Subgranular Layer Of Dentate Gyrus Research Articles

Morphofunctional changes of the astrocyte in rat hippocampus under different corticosteroid conditions

In the present study, we examined the changes in the morphofunction of astrocytes in rat hippocampus under different circulating corticosteroid conditions by immunohistochemistry analysis of glial fibrillary acidic protein (GFAP) and ultra-high-voltage electron microscopy. Each GFAP-immunoreactive cell showed a hypertrophic appearance with well-developed thicker fibrous processes, and the number and the density of GFAP-immunoreactive cells were increased 4 weeks after adrenalectomy, whereas the changes were restored to the sham-control level with corticosterone replacement. The morphometric changes were observed in particular around the pyramidal neurons of CA1 and in the subgranular layer of dentate gyrus. The quantitative analysis clearly showed a significant increase in the number and the density of GFAP-immunoreactive cells in the adrenalectomy group; following corticosterone replacement, these increases were returned to the sham-control level. These changes were also specifically revealed by stereo-observation with ultra-high-voltage electron microscopy. The astrocyte showed more complicated fine three-dimensional branching after adrenalectomy. These results suggested that both the structure and function of astrocytes were modulated by corticosteroids via glucocorticoid receptor.

P2-470: Survival and differentiation of adult skin-derived neuroprecursors in a rat model of age-related cognitive impairment

mer s disease (AD). Up to now no resolutive pharmacological therapy exists and there are increasing arguments regarding the beneficial effect of natural nutrients, able to slow down the progression of the disease. Some have the ability to induce cell proliferation and/or survival. Adult neurogenesis could be a good therapeutic strategy for cognitive aging and neurodegenerative diseases(AD). The aims of this work has been to study the modulatory effect of *LMN diet (cocoa, nuts and other natural extracts) in adult mouse neurogenic brain areas. Methods: 129SV male mice, were feed during 40 days with a standard Harlan 2014 control diet and the same diet containing 9,27% of *LMN. Animals received BrdU injections. Brains were processed for inmunohistological and immunoblots studies. Results: Histological samples of mice feed with *LMN diet, showed a noticeable increasing number of proliferative cells by BrdU and PCNA staining, in the adult neurogenic areas: subventricular zone (SVZ) and subgranular layer of dentate gyrus (sgDG). Using Dcx and PSA-NCAM, an increasing in the undifferentiating neurons were determined in the granular layer of dentate gyrus and in the rostral migratory stream (RMS). The immature oligodendrocytes (Ng2) and astrocytes (GFAP) were also increasing in these brain areas. All these results were corroborated by Western-Blot analysis. Moreover, the several interneurons subpopulations of the olfactory bulb were changed. Increasing the tyrosine hydroxylase, calretinin and calbindin neuronal subpopulations, and decreasing the parvalbumin interneurons. In the dentate gyrus, the granular layer presented a high cell number when comparing with the control animals. Conclusions: All these findings showed that *LMN diet promotes the neurogenesis in the adult mouse neurogenic niches. The differences between interneurons subpopulations of olfactory bulb suggested that, *LMN diet could modulate differentiation process in the RMS. Therefore, *LMN diet could be a promising nutrient that would contribute to the neural replacement and to re-establish the brain function in order to avoid the cognitive decline, the main hallmark in Alzheimer’s disease. *Patent submitted: Reference ES2281270. Acknowledgements: This work has been financed by the Spanish Ministry of Industry, project INGENIO 2010CENIT ref MET-DEV-FUN (2006-2009).

Inhibition of cyclooxygenase-2 reduces proliferation of endogenous neural progenitors and ameliorates the epileptogenic process

Cyclooxygenase-2 (COX-2), the principal isoenzyme in the brain, modulates inflammation, glutamate-mediated cytotoxicity, and synaptic plasticity. Its major metabolite, PGE2, exerts the action via EP1-4 receptor. Status epilepticus (SE) induces the epileptogenic process through the generation of ectopic hilar granule cells, and COX-2 is upregulated during this period. In this study, we investigated whether celecoxib, a selective COX-2 inhibitor, can prevent the epileptogenic process in the pilocarpine-induced SE. Experimental SE was induced with lithium-pilocarpine injection, and celecoxib (20 mg/kg, p.o.) were treated at 2 hours after SE and afterwards for 7 or 35 days. BrdU was injected for 7 or 14 days after SE. Spontaneous recurrent seizure (SRS) were video-monitored. BrdU immunohistochemistry was used for the spatial and temporal analysis of hippocampal cell proliferation, and double labellings using NeuN, calbindin or GFAP antibodies were performed. For in vitro study, cultured human neural stem cells (NSCs, F3 cell) were treated with celecoxib, PGE2, or EP2 receptor agonist butaprost, and analyzed in means of BrdU / Ki-67 labeling index, cell cycle analysis and MTT assay. Celecoxib treatment reduced neural damage at 7 and 42 days after status epilepticus (esp. CA1, CA3 and Hilar damage) and reduced microglial infiltration after SE. In addition, celcoxib treatment reduced the proliferation of neural progenitors in subgranular layer of dentate gyrus, and reduced BrdU+ /Calbindin+ /NeuN+ cells in hilar areas. No hilar ectopic granule cell can be found in celecoxib-treated group (ectopic granule neurons: 45% of hilar BrdU+ cells in epilepsy-only group vs. 0% in epilepsy-celecoxib group). Most of the BrdU-labeled cells in the hilar area are positive to GFAP. Celecoxib treatment reduced reactive COX-2 expression in the SE-damaged brain, especially in the early period (days 1–7), with a decrease in SRS formation (days 28-42; p<0.05). In vitro analysis showed that celecoxib dose-dependently inhibited proliferation of NSCs with a decrease in BrdU/Ki-67 labeling index and in a proportion of S phase by cell cycle analysis. In contrast, PGE2 or butaprost treatment increases NSCs proliferation. COX-2 inhibition interfered with cell cycle propagation of NSCs. Taken together, we provide evidences that inhibition of COX-2 prevents the epileptogenic process, which might be due to the neuroprotective and anti-inflammatory effects, and suppression of abnormal neural progenitor proliferation.

Cystatin C modulates neurodegeneration and neurogenesis following status epilepticus in mouse

Brain damaging insults cause alterations in neuronal networks that trigger epileptogenesis, and eventually lead to the appearance of spontaneous seizures. The present experiments were designed to study the cellular expression and functions of a cysteine proteinase inhibitor, cystatin C, whose gene expression is previously shown to be upregulated in the rat hippocampus during status epilepticus (SE)-induced epileptogenesis. The present data showed that the expression of cystatin C protein increased in the mouse hippocampus 7 days following SE and localized mainly to astrocytes and microglia. Acute neuronal death in the hippocampus at 24 h after SE was reduced in cystatin C-/- mice. Also, the basal level of neurogenesis in the subgranular layer of dentate gyrus was decreased in cystatin C-/- mice compared to wildtype littermates. Interestingly, migration of newly born neurons within the granule cell layer was attenuated in cystatin C-/- mice. These data demonstrate that cystatin C has a role in neuronal death and neurogenesis during SE-induced network reorganization.

Distribution of nestin immunoreactivity in the normal adult human forebrain

The distribution of nestin immunoreactivity was studied in the whole normal adult human forebrains using new anti-human nestin mouse monoclonal and rabbit polyclonal antiserum. The nestin immunoreactive cells could be divided into three types according to their morphological characteristics. The first type contained neuron-like nestin immunoreactive cells, distributed in CA1–3 of hippocampus, septum, the nucleus of diagonal band, amygdala and basal nucleus of Meynert. The second type contained astrocyte-like cells, distributed in the subependymal zone and subgranular layer of dentate gyrus. The third type of cells had smaller cell bodies and fewer processes, also distributed in the subependymal zone and subgranular layer of dentate gyrus. Double immunohistochemical staining showed that the nestin positive, neuron-like cells in the nucleus of diagonal band and hippocampus also expressed NSE. However, the astrocyte-like nestin immunoreactive cells of the subependymal zone and subgranular layer of dentate gyrus were not double labeled with GFAP. Although some nestin immunoreactive fibers were distributed in the infundibulum, no nestin-immunoreactive cells were detected in the cortex. These data indicate that nestin exist in the adult human brain outside of the subependymal zone and dentate gyrus and also implies that nestin-immunoreactive cells may play a role in the modulation of basal forebrain function.