Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant mossy fiber sprouting and synaptic reorganization are plastic responses in human temporal lobe epilepsy, and in pilocarpine-induced epilepsy in rodents. Although the morphological features of the hippocampal epileptic reaction have been well documented, the molecular mechanisms underlying these structural changes are not understood. The classic cadherins, calcium-dependent cell adhesion molecules, are known to function in development in neurite outgrowth, synapse formation, and stabilization. In pilocarpine-induced status epilepticus, the expression of N-cadherin mRNA was sharply upregulated and reached a maximum level (1- to 2.5-fold) at 1- to 4 weeks postseizure in the granule cell layer and the pyramidal cell layer of CA3. N-cadherin protein was correspondingly increased and became concentrated in the inner molecular layer of the dentate gyrus, consistent with the position of mossy fiber axonal sprouts. Moreover, N-cadherin labeling was punctate; colocalized with definitive synaptic markers, and partially localized on polysialated forms of neural cell adhesion molecule (PSA-NCAM)-positive dendrites of granule cells in the inner molecular layer. Our findings show that N-cadherin is likely to be a key factor in responsive synaptogenesis following status epilepticus, where it functions as a mediator of de novo synapse formation.
 ...
PMID:Neural (N-) cadherin, a synaptic adhesion molecule, is induced in hippocampal mossy fiber axonal sprouts by seizure. 1212 71

The cadherin family consists of several homophilic adhesion molecules that, together with their intracellular binding partners the catenins, are known to mediate axonal navigation, target recognition, and synapse formation during development. Here, we have examined the potential role of these molecules in axonal sprouting induced in the adult brain. Over a period of 3 to 60 days, an episode of pilocarpine-induced status epilepticus (SE) led to sprouting of hippocampal mossy fibers both into the CA3 pyramidal cell layer and the inner molecular layer of the dentate gyrus (DG). We found focal up-regulation of N-cadherin, beta-catenin, and alpha-catenin immunoreactivity within segments of the CA3 pyramidal cell layer with pronounced neuron loss that was associated with the development of mossy fiber sprouting. In contrast, expression of these 3 molecules was unaltered in the DG molecular layer despite mossy fiber sprouting in this area. The levels of E-cadherin immunoreactivity were altered prior to the detection of mossy fiber sprouting, with a general reduction in the neuropil and increased expression in CA1/CA3 pyramidal cell somata. Our results imply that members of the cadherin/catenin families undergo specific spatiotemporal patterns of regulation, which may be important in axon target recognition and synapse formation during lesion-induced sprouting.
 ...
PMID:Differential regulation of cadherins and catenins during axonal reorganization in the adult rat CNS. 1238 56

Pathological conditions affect several stages of neurogenesis in the adult brain, including proliferation, survival, cell fate, migration, and functional integration. Here we explored how a pathological environment modulates the heterogeneous afferent synaptic input that shapes the functional properties of newly formed neurons. We analyzed the expression of adhesion molecules and other synaptic proteins on adult-born hippocampal neurons formed after electrically-induced partial status epilepticus (pSE). New cells were labeled with a GFP-retroviral vector one week after pSE. One and three weeks thereafter, synaptic proteins were present on dendritic spines and shafts, but without differences between pSE and control group. In contrast, at six weeks, we found fewer dendritic spines and decreased expression of the scaffolding protein PSD-95 on spines, without changes in expression of the adhesion molecules N-cadherin or neuroligin-1, primarily located at excitatory synapses. Moreover, we detected an increased expression of the inhibitory scaffolding protein gephyrin in newborn but not mature neurons after SE. However, this increase was not accompanied by a difference in GABA expression, and there was even a region-specific decrease in the adhesion molecule neuroligin-2 expression, both in newborn and mature neurons. Neuroligin-2 clusters co-localized with presynaptic cholecystokinin terminals, which were also reduced. The expression of neuroligin-4 and glycine receptor was unchanged. Increased postsynaptic clustering of gephyrin, without an accompanying increase in GABAergic input or neuroligin-2 and -4 expression, the latter important for clustering of GABA(A) and glycine receptors, respectively, could imply an increased but altered inhibitory connectivity specific for newborn neurons. The changes were transient and expression of both gephyrin and NL-2 was normalized 3 months post-SE. Our findings indicate that seizure-induced brain pathology alters the sub-cellular expression of synaptic adhesion molecules and scaffolding proteins related to particularly inhibitory but also excitatory synapses, which may yield functional consequences for the integration of adult-born neurons.
 ...
PMID:Altered synaptic properties during integration of adult-born hippocampal neurons following a seizure insult. 2253 81