Immunoglobulin A:Molecular mechanisms of function and role in immune defence

Our immune system produces more immunoglobulin A (IgA) than all of the other antibody classes combined. Much of this synthesis is directed towards protection of the mucosal surfaces which form a vast and vulnerable interface with the environment. As the predominant immunoglobulin class at these surfaces, IgA is an important first line of defence. In addition, IgA is also a major serum immunoglobulin. Both monomeric IgA in serum and polymeric secretory forms of IgA mediate a wide range of protective functions through interaction with numerous receptors and other mediators. It is telling that in order to gain better opportunities for invasion, certain pathogens have evolved mechanisms to thwart IgA function. An improved understanding of this multifaceted immunoglobulin is likely to inform strategies for improved treatments for infections and other diseases.</p

Blockade of Astrocytic Glutamate Uptake in Rats Induces Signs of Anhedonia and Impaired Spatial Memory

Mood disorders are associated with regional brain abnormalities, including reductions in glial cell and neuron number, glutamatergic irregularities, and differential patterns of brain activation. Because astrocytes are modulators of neuronal activity and are important in trafficking the excitatory neurotransmitter glutamate, it is possible that these pathologies are interrelated and contribute to some of the behavioral signs that characterize depression and related disorders. We tested this hypothesis by determining whether depressive-like signs were induced by blocking central astrocytic glutamate uptake with the astrocytic glutamate transporter (GLT-1) inhibitor, dihydrokainic acid (DHK), in behavioral tests that quantify aspects of mood, including reward and euthymia/dysthymia: intracranial self-stimulation (ICSS) and place conditioning. We found that DHK elevated ICSS thresholds, a depressive-like effect that could reflect reduced sensitivity to reward (anhedonia) or increased aversion (dysphoria). However, DHK treatment did not establish conditioned place aversions, suggesting that this treatment does not induce dysphoria. To identify the brain regions mediating the behavioral effects of DHK, we examined c-Fos expression in areas implicated in motivation and emotion. DHK increased c-Fos expression in many of these regions. The dentate gyrus of the hippocampus was robustly activated, which led us to explore whether DHK alters hippocampal learning. DHK impaired spatial memory in the MWM. These findings identify disruption of astrocyte glutamate uptake as one component of the complex circuits that mediate anhedonia and cognitive impairment, both of which are common symptoms of depression. These finding may have implications for the etiology of depression and other disorders that share the features of anhedonia and cognitive impairment