Genome comparisons reveal a dominant mechanism of chromosome number reduction in grasses and accelerated genome evolution in Triticeae.

Single-nucleotide polymorphism was used in the construction of an expressed sequence tag map of Aegilops tauschii, the diploid source of the wheat D genome. Comparisons of the map with the rice and sorghum genome sequences revealed 50 inversions and translocations; 2, 8, and 40 were assigned respectively to the rice, sorghum, and Ae. tauschii lineages, showing greatly accelerated genome evolution in the large Triticeae genomes. The reduction of the basic chromosome number from 12 to 7 in the Triticeae has taken place by a process during which an entire chromosome is inserted by its telomeres into a break in the centromeric region of another chromosome. The original centromere-telomere polarity of the chromosome arms is maintained in the new chromosome. An intrachromosomal telomere-telomere fusion resulting in a pericentric translocation of a chromosome segment or an entire arm accompanied or preceded the chromosome insertion in some instances. Insertional dysploidy has been recorded in three grass subfamilies and appears to be the dominant mechanism of basic chromosome number reduction in grasses. A total of 64% and 66% of Ae. tauschii genes were syntenic with sorghum and rice genes, respectively. Synteny was reduced in the vicinity of the termini of modern Ae. tauschii chromosomes but not in the vicinity of the ancient termini embedded in the Ae. tauschii chromosomes, suggesting that the dependence of synteny erosion on gene location along the centromere-telomere axis either evolved recently in the Triticeae phylogenetic lineage or its evolution was recently accelerated.

Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.

PURPOSE: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N-methyl-D-aspartate (NMDA) receptor (NR) 2A/B coassembled with NR1 subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes. METHODS: The histopathological, morphological, and immunocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from subdural grids. The NMDA antibodies identified subunits NR1 (splicing variants 1a, 1b, 2a, and 2b) and NR2A/B. RESULTS: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity. CONCLUSION: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.

NMDAR2 upregulation precedes mossy fiber sprouting in kainate rat hippocampal epilepsy.

Following intrahippocampal (hilar) kainic acid (KA) lesions in rats, NMDAR2A/B receptor proteins are upregulated significantly in the inner molecular layer (IML) of the dentate gyrus by post-injection day 5. By contrast, the aberrant mossy fibers which reinnervate the IML remained in the subgranular zone before sprouting and synapsing in the IML, which occurs at approximately post-KA day 17. For 40 days thereafter, this mossy fiber ingrowth progressed, while the increased NMDAR2A/B (receptors) immunoreactivity remained at the same densities. These results suggest that new NMDAR2A/B proteins in granule cell dendrites are limited to the IML, which is the eventual site for MF hyperinnervation, neosynaptogenesis, and recurrent synaptic hyperexcitability.

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Glutamate receptor mechanisms in human epileptic dysplastic cortex.

Developmental disorders of neuronal migrations in the human brain are referred to as 'cortical dysplasia', and current knowledge of cortical dysplasia is limited to varied pathologic descriptions which lack specific investigations of glutamate receptor mechanisms. In this study, immunocytochemistry was used to study the expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 and AMPA Glu-R2/3 in human brain resected for intractable epilepsy associated with cortical dysplasia. Seventeen patients were studied with batch-matched glutamate subunit reagents on adjacent 30-microm sections. The most striking microscopic abnormalities identified in cresylecht violet stains were cortical dyslaminations, disoriented neurons, and unexpectedly, very dark Nissl body staining of those dysplastic neurons. NMDAR2A/B intensely labeled dysplastic neurons, showing staining in both the cell bodies and dendritic profiles. However, non-dysplastic neurons were not immunoreactive to NMDAR2A/B. Dysplastic neurons were also labeled by antibodies selective to NMDAR1. Both dysplastic neurons and non-dysplastic neurons were immunoreactive to AMPA GluR2/3. Our results suggest that the epileptic hyperexcitability of dysplastic cortical regions may result, at least in part, from the heteromeric coassembly and expressions of NMDAR2A/B subunits with selectively expressed NMDAR1 splice variants in dysplastic neurons. AMPA receptors are probably also essential but not sufficient to explain the 'epileptic' properties of these dysplastic neurons. A longer, detailed report of some of these findings have been previously published (Ying et al., 1998. J. Neuropathol. Exp. Neurol. 57, 47-62).