Crosstalk between adipose tissue and the microbiota-gut-brain axis in metabolic diseases

Recently, the microbiota-gut-brain axis (MGBA) has emerged as a target for therapeutic innovation. Impairment of dynamic relationships within the MGBA promotes the pathological features of metabolic diseases. However, experimental data on the MGBA has limited clinical application. This review summarizes recent studies and proposes that exploring the interaction among peripheral organs and the MGBA could verify the dominant role of the latter in the onset of metabolic diseases and promote the clinical application of research outcomes. We first emphasize the molecular basis of metabolic diseases caused by MGBA disorders, which manifests as bidirectional relationship. We also summarize related therapeutic strategies, along with limitations in their clinical application. Adipose tissue (AT) is dynamic during metabolic activities and might interact with components in the MGBA. Therefore, it is interesting to explore the interplay among the MGBA and different kinds of AT, including thermogenic adipose tissue and white adipose tissue (WAT). In addition, we also evaluate the functional specificity of adipose tissue derived mesenchymal stem cells (ADSCs) and the beige adipose tissue. Understanding the heterogeneity and molecular basis of the interaction between different kinds of AT and the MGBA could accelerate innovation in the diagnosis and therapy of metabolic diseases.     

粪菌移植通过微生物-肠-脑轴改善抑郁症的研究进展

人类粪菌移植(fecal microbiota transplantation,FMT)早在19世纪50年代的西方医学中便有临床应用.FMT已被证明可以很好地缓解艰难梭菌感染(Clostridium difficile infection,CDI)的胃肠道疾病,在调节微生物-肠-脑轴(microbiota-gut-br...     

肠道微生物菌群对脑及行为的影响

肠道微生物菌群组成的变化对正常生理的影响及其在疾病中的作用逐渐成为研究热点。肠道微生物菌群通过脑肠轴影响宿主生理学的各个方面,包括脑-肠交流、脑功能甚至行为。对无菌动物、被致病细菌感染的、使用益生菌或用抗生素药物的动物研究表明,肠道微生物菌群可以调节宿主焦虑样症状及行为。研究表明对肠道微生物菌群的调节可能是治疗复杂中枢神经系统失调症的新策略。     

Oxytocin,testosterone, and human social cognition

I describe an integrative social‐evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co‐opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness‐enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness‐reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self‐oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under‐developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively ‘hyper‐developed’ social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint effects partially mediate risks and phenotypes of autism and psychotic‐affective conditions. These considerations have direct implications for the development of therapies for alleviating disorders of social cognition, and for understanding how such disorders are associated with the evolution of human cognitive‐affective architecture.     

Going feral: Wild meat consumption and the uncanny in Melbourne,Australia

Feral animals are commonly constructed as the scourge of the Australian landscape. The transgressive act of introduced, domestic animals going wild elicits strong emotive responses within the community, often conceived in a kind of Freudian spectre of das unheimliche (the uncanny/unhomely), as the once familiar becomes uncontrolled, strange and frightening. Meanwhile, exponential global growth in human populations, and the resulting strain on the environment and food security, is necessitating the rethinking of meat consumption. In Australia, while the stigma surrounding feral animals has historically inhibited their consumption, feral meat is regarded by a growing body of advocates as an environmentally favourable alternative to farmed meat, allowing not only the avoidance of animal suffering within the industrial agriculture model, but also benefitting ecosystems through the removal of damage‐wreaking interlopers. This paper explores the feral turn and its contemporary manifestations as a growing food movement in Melbourne.     

Going against the grain: chemotaxis and infection in Vibrio cholerae

Chemotaxis is the process by which motile cells move in a biased manner both towards favourable and away from unfavourable environments. The requirement of this process for infection has been examined in several bacterial pathogens, including Vibrio cholerae. The single polar flagellum of Vibrio species is powered by a sodium-motive force across the inner membrane, and can rotate to produce speeds of up to 60 cell-body lengths (approximately 60microm) per second. Investigating the role of the chemotactic control of rapid flagellar motility during V. cholerae infection has revealed some unexpected and intriguing results.     

肠道菌群在脊髓损伤后胃肠道炎症反应中的研究进展

脊髓损伤(spinal cord injury, SCI)目前尚无有效的治疗手段。脊髓损伤后,患者常伴有严重的胃肠功能障碍,严重影响患者的生活质量。研究发现,脊髓损伤后肠道菌群的紊乱和脊髓损伤后的胃肠道功能障碍密切相关。因此,本文围绕脊髓损伤后肠道菌群的变化,探讨肠道菌群在迷走神经、下丘脑-垂体-肾上腺和肠道菌群代谢物3个途径中发挥的作用,及与胃肠道炎症反应相关的研究进展。     

海马——探索认知功能细胞分子机制的重要模型

哺乳动物脑中的海马结构被发现已经有几个世纪了,而初步确定其功能却是近几十年神经科学领域的重大发现．目前普遍认为海马是与记忆密切相关的,并把海马作为揭示学习记忆等认知过程细胞分子基础的重要模型．就近年在《生物化学与生物物理进展》上发表的相关文章进行了评论．     

The molecular genetics of cognition: dopamine, COMT and BDNF

The important contribution of genetic factors to the development of cognition and intelligence is widely acknowledged, but identification of these genes has proven to be difficult. Given a variety of evidence implicating the prefrontal cortex and its dopaminergic circuits in cognition, most of the research conducted to date has focused on genes regulating dopaminergic function. Here we review the genetic association studies carried out on catechol-O-methyltransferase (COMT) and the dopamine receptor genes, D1, D2 and D4. In addition, the evidence implicating another promising candidate gene, brain-derived neurotrophic factor (BDNF) in neuropsychological function, is assessed. Both the COMT val158met polymorphism and the BDNF val66met variant appear to influence cognitive function, but the specific neurocognitive processes involved continue to be a matter of debate. Part of the difficulty is distinguishing between false positives, pleiotropy and the influence of a general intelligence factor, g. Also at issue is the complexity of the relevant neuromolecular pathways, which make the inference of simple causal relationships difficult. The implications of molecular genetic cognitive research for psychiatry are discussed in light of these data.     

静电纺丝的主要参数对ＰＬＧＡ纤维支架形貌和纤维直径的影响

目的以聚乳酸-羟基乙酸共聚物(PLGA)为材料,采用静电纺丝方法制备纤维支架,考察制备参数对纤维支架结构及纤维直径的影响规律。方法以四氢呋喃(THF)和N,N-二甲基甲酰胺(DMF)的混合液为溶剂,调节PLGA溶液浓度、流量及电场强度分别制备了具有不同表面形貌的纤维支架。通过扫描电镜(SEM)观察了纺丝溶液的浓度、流量及电场强度对纤维形貌和直径的影响。同时在制备的PLGA纤维支架上接种了人的真皮成纤维细胞,并对细胞在PLGA支架上的黏附和增殖情况进行了研究,从而来评价支架材料的细胞相容性。结论结果表明,随着纺丝溶液浓度的增加,纤维直径逐渐增大,纤维直径的分布也随之增大。随着流量的增加,纤维直径略有增大。随着电场强度的增大,纤维直径没有明显的变化。但是电压和浓度的增大有助于减少珠丝的产生。体外细胞培养实验证明,制备的PLGA纤维支架能支持细胞正常的黏附和增殖活动。     

Without it no music: cognition,biology and evolution of musicality

Musicality can be defined as a natural, spontaneously developing trait based on and constrained by biology and cognition. Music, by contrast, can be defined as a social and cultural construct based on that very musicality. One critical challenge is to delineate the constituent elements of musicality. What biological and cognitive mechanisms are essential for perceiving, appreciating and making music? Progress in understanding the evolution of music cognition depends upon adequate characterization of the constituent mechanisms of musicality and the extent to which they are present in non-human species. We argue for the importance of identifying these mechanisms and delineating their functions and developmental course, as well as suggesting effective means of studying them in human and non-human animals. It is virtually impossible to underpin the evolutionary role of musicality as a whole, but a multicomponent perspective on musicality that emphasizes its constituent capacities, development and neural cognitive specificity is an excellent starting point for a research programme aimed at illuminating the origins and evolution of musical behaviour as an autonomous trait.     

The future of future-oriented cognition in non-humans: theory and the empirical case of the great apes

One of the most contested areas in the field of animal cognition is non-human future-oriented cognition. We critically examine key underlying assumptions in the debate, which is mainly preoccupied with certain dichotomous positions, the most prevalent being whether or not ‘real’ future orientation is uniquely human. We argue that future orientation is a theoretical construct threatening to lead research astray. Cognitive operations occur in the present moment and can be influenced only by prior causation and the environment, at the same time that most appear directed towards future outcomes. Regarding the current debate, future orientation becomes a question of where on various continua cognition becomes ‘truly’ future-oriented. We question both the assumption that episodic cognition is the most important process in future-oriented cognition and the assumption that future-oriented cognition is uniquely human. We review the studies on future-oriented cognition in the great apes to find little doubt that our closest relatives possess such ability. We conclude by urging that future-oriented cognition not be viewed as expression of some select set of skills. Instead, research into future-oriented cognition should be approached more like research into social and physical cognition.     

CSF prion protein concentration and cognition in patients with Alzheimer disease

Background/Objective: PrP^c has been suggested to play a role in AD pathophysiology. CSF concentrations of PrP^c have been shown to be reduced in AD compared with healthy controls. Furthermore, serum levels of PrP^c have recently been reported to be associated with the cognitive status of healthy elderly subjects. Therefore, we hypothesized that CSF levels of PrP^c could be associated with cognitive function of AD patients at the time of diagnosis.

Methods: AD patients (n = 114) included into an observational study underwent CERAD testing and lumbar puncture at time of diagnosis / study inclusion. CSF PrP^c was determined. Generalized linear models were fitted to assess the associations of PrP^c plus a variety of possible confounding factors and CERAD subscale measures.

Results: No association of CSF PrP^c and cognitive status could be established, while other factors (i.e., use of antipsychotic drugs, use of anti-dementia drugs, female sex, pre-progression time) were related to worse cognitive function in some domains.

Conclusion: CSF PrP^c appears not to be a useful biochemical surrogate of cognitive status in AD at the time of diagnosis. Follow-up analyses will examine possible associations with the speed of cognitive decline.     

Social cognition and psychopathology: a critical overview

The philosophical and interdisciplinary debate about the nature of social cognition, and the processes involved, has important implications for psychiatry. On one account, mindreading depends on making theoretical inferences about another person''s mental states based on knowledge of folk psychology, the so-called “theory theory” (TT). On a different account, “simulation theory” (ST), mindreading depends on simulating the other''s mental states within one''s own mental or motor system. A third approach, “interaction theory” (IT), looks to embodied processes (involving movement, gesture, facial expression, vocal intonation, etc.) and the dynamics of intersubjective interactions (joint attention, joint action, and processes not confined to an individual system) in highly contextualized situations to explain social cognition, and disruptions of these processes in some psychopathological conditions. In this paper, we present a brief summary of these three theoretical frameworks (TT, ST, IT). We then focus on impaired social abilities in autism and schizophrenia from the perspective of the three approaches. We discuss the limitations of such approaches in the scientific studies of these and other pathologies, and we close with a short reflection on the future of the field. In this regard we argue that, to the extent that TT, ST and IT offer explanations that capture different (limited) aspects of social cognition, a pluralist approach might be best.     

Human energetic stress associated with upregulation of spatial cognition

Objectives

Evolutionary life history theory has a unique potential to shed light on human adaptive capabilities. Ultra-endurance challenges are a valuable experimental model allowing the direct testing of phenotypic plasticity via physiological trade-offs in resource allocation. This enhances our understanding of how the body prioritizes different functions when energetically stressed. However, despite the central role played by the brain in both hominin evolution and metabolic budgeting, cognitive plasticity during energetic deficit remains unstudied.

Materials

We considered human cognitive plasticity under conditions of energetic deficit by evaluating variability in performance in three key cognitive domains. To achieve this, cognitive performance in a sample of 48 athletes (m = 29, f = 19) was assessed before and after competing in multiday ultramarathons.

Results

We demonstrate that under conditions of energetic deficit, performance in tasks of spatial working memory (which assessed ability to store location information, promoting landscape navigation and facilitating resource location and calorie acquisition) increased. In contrast, psychomotor speed (reaction time) remained unchanged and episodic memory performance (ability to recall information about specific events) decreased.

Discussion

We propose that prioritization of spatial working memory performance during conditions of negative energy balance represents an adaptive response due to its role in facilitating calorie acquisition. We discuss these results with reference to a human evolutionary trajectory centred around encephalisation. Encephalisation affords great plasticity, facilitating rapid responses tailored to specific environmental conditions, and allowing humans to increase their capabilities as a phenotypically plastic species.

     

The interplay of cognition and cooperation

Cooperation often involves behaviours that reduce immediate payoffs for actors. Delayed benefits have often been argued to pose problems for the evolution of cooperation because learning such contingencies may be difficult as partners may cheat in return. Therefore, the ability to achieve stable cooperation has often been linked to a species'' cognitive abilities, which is in turn linked to the evolution of increasingly complex central nervous systems. However, in their famous 1981 paper, Axelrod and Hamilton stated that in principle even bacteria could play a tit-for-tat strategy in an iterated Prisoner''s Dilemma. While to our knowledge this has not been documented, interspecific mutualisms are present in bacteria, plants and fungi. Moreover, many species which have evolved large brains in complex social environments lack convincing evidence in favour of reciprocity. What conditions must be fulfilled so that organisms with little to no brainpower, including plants and single-celled organisms, can, on average, gain benefits from interactions with partner species? On the other hand, what conditions favour the evolution of large brains and flexible behaviour, which includes the use of misinformation and so on? These questions are critical, as they begin to address why cognitive complexity would emerge when ‘simple’ cooperation is clearly sufficient in some cases. This paper spans the literature from bacteria to humans in our search for the key variables that link cooperation and deception to cognition.     

Challenging the classical notion of time in cognition: a quantum perspective

All mental representations change with time. A baseline intuition is that mental representations have specific values at different time points, which may be more or less accessible, depending on noise, forgetting processes, etc. We present a radical alternative, motivated by recent research using the mathematics from quantum theory for cognitive modelling. Such cognitive models raise the possibility that certain possibilities or events may be incompatible, so that perfect knowledge of one necessitates uncertainty for the others. In the context of time-dependence, in physics, this issue is explored with the so-called temporal Bell (TB) or Leggett–Garg inequalities. We consider in detail the theoretical and empirical challenges involved in exploring the TB inequalities in the context of cognitive systems. One interesting conclusion is that we believe the study of the TB inequalities to be empirically more constrained in psychology than in physics. Specifically, we show how the TB inequalities, as applied to cognitive systems, can be derived from two simple assumptions: cognitive realism and cognitive completeness. We discuss possible implications of putative violations of the TB inequalities for cognitive models and our understanding of time in cognition in general. Overall, this paper provides a surprising, novel direction in relation to how time should be conceptualized in cognition.