Disease relevance of kainic acid

• Although this activation was most prominent at 24 h after KA administration in neurons, Smad2P immunoreactivity gradually increased in astrocytes and microglial cells at 3 and 5 days, consistent with reactive gliosis [1].
• The NMDA receptor-specific antagonist MK-801 completely blocked toxicity of NMDA, and the nonNMDA antagonist CNQX preferentially blocked the toxicity of Quis- and KA-type agonists in the spinal cord [2].
• Kainic acid (KA) induces status epilepticus and delayed neurodegeneration of CA3 hippocampal neurons [3].
• Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult mice induces spontaneous recurrent partial seizures and replicates histopathological changes observed in human mesial temporal lobe epilepsy (MTLE) (Bouilleret V et al., Neuroscience 1999; 89:717-729) [4].
• KA produced the highest number of altered cells in the ganglion cell layer (GCL) and in the inner nuclear layer (INL), with an almost complete depletion of ChAT activity [5].

Psychiatry related information on kainic acid

• In KA-treated rats a decrement of right responses and a prolonged reaction time were observed, with these results more evident in animals treated earlier (10 days) [6].
• This study demonstrates that choline supplementation prior to or following KA-induced status epilepticus can protect rats from memory deficits induced by status epilepticus [7].
• In Alzheimer's disease, there was an expanded distribution of the KA receptor field in the dentate gyrus, indicative of sprouting of the commissural and associational fibers [8].
• Kainic acid (KA) and muscimol were injected into the lateral preoptic area (LPO) of the rat to study their effects on drinking behavior [9].
• A local injection of kainic acid (KA) into the dorsal raphe nucleus (NRD) increased the motor activity and produced head shakes, hind limb abduction, forepaw treading and sniffing [10].

High impact information on kainic acid

• Organotypic hippocampal cultures isolated from p35 transgenics demonstrated lowered caspase activity and decreased apoptosis compared with wild type when exposed to KA [11].
• In vivo injection of KA also produced decreased caspase activity and cell death in p35 transgenics vs. wild type [11].
• The present study tested the effects of EUK-134, a synthetic superoxide dismutase/catalase mimetic, on several indices of oxidative stress and neuropathology produced in the rat limbic system as a result of seizure activity elicited by systemic kainic acid (KA) administration [12].
• Eight weeks after KA treatment Synaptopodin protein expression returned to control levels in dendritic layers of CA3 and in the entire molecular layer of the DG [13].
• Using kainic acid (KA) induced epilepsy in rats, the postictal hippocampal expression of synaptopodin was analyzed by in situ hybridization (ISH) and immunohistochemistry [13].

Chemical compound and disease context of kainic acid

• In the pilocarpine and KA models, doses lower than those used in Wistar rats were able to induce status epilepticus (SE) in PG animals [14].
• Model neurotoxicants, methamphetamine (METH) and kainic acid (KA), which are known to cause selective neurodegeneration of anatomically distinct areas of the brain, were evaluated using an animal model of obesity, the ob/ob mouse [15].
• 1. Guanosine-5'-monophosphate (GMP) was evaluated as a neuroprotective agent against the damage observed in rat hippocampal slices submitted to an in vitro model of ischemia with or without the presence of the ionotropic glutamate receptor agonist, Kainic acid (KA) [16].
• In contrast to KA seizures, BC epilepsy had no effect on taurine [17].
• Intracerebroventricular injection of L-alpha-kainic acid (KA) was performed before the induction of transient forebrain ischemia [18].

Biological context of kainic acid

• The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• At the dosage used, the KA produced a 52% decline in the cell density of the inner nuclear layer (INL), a 37% decline in the retinal ganglion cell layer (RGC), and no significant change in the density of cells in the outer nuclear layer (ONL) [20].
• To determine whether this is a general phenomenon of the developing retina, the neurotoxin kainic acid (KA) was injected intraocularly in midlarval-stage Rana pipiens tadpoles to produce selective lesions of certain retinal cell types [20].
• These results raise the possibility that the phosphorylation of KA receptor/channels in their cellular environment is negatively regulated by KA [21].
• Intracellular recordings from CA3 pyramidal cells in irradiated rats revealed recurrent bursts of action potentials on top of large depolarizing waves after KA application [22].

Anatomical context of kainic acid

• These findings suggest that following a KA-seizure, the intrahippocampal ability to reduce the nitroxide radical is impaired, but the ability is intact in the cerebral cortex [23].
• In the juvenile rat, no significant changes in NF-kappaB binding activity were observed in piriform cortex, hippocampus, and cerebellum after KA injection [24].
• Removal of mossy fiber input can therefore reduce KA induced hyperexcitability of CA3 pyramidal cells, but quantitative factors such as proportional loss of granule and hilar cells may explain the considerable differences found among cells and slices [22].
• The prominent GABA(A)-receptor alpha1 subunit staining of interneurons also disappeared after KA treatment, suggesting acute degeneration of these cells [4].
• When added to retinal cultures, both KA and BBT caused developmental stage- and concentration-dependent degeneration without affecting the number or qualitative properties of photoreceptors [25].

Associations of kainic acid with other chemical compounds

• However, pilocarpine-induced seizures result in a more widespread neuronal death in both WT and D2R -/- brains in comparison to KA [26].
• Furthermore, down-regulation of PKC inhibited the increase in TRE-binding activity by NMDA and KA [27].
• Systemic administration of kainic acid (KA), an analogue of glutamic acid, causes limbic seizures and pathophysiological changes in adult rats that are very similar to human temporal lobe epilepsy [28].
• However, this fraction from microsomes contained levels of the 52,000 Mr PSD protein and binding sites for L-glutamate (L-Glu) and L-aspartate (L-Asp) similar to true synaptic junctions, although the Con A binding glycoproteins and KA binding sites were nearly absent [29].
• The saturation curve for glutamate uptake in slices from KA-seized rats killed 2 hours after the first forelimb clonus was displaced to the left, suggesting a compensatory change for the enhanced excitation [30].

Gene context of kainic acid

• The excitotoxin KA decreased MR mRNA levels in CA1 and CA3, decreased GR mRNA levels in DG, and negated all antagonist-induced increases of ACR mRNAs [31].
• Utrophin knockout mice had a normal hippocampal cytoarchitecture but were more sensitive to KA-induced excitotoxicity, as shown by increased mortality and faster progression of the lesion [32].
• In contrast, the NT-3 concentration was unaltered after KA lesion [33].
• However, we found that Lingo-1 mRNA was strongly up-regulated while NgR mRNA was down-regulated in the dentate gyrus in both the BDNF and the KA experiments [34].
• Here, we tested whether the systemic treatment of mice with kainic acid (KA), an amino acid inducing limbic seizures, could elevate in the brain mRNAs encoding uPA and its specific inhibitor, plasminogen activator inhibitor-1 (PAI-1), a major antifibrinolytic agent [35].

Analytical, diagnostic and therapeutic context of kainic acid

• Kainic acid (KA) microinjected into the RVL unilaterally (n = 6) at a dose producing sustained elevation in AP (5 nmol in 100 nl), elicited changes in rCBF similar to those elicited by electrical stimulation [36].
• One of the earliest changes in gene expression after treatment with KA is the induction of immediate-early genes [28].
• Immunocytochemistry and western blot analysis using an antibody that cross-reacts with all known FRAs showed that a 35-kDa FRA was induced at high levels in both the hippocampus and striatum for up to 1 month by KA [28].
• A semiquantitative PCR analysis showed that delta FosB was induced by KA, but its expression lasted for only 6 h [28].
• Transmission electron microscopy showed the integrity of photoreceptor cells in KA- and BBT-treated cultures [25].

References