Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Survival of brain anoxia during months of winter dormancy by the Western painted turtle, Chrysemys picta, may rely on inactivation of neuronal ion channels. During 2 h of anoxia, Ca2+ influx via the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor decreases 30-40%, but it is not known if prolonged anoxic dormancy is associated with even more profound downregulation of this important channel. Because ionized Ca2+ in cerebrospinal fluid (CSF) increases five- to sixfold during prolonged anoxia, the potential for uncontrolled Ca2+ influx and neurotoxicity is increased. To study the regulation of NMDA receptor activity, we measured NMDA-mediated changes in intracellular Ca2+ (NMDA-DeltaCa2+) in turtle cerebrocortical sheets with fura 2. Turtles were kept in N2-bubbled aquariums for 2 h to 6 wk at 2-3 degrees C. NMDA-DeltaCa2+ decreased 60 +/- 14% (P < 0.05) after 2 h of anoxia and did not decrease further for 6 wk. Intracellular Ca2+ increased from 135 to 183 nM (P < 0.05) after 3 wk of anoxia and thereafter returned toward preanoxic levels. When NMDA receptor activity was assessed in artificial CSF containing the ions found in anoxic brain CSF (pH 7. 25, 69 mM lactate, 8.4 mM Ca2+, and 5.1 mM Mg2+), NMDA-DeltaCa2+ was twice control initially but was 21% less than in normoxic artificial CSF after the end of 6 wk, suggesting altered sensitivity of the NMDA receptor to ionized Ca2+ during prolonged anoxia. Regulation of NMDA receptor activity in turtle cerebrocortex during 6 wk of anoxia thus results in depression of NMDA receptor Ca2+ flux, despite a sixfold increase in ionized extracellular Ca2+.
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PMID:Reduction of NMDA receptor activity in cerebrocortex of turtles (Chrysemys picta) during 6 wk of anoxia. 968 64

Contrary to Golgi's "reticular" theory of nervous structure, it is clear that the synapse rules over communication among nerve cells. Spreading depression, however, does not follow synaptic pathways. It sweeps across gray matter like a political revolution, ignoring structural boundaries and carefully established regulatory mechanisms. Neurons form alliances with their usually subordinate partners, the astrocytes, to cause a perturbation of function that strains resources necessary for recovery. Innocent bystanders, the blood vessels, are obliged to try to ameliorate the disturbance but may not be able to respond optimally in the chaotic environment. Under extreme circumstances, a purge of some of the instigators may ensue. This anarchic picture of interactions among the elements of nervous tissue does little to rescue the reticular theory that was one of Golgi's most important intellectual offerings. Nevertheless, it reminds us that the behavior of populations of nerve cells need not necessarily be limited by the pathways dictated by synaptic junctions. Spreading depression is a multifactorial phenomenon, in which intense depolarization of neurons and/or astrocytes leads to perturbations that include release of K(+), release of glutamate, increase in intracellular Ca(++), release of ATP and local anoxia, as well as vascular changes. This process plays a role in migraine and contributes to the damage produced by brain anoxia, trauma, stroke, and subarachnoid hemorrhage. It may provide clues to new treatments for the damaged brain.
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PMID:Subverting the hegemony of the synapse: complicity of neurons, astrocytes, and vasculature in spreading depression and pathology of the cerebral cortex. 2088 59