Profound astrogliosis coincident with neuronal cell loss is universally described in human and animal models of temporal lobe epilepsy (TLE). In the kainic acid-induced status epilepticus (SE) model of TLE, astrocytes in the hippocampus become reactive soon after SE and before the onset of spontaneous seizures. To determine if astrocytes in the hippocampus exhibit changes in function soon after SE, we recorded from SR101-labeled astrocytes using the whole-cell patch technique in hippocampal brain slices prepared from control and kainic-acid treated rats. Glutamate transporter-dependent currents were found to have significantly faster decay time kinetics and in addition, dye coupling between astrocytes was substantially increased. Consistent with an increase in dye coupling in reactive astrocytes, immunoblot experiments demonstrated a significant increase in both glial fibrillary acidic protein (GFAP) and connexin 43, a major gap junction protein expressed by astrocytes. In contrast to what has been observed in resected tissue from patients with refractory epilepsy, changes in potassium currents were not observed shortly after KA-induced SE. While many changes in neuronal function have been identified during the initial period of low seizure probability in this model of TLE, the present study contributes to the growing body of literature suggesting a role for astrocytes in the process of epileptogenesis.
Astrocytes have emerged as active participants of synaptic transmission and are increasingly implicated in neurological disorders including epilepsy. Adult glial fibrillary acidic protein (GFAP)-positive hippocampal astrocytes are not known for ionotropic glutamate receptor expression under basal conditions. Using a chemoconvulsive status epilepticus (SE) model of temporal lobe epilepsy, we show by immunohistochemistry and colocalization analysis that reactive hippocampal astrocytes express kainate receptor (KAR) subunits following SE. In the CA1 region, GluK1, GluK2/3, GluK4, and GluK5 subunit expression was observed in GFAP-positive astrocytes during the seizure free or “latent” period 1 week following SE. At 8 weeks following SE, a time following SE when spontaneous behavioral seizures occur, the GluK1 and GluK5 subunits remained expressed at significant levels. KAR subunit expression was found in astrocytes in the hippocampus and surrounding cortex, but not in GFAP-positive astrocytes of striatum, olfactory bulb, or brainstem. To examine hippocampal KAR expression more broadly, astroglial-enriched tissue fractions were prepared from dissected hippocampi and were found to have greater GluK4 expression following SE than controls. These results demonstrate that astrocytes begin to express KARs following seizure activity and suggest that their expression may contribute to the pathophysiology of epilepsy.
Summary:Purpose: In patients with tuberous sclerosis complex (TSC), a wide range of neurologic abnormalities develop, including mental retardation and seizures. Brains from TSC patients are characterized by the presence of cortical tubers, large dysmorphic neurons, and abnormal cytomegalic cells. Although analysis of human TSC brain samples led to the identification of these abnormal cell types, very little is known about how these cells function. In an effort to model TSC-associated CNS abnormalities (and ultimately to analyze the electrophysiologic properties of abnormal cells), we examined Eker rats carrying a Tsc2 mutation. Anatomic studies, including standard histologic stains and immunocytochemistry, were performed on young Eker rats exposed to a carcinogen in utero or aged untreated Eker rats (18-24 months old).Methods: Pregnant TSC2 +/− females were injected once a day with hydroquinone (HQ), and offspring were killed at postnatal day P14 or P28. Coronal tissue sections throughout the CNS were prepared and stained for cresyl violet. In separate studies, brains of old untreated Eker rats were sectioned for anatomic analysis by using standard immunohistochemical techniques. Results: Tissue sections stained with cresyl violet did not reveal any gross differences between HQ-treated Eker (Tsc2Ek/+ ) rats and siblings (Tsc2 +/+ ). However, two classes of abnormal giant cells were observed in brain sections from untreated aged Eker rats: (a) large dysmorphic pyramid-like cells immunoreactive for NeuN, tuberin, and EAAC-1 in layers IV-VI; and (b) abnormal cytomegalic cells immunoreactive for glial fibrillary acidic protein (GFAP), vimentin, and nestin in deep cortical layers or along the white matter. In addition, large subependymal astrocytomas were observed in four animals.Conclusions: Our data suggest that cortical tuber formation in Eker rats is a rare event and that prenatal exposure to a nongenotoxic carcinogen such as HQ is not sufficient to induce tuber formation. However, with advanced age, an increased likelihood of astrocytoma formation and the emergence of dysmorphic neurons and cytomegalic cells in the Eker rat brain might exist; each of these abnormalities mimics those seen clinically and could contribute to neurologic problems associated with TSC. Further analysis of this rodent model may be warranted.
The genus Asarum (Aristolochiaceae) encompasses approximately 120 species from five sections. Taxonomic controversies concerning the genus Asarum and/or its intrageneric classification remain unresolved. In particular, sect. Heterotropa accounts for a large percentage of the genus (80 of 120 species) and is well diverged in the Sino-Japanese Forest subkingdom. Reconstruction of Heterotropa phylogeny and estimation of its divergence times would provide significant insight into the process of species diversity in the SinoJapanese floristic region. This study encompassed 106 operational taxonomic units (OTUs), and phylogenetic analyses were conducted based on internal transcribed spacer (ITS) and matK sequences. Although the matK sequences provided informative results solely for section Geotaenium, phylogenetic trees based on ITS regions yielded a clear result for several sections. Three sections, Asarum, Geotaenium and Asiasarum, were supported as robust monophyletic groups, whereas Heterotropa had low support. Sect. Hexastylis was revealed to be polyphyletic, suggesting taxonomic reconstruction would be needed. Sect. Heterotropa comprises two clades, which correspond to species distribution ranges: mainland China and the island arc from Taiwan to mainland Japan via the Ryukyu Islands. It is notable that the common ancestry of the latter clade in the eastern Asian islands was highly supported, suggesting that the present species diversity of Heterotropa was initially caused by allopatric range fragmentation in East Asia.
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