in vitro and that an intense expression of the reelin gene is detected in odontoblasts in comparison with pulpal cells (PC). Co-cultures of rat trigeminal ganglion (TG) and odontoblasts allow to mimic odontoblast innervation and demonstrate that neurites contact these cells with reelin molecules as observed in vivo in human dental pulp. Moreover, by RT-PCR, we show that both reelin receptors (namely apolipoprotein E receptor [ApoER-2], very low density lipoprotein receptor [VLDLR] and cadherin-related neuronal receptor [CNR]) and the cytoplasmic adapter Disabled-1 implicated in the reelin signal transduction, were expressed by trigeminal ganglion. On the basis of these data, we suggest that reelin might be an extracellular matrix molecule involved in the terminal innervation of the dentin-pulp complex, promoting adhesion between dental nerve endings and odontoblasts.

Differential patterns of glial fibrillary acidic protein-immunolabeling in the brain of adult lizards.

The present study describes by means of immunohistochemistry the comparative distribution of glial fibrillary acidic protein (GFAP)-positive cells in the forebrain and midbrain of three species of lizards: Eumeces algeriensis, Scincoidae; Agama impalearis, Agamidae; Tarentola mauritanica, Gekkonidae. In the species studied, the different types and proportions of glial cells expressing GFAP showed considerable variation. These cells include radial glia, oval cells, tanycytes, ependymocytes, glia limitans, and astrocytes. In Eumeces, astrocytes are particularly abundant and their processes form numerous perivascular end-feet; in addition well-differentiated ependymal cells and glia limitans express GFAP. These mature glial features are concordant with the relatively advanced phylogenetic level of Eumeces. In Tarentola, relatively few GFAP-expressing glial cells are observed, consisting mainly of radial glia and tanycytes. These features indicate a relatively immature state of the glial cell populations in this species. In Agama, GFAP-immunostained cells are confined to the periventricular and subpial brain areas; the ventricular lining contains numerous GFAP-immunopositive tanycytes and well-differentiated glia limitans. This pattern indicates that the glial cell profile in Agama exhibits characteristics intermediate between Eumeces and Tarentola, a feature which is discordant with the relatively primitive phylogenetic level of Agamidae compared to Gekkonidae. Together, the results of the present study provide novel data on the characterization of GFAP-expressing cell populations in different species of lizards. We suggest that the different glial patterns observed in the lizard brain correlates with developmental and functional aspects.

Proliferative activity and nestin expression in periventricular cells of the adult rat brain.

Mitotic activity in the forebrain subventricular zone is well documented but only in vitro reports suggest the presence of multi-potent stem cells all along the adult mammalian neuraxis. We demonstrate, following cerebroventricular infusion of labeled nucleotides in rat brain, a mitotic activity in the choroid plexus, the ependymal and subependymal layers of the mid- and hindbrain. This proliferation, which probably enables renewal of these structures, was unaffected by the destruction of their serotonergic innervations. Nestin, a marker of immature neural cells, was observed in some proliferative subependymal cells, some classical ependymocytes and in the specialized ependymocytes of the subcommissural organ, the collicular recess and the tanycytes. These observations indicate the presence of immature proliferative cells in the third and fourth periventricular structures, which may generate neural cells.

Papillary tumor of the pineal region.

Primary papillary tumors of the central nervous system are rare. We have encountered a series of six papillary tumors of the pineal region with distinctive features that appear to represent a clinicopathologic entity. The tumors occurred in four women and two men, ranging in age from 19 to 53 years. Imaging studies showed a large well-circumscribed mass in the pineal region. The tumors were characterized by an epithelial-like growth pattern, in which the vessels were covered by a layer of tumoral cells. In papillary areas, the neoplastic cells were large, columnar or cuboidal, with a clear cytoplasm. Nuclei, round or infolded, were found generally at the basal pole of tumoral cells. Immunohistochemically, the tumor cells showed strong staining for cytokeratin, S-100 protein, neuron-specific enolase, and vimentin but only weak or no staining for epithelial membrane antigen and glial fibrillary acid protein. Ultrastructural examination of two cases revealed abundant rough endoplasmic reticulum with distended cisternae filled with secretory product, microvilli, and perinuclear intermediate filaments. The morphofunctional features of these papillary tumors of the pineal region, remarkably uniform within this series, are similar to those described for ependymal cells of the subcommissural organ, and the papillary tumors of the pineal region may be derived from these specialized ependymocytes.

Decreased expression of glutamate transporters in genetic absence epilepsy rats before seizure occurrence.

In absence epilepsy, epileptogenic processes are suspected of involving an imbalance between GABAergic inhibition and glutamatergic excitation. Here, we describe alteration of the expression of glutamate transporters in rats with genetic absence (the Genetic Absence Epilepsy Rats from Strasbourg: GAERS). In these rats, epileptic discharges, recorded in the thalamo-cortical network, appear around 40 days after birth. In adult rats no alteration of the protein expression of the glutamate transporters was observed. In 30-day-old GAERS protein levels (quantified by western blot) were lower in the cortex by 21% and 35% for the glial transporters GLT1 and GLAST, respectively, and by 32% for the neuronal transporter EAAC1 in the thalamus compared to control rats. In addition, the expression and activity of GLAST were decreased by 50% in newborn GAERS cortical astrocytes grown in primary culture. The lack of modification of the protein levels of glutamatergic transporters in adult epileptic GAERS, in spite of mRNA variations (quantified by RT-PCR), suggests that they are not involved in the pathogeny of spike-and-wave discharges. In contrast, the alteration of glutamate transporter expression, observed before the establishment of epileptic discharges, could reflect an abnormal maturation of the glutamatergic neurone-glia circuitry.