Stress: Putting the Brain Back Into Medicine

Throughout the life course stress plays a major role in health and disease. Although it has long been known that the brain orchestrates the many ways that the body responds to these experiences, a gap exists between health care providers who focus from the head up and those who focus on the head down

Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals.

Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia

Psychobiological factors of resilience and depression in late life.

In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind-body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD

What contributes to individual differences in brain structure?

Individual differences in adult human brain structure have been found to reveal a great deal of information about variability in behaviors, cognitive abilities and mental and physical health. Driven by such evidence, what contributes to individual variation in brain structure has gained accelerated attention as a research question. Findings thus far appear to support the notion that an individual’s brain architecture is determined largely by genetic and environmental influences. This review aims to evaluate the empirical literature on whether and how genes and the environment contribute to individual differences in brain structure. It first considers how genetic and environmental effects may separately contribute to brain morphology, by examining evidence from twin, genome-wide association, cross-sectional and longitudinal studies. Next, evidence for the influence of the complex interplay between genetic and environmental factors, characterized as gene-environment interactions and correlations, is reviewed. In evaluating the extant literature, this review will conclude that both genetic and environmental factors play critical roles in contributing to individual variability in brain structure

Pre-reproductive parental enriching experiences influence progeny’s developmental trajectories

While the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring's phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral trait

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

Bidirectional Influence of Epinephrine on Hippocampal LTP via β-Adrenergic Receptors

The formation and storage of memories within the brain remains a subject that is not well understood. The hippocampus has been identified by many studies as a likely center for memory formation (Lynch, 2004), and further research into this subject has begun to suggest that synaptic plasticity in the hippocampus could be partly responsible for the physical changes in the brain, which underlie memory formation. Long Term Potentiation is a form of synaptic plasticity, and is considered to be a physical increase in the strength of connection between neurons or groups of neurons. Much like memories, the duration of a given LTP can last anywhere from minutes to years, depending upon the conditions under which the LTP was induced. Stress, in particular, has been found to either enhance or impair LTP formation, under different conditions. The brain’s response to stress, or any kind of emotional arousal, is in part mediated by the release of the hormone epinephrine. This type of “stress memory”, or epinephrine-mediated memory formation, is important because it could explain the pathological memory formation that is commonly seen in phenomena such as Post Traumatic Stress Disorder (Korol and Gold, 2008). Epinephrine release in the periphery has been seen to influence LTP in the hippocampus, however epinephrine itself cannot enter the brain. These experiments served to explore the mechanisms by which epinephrine can act to bidirectionally influence hippocampal LTP through activation of β-adrenergic receptors

Cognitive enhancing effects of voluntary exercise, caloric restriction and environmental enrichment: A role for adult hippocampal neurogenesis and pattern separation?

Several behavioural interventions, such as physical exercise, dietary restriction, and enriched environments are associated with both improved cognition and increased adult hippocampal neurogenesis. Whether the learning and memory improvements associated with these interventions are causally dependent on the upregulated neurogenesis has not yet been conclusively determined. However, with the accumulating evidence of a role for adult-born hippocampal neurons in spatial pattern separation, it is possible that the improvements in learning and memory result, at least in part, from an improvement in pattern separation. The following review focuses on three major behavioural manipulations associated with cognitive enhancement: voluntary exercise, caloric restriction, and environmental enrichment (including learning), and how increased neurogenesis may contribute to the enhancement by improving pattern separation.The authors would like to acknowledge financial contribution from the following funding sources: the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008, of which resources are composed of a European Federation of Pharmaceutical Industries and Associations in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013); The Wellcome Trust/Medical Research Council (089703/Z/09/Z) and the Biotechnology and Biological Sciences Research Council (grant BB/G019002/1). C.A.O. received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 603016. B.A.K. was supported by Gates Cambridge.This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S235215461500087X

Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review

Background A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer’s disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes. Objective To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes. Search strategy Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine’s antidementia activities were identified using “berberine” and “dementia” as search terms. In search B, recent studies on berberine’s effects on diabetes were surveyed using “berberine” and “diabetes” as search terms. Inclusion criteria Clinical and preclinical studies that investigated berberine’s effects associated with MetS and cognitive dysfunction were included. Data extraction and analysis Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors. Results In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating β-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia. Conclusion Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS