Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/-showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/-provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects

Neuroprotective Role for Galanin in Alzheimer’s Disease

Galanin (GAL) and GAL receptors (GALR) are overexpressed in degenerating brain regions associated with cognitive decline in Alzheimer\u27s disease (AD). The functional consequences of GAL plasticity in AD are unclear. GAL inhibits cholinergic transmission in the hippocampus and impairs spatial memory in rodent models, suggesting that GAL overexpression exacerbates cognitive impairment in AD. By contrast, gene expression profiling of individual cholinergic basal forebrain (CBF) neurons aspirated from AD tissue revealed that GAL hyperinnervation positively regulates mRNAs that promote CBF neuronal function and survival. GAL also exerts neuroprotective effects in rodent models of neurotoxicity. These data support the growing concept that GAL overexpression preserves CBF neuron function, which may in turn delay the onset of symptoms of AD. Further elucidation of GAL activity in selectively vulnerable brain regions will help gauge the therapeutic potential of GALR ligands in the treatment of AD

What Has Happened to the U.S. Labor Movement? Union Decline and Renewal

For many years, US trade unions declined in union density, organizing capacity, level of strike activity, and political effectiveness. Labor’s decline is variously attributed to demographic factors, inaction by unions themselves, the state and legal system, globalization, neoliberalism, and the employer offensive that ended a labor-capital accord. The AFL-CIO New Voice leadership elected in 1995, headed by John Sweeney, seeks to reverse these trends and transform the labor movement. Innovative organizing, emphasizing the use of rank-and-file intensive tactics, substantially increases union success; variants include union building, immigrant organizing, feminist approaches, and industry-wide non-National Labor Relations Board (or nonboard) organizing. The labor movement must also deal with participatory management or employee involvement programs, while experimenting with new forms, including occupational unionism, community organizing, and strengthened alliances with other social movements