Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.

The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating, a behavior in which central dopamine (DA) has been implicated. Here, we used male prairie voles to examine the effects of drug exposure on pair bonding and related neural circuitry. In our first experiment, amphetamine (AMPH) motivated behavior was examined using a conditioned place preference (CPP) paradigm and was shown to be mediated by activation of D1-like DA receptors. Next, we examined the effects of repeated AMPH exposure on pair bonding. Intact and saline pretreated control males displayed mating-induced partner preferences, whereas males pretreated with AMPH at the doses effective to induce CPP failed to show mating-induced partner preferences. Such AMPH treatment also enhanced D1, but not D2, DA receptor expression in the nucleus accumbens (NAcc). Furthermore, pharmacological blockade of D1-like DA receptors in the NAcc rescued mating-induced partner preferences in AMPH-treated males. Together, our data indicate that repeated AMPH exposure may narrow the behavioral repertoire of male prairie voles via a DA receptor-specific mechanism in the NAcc, resulting in the impairment of pair bond formation.vole | CPP | D1 Receptor I t is widely accepted that motivated and emotional behaviors that promote fitness are regulated by brain reward circuitry including the mesolimbic dopamine (DA) system (1, 2). Although this system is often implicated in food intake and sexual behavior (3, 4), it has also been implicated in other naturally occurring motivated behaviors, such as social play between juveniles and social bonding between parent and offspring (5-9). Often underrepresented in research are the social bonds formed between adult mates, i.e., pair bonds. Recent investigation using a socially monogamous rodent species, the prairie vole (Microtus ochrogaster) (10-12), indicate that a great deal of the neural regulation underlying pair bond formation and maintenance occurs within the nucleus accumbens (NAcc) (13-15)-a mesolimbic brain region critical for mediating motivated behaviors (1, 2, 16).Although motivational circuitry evolved to promote fitness enhancing behavior such as feeding, mating, and social bonding (1, 17), it is vulnerable to artificial usurpation by drugs of abuse (8). For example, administration of psychostimulant drugs of abuse, such as cocaine and amphetamine (AMPH), results in persistent alterations of mesolimbic DA activity (18,19). The intense impact on this circuit by these and other addictive drugs has been suggested to decrease the perceived value of natural incentives (20), including those of a social nature (8). Although it is known that drug addicts show impaired social behavior (21), the neural regulation of interactions between drug experience and social attachment is poorly understood. This is because, in part, such interactions are difficult to model in traditional laboratory rodents that do not exhibit social bonding between adult conspecifics.The neurobiology of su...

Cytokines play crucial roles in orchestrating complex multicellular interactions between pancreatic β cells and immune cells in the development of type 1 diabetes (T1D) and are thus potential immunotherapeutic targets for this disorder. Cytokines that can induce regulatory functions—for example, IL‐10, TGF‐β and IL‐33—are thought to restore immune tolerance and prevent β‐cell damage. By contrast, cytokines such as IL‐6, IL‐17, IL‐21 and TNF, which promote the differentiation and function of diabetogenic immune cells, are thought to lead to T1D onset and progression. However, targeting these dysregulated cytokine networks does not always result in consistent effects because anti‐inflammatory or proinflammatory functions of cytokines, responsible for β‐cell destruction, are context dependent. In this review, we summarise the current knowledge on the involvement of well‐known cytokines in both the initiation and destruction phases of T1D and discuss advances in recently discovered roles of cytokines. Additionally, we emphasise the complexity and implications of cytokine modulation therapy and discuss the ways in which this strategy has been translated into clinical trials.

Edited by Xiao-Fan Wang M2 macrophage polarization is known to underlie kidney fibrosis. We previously reported that most of the members of the Wnt family of signaling proteins are induced in fibrotic kidneys. Dysregulation of the signaling protein Wnt5a is associated with fibrosis, but little is known about the role of Wnt5a in regulating M2 macrophage activation that results in kidney fibrosis. Here, using murine Raw 264.7 cells and bone marrow-derived macrophages, we found that Wnt5a enhanced transforming growth factor ␤1 (TGF␤1)-induced macrophage M2 polarization as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Verteporfin blockade of Yap/Taz inhibited both Wnt5a-and TGF␤1-induced macrophage M2 polarization. In mouse models of kidney fibrosis, shRNA-mediated knockdown of Wnt5a expression diminished kidney fibrosis, macrophage Yap/Taz expression, and M2 polarization. Moreover, genetic ablation of Taz in macrophages attenuated kidney fibrosis and macrophage M2 polarization in mice. Collectively, these results indicate that Wnt5a promotes kidney fibrosis by stimulating Yap/Taz-mediated macrophage M2 polarization.