Domoic Acid Induces a Long-Lasting Enhancement of CA1 Field Responses and Impairs Tetanus-Induced Long-term Potentiation in Rat Hippocampal Slices
Autor: | Shenfeng Qiu, John H. Ashe, Margarita C. Currás-Collazo, Azadeh K. Jebelli |
---|---|
Rok vydání: | 2009 |
Předmět: |
Male
Blotting Western Long-Term Potentiation Kainate receptor AMPA receptor In Vitro Techniques Hippocampal formation Toxicology Hippocampus Rats Sprague-Dawley Ca2+/calmodulin-dependent protein kinase Animals Receptors AMPA Phosphorylation Protein kinase A Memory Disorders Kainic Acid Neuronal Plasticity Tetanus Chemistry musculoskeletal neural and ocular physiology Excitatory Postsynaptic Potentials Long-term potentiation Rats Electrophysiology Enzyme Activation nervous system Biochemistry Neuromuscular Depolarizing Agents Synaptic plasticity Biophysics NMDA receptor Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Kinases |
Zdroj: | Toxicological Sciences. 111:140-150 |
ISSN: | 1096-0929 1096-6080 |
Popis: | Domoic acid (DOM) is known to cause hippocampal neuronal damage and produces amnesic effects. We examined synaptic plasticity changes induced by DOM exposure in rat hippocampal CA1 region. Brief bath application of DOM to hippocampal slices produces a chemical form of long-term potentiation (LTP) of CA1 field synaptic potentials. The potentiation cannot be blocked by NMDA receptor antagonist MK-801 but can be blocked by the calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 or cAMP-dependent protein kinase (PKA) inhibitor H-89. DOM-potentiated slices show decreased autophosphorylated CaMKII (p-Thr286), an effect that is also dependent on the activity of CaMKII and PKA. Increased phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 (p-Ser831) was seen in DOM-potentiated slices. Therefore, aberrant regulation of CaMKII and GluR1 phosphorylation occurs after DOM application. In addition, tetanus-induced LTP as well as the increase of phosphorylation of CaMKII (p-Thr286) were reduced in DOM-potentiated slices. Compared with brief exposure, slices recovering from prolonged exposure did not show potentiation or altered levels of CaMKII (p-Thr286) or GluR (p-Ser831). However, decreased phosphorylation of GluR1 at Ser845 was seen. These results describe a new chemical form of LTP and uncover novel molecular changes induced by DOM. The observed impairment of tetanus LTP and misregulation of CaMKII and GluR1 phosphorylation may partially account for DOM neurotoxicity and underlie the molecular basis for DOM-induced memory deficit. |
Databáze: | OpenAIRE |
Externí odkaz: |