Neuroscience
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Comparative Study
N-methyl-D-aspartate receptors in the amygdala are necessary for the acquisition and expression of conditioned defeat.
Here, we describe a biologically relevant model called conditioned defeat that is used to examine behavioral responses to social defeat in Syrian hamsters. In this model experimental animals that are normally aggressive experience social defeat and consequently display high levels of submissive/defensive behavior even in response to non-threatening conspecifics. N-methyl-D-aspartate (NMDA) receptors within the amygdala play an important role in conditioned fear; therefore, the purpose of this study was to examine whether NMDA receptors within the amygdala are necessary for the acquisition and expression of conditioned defeat. ⋯ Similarly, infusions of AP5 into the amygdala immediately before exposure to a non-aggressive intruder significantly attenuated the display of submissive/defensive behavior. These data demonstrate that NMDA receptors are necessary for both the acquisition and expression of conditioned defeat. We believe that conditioned defeat is a unique and valuable animal model with which to investigate the neurobiology of fear-related changes in social behavior.
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The N-methyl-d-aspartate receptor (NMDAR) has been strongly implicated in mechanisms of persistent pain states. The purpose of the present study was to determine whether the NMDAR NR-1, a key subunit in regulation of NMDAR channel complex is directly contributing to the onset and propagation of peripheral nerve injury-induced allodynia and whether N-methyl-d-aspartate (NMDA) signaling interacts with spinal chemokine (chemotactic cytokines) expression and glial activation. We used genetically engineered male mice that had their normal NR1 gene knocked out and expressed a modified NR1 gene at either normal level (NR1 +/+, wild type) or at a low level (NR1+/-, knock down). ⋯ There were no apparent differences in microglial or astrocytic expression between the wild type and knock down mice. These data provide important insights into the cascade of events involving the dynamic interaction between NMDAR function and spinal chemokine and glial production in neuropathic pain states. The results support the findings that chemokine signaling releases glutamate in the spinal cord.
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For many years, research focus on metallothioneins, small zinc binding proteins found predominantly within astrocytes in the brain, has centred on their ability to indirectly protect neurons from oxygen free radicals and heavy metal-induced neurotoxicity. However, in recent years it has been demonstrated that these proteins have previously unsuspected roles within the cellular response to brain injury. The aim of this commentary is to provide an overview of the exciting recent experimental evidence from several laboratories including our own suggesting a possible extracellular role for these proteins, and to present a hypothetical model explaining the newly identified function of extracellular metallothioneins in CNS injury and repair.
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Aquaporin-4 (AQP4) is the predominant water channel in the neuropil of the central nervous system. It is expressed primarily in astrocytes, but also occurs in ependymocytes and endothelial cells. A striking feature of AQP4 expression is its polarized distribution in brain astrocytes and retinal Muller cells. ⋯ We propose that AQP4 works in concert with Kir4.1 and the electrogenic bicarbonate transporter NBC and that water flux through AQP4 contributes to the activity dependent volume changes of the extracellular space. Such volume changes are important as they affect the extracellular solute concentrations and electrical fields, and hence neuronal excitability. We conclude that AQP4-mediated water flux represents an integral element of brain volume and ion homeostasis.
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Audiogenic seizures are a model of generalized tonic-clonic brainstem-generated seizures. Repeated induction of audiogenic seizures, in audiogenic kindling (AuK) protocols, generates limbic epileptogenic activity. The present work evaluated associations between permanence of AuK-induced limbic epileptogenicity and changes in cell number/gluzinergic terminal reorganization in limbic structures in Wistar audiogenic rats (WARs). ⋯ AmK and AuK-AmK were associated with broader cell loss than AuK. Data indicate that permanent AuK-induced limbic epileptogenicity is mainly associated to gluzinergic terminal reorganization in amygdala but not in the hippocampus and with no hippocampal cell loss. Few AmK-induced seizures are associated to broader and higher cell loss than a higher number of AuK-induced seizures.