scholarly journals Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

2015 ◽  
Vol 95 (3) ◽  
pp. 785-807 ◽  
Author(s):  
Yuko Hara ◽  
Elizabeth M. Waters ◽  
Bruce S. McEwen ◽  
John H. Morrison
Keyword(s):  
Prefrontal Cortex ◽  
Cognitive Functions ◽  
Hormone Replacement ◽  
Brain Regions ◽  
The Body ◽  
Effective Interventions ◽  
Higher Cognitive Functions ◽  
Effects Of Aging ◽  
And Function ◽  
The Brain

Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.

Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function

1998 ◽  
Vol 28 (3) ◽  
pp. 655-663 ◽  
Author(s):  
P. NOPOULOS ◽  
M. FLAUM ◽  
S. ARNDT ◽  
N. ANDREASEN
Keyword(s):  
Psychosocial Adjustment ◽  
Cognitive Abilities ◽  
Economic Status ◽  
The Body ◽  
Abnormal Development ◽  
Control Group ◽  
Childhood And Adolescence ◽  
Lower Quartile ◽  
And Function ◽  
The Brain

Background. Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients?Methods. To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N=226) of male schizophrenics and a group of healthy male controls (N=142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height.Results. The patient group had a mean height of 177·1 cm, which was significantly shorter than the mean height of the control group of 179·4 (P<0·003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample.Conclusions. These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.

scholarly journals Impairments in Brain Bioenergetics in Aging and Tau Pathology: A Chicken and Egg Situation?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2531
Author(s):  
Amandine Grimm
Keyword(s):  
Brain Metabolism ◽  
Brain Aging ◽  
Cognitive Impairments ◽  
Tau Phosphorylation ◽  
The Body ◽  
Tau Pathology ◽  
Age Related ◽  
Energy Consuming ◽  
Effects Of Aging ◽  
The Brain

The brain is the most energy-consuming organ of the body and impairments in brain energy metabolism will affect neuronal functionality and viability. Brain aging is marked by defects in energetic metabolism. Abnormal tau protein is a hallmark of tauopathies, including Alzheimer’s disease (AD). Pathological tau was shown to induce bioenergetic impairments by affecting mitochondrial function. Although it is now clear that mutations in the tau-coding gene lead to tau pathology, the causes of abnormal tau phosphorylation and aggregation in non-familial tauopathies, such as sporadic AD, remain elusive. Strikingly, both tau pathology and brain hypometabolism correlate with cognitive impairments in AD. The aim of this review is to discuss the link between age-related decrease in brain metabolism and tau pathology. In particular, the following points will be discussed: (i) the common bioenergetic features observed during brain aging and tauopathies; (ii) how age-related bioenergetic defects affect tau pathology; (iii) the influence of lifestyle factors known to modulate brain bioenergetics on tau pathology. The findings compiled here suggest that age-related bioenergetic defects may trigger abnormal tau phosphorylation/aggregation and cognitive impairments after passing a pathological threshold. Understanding the effects of aging on brain metabolism may therefore help to identify disease-modifying strategies against tau-induced neurodegeneration.

Genealogy of the Cerebral Subject

Being Brains ◽  
2017 ◽  
Author(s):  
Fernando Vidal ◽  
Francisco Ortega
Keyword(s):  
Nineteenth Century ◽  
Functional Neuroimaging ◽  
The Body ◽  
Self Help ◽  
Brain Structure And Function ◽  
Cerebral Subject ◽  
The Individual ◽  
And Function ◽  
Cerebral Self ◽  
The Brain

The first chapter proposes to trace the distant roots of the cerebral subject to the late seventeenth century, and particularly to debates about the seat of the soul, the corpuscularian theory of matter, and John Locke’s philosophy of personal identity. In the wake of Locke, eighteenth century authors began to assert that the brain is the only part of the body we need to be ourselves. In the nineteenth century, this form of deterministic essentialism contributed to motivate research into brain structure and function, and in turn confirmed the brain-personhood nexus. Since then, from phrenology to functional neuroimaging, neuroscientific knowledge and representations have constituted a powerful support for prescriptive outlooks on the individual and society. “Neuroascesis,” as we call the business that sells programs of cerebral self-discipline, is a case in point, which this chapter also examines. It appeals to the brain and neuroscience as bases for its self-help recipes to enhance memory and reasoning, fight depression, anxiety and compulsions, improve sexual performance, achieve happiness, and even establish a direct contact with God. Yet underneath the neuro surface lie beliefs and even concrete instructions that can be traced to nineteenth-century hygiene manuals.

Amyloidosis

2013 ◽  
pp. 1397-1409
Author(s):  
Philip N. Hawkins
Keyword(s):  
Protein Misfolding ◽  
Solid Organ Transplantation ◽  
The Body ◽  
Solid Organ ◽  
Body Protein ◽  
Amyloid Deposits ◽  
Life Threatening ◽  
And Function ◽  
Protein Misfolding And Aggregation ◽  
The Brain

Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited in the interstitial space as insoluble and remarkably stable fibrils that progressively disrupt tissue structure and function of organs throughout the body. Protein misfolding and aggregation have increasingly been recognized in the pathogenesis of various other diseases, but amyloidosis—the disease directly caused by extracellular amyloid deposition—is a precise term with critical implications for patients with a specific group of life-threatening disorders. Amyloidosis may be acquired or hereditary and the pattern of organ involvement varies within and between types, though clinical phenotypes overlap greatly. Virtually any tissue other than the brain may be directly involved. Although histology remains the diagnostic gold standard, developments in scintigraphy and MRI technology often produce pathognomonic findings. Systemic amyloidosis is usually fatal, but the prognosis has improved as the result of increasingly effective treatments for many of the conditions that underlie it, notably the use of biologic anti-inflammatory agents in patients with AA amyloidosis and new immunomodulatory agents in patients with AL type. Better supportive care, including dialysis and solid organ transplantation, have also influenced the prognosis favourably. A range of specific novel therapies are currently in clinical development, including RNA inhibitors that suppress production of amyloid precursor proteins, drugs that promote their normal soluble conformation in the plasma, and immunotherapy approaches that directly target the amyloid deposits.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

scholarly journals Differential Expression of CD31 and Von Willebrand Factor on Endothelial Cells in Different Regions of the Human Brain: Potential Implications for Cerebral Malaria Pathogenesis

2020 ◽  
Vol 10 (1) ◽  
pp. 31 ◽  
Author(s):  
Smart Ikechukwu Mbagwu ◽  
Luis Filgueira
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Human Brain ◽  
Expression Pattern ◽  
Von Willebrand Factor ◽  
Brain Regions ◽  
And Function ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
The Brain

Cerebral microvascular endothelial cells (CMVECs) line the vascular system of the brain and are the chief cells in the formation and function of the blood brain barrier (BBB). These cells are heterogeneous along the cerebral vasculature and any dysfunctional state in these cells can result in a local loss of function of the BBB in any region of the brain. There is currently no report on the distribution and variation of the CMVECs in different brain regions in humans. This study investigated microcirculation in the adult human brain by the characterization of the expression pattern of brain endothelial cell markers in different brain regions. Five different brain regions consisting of the visual cortex, the hippocampus, the precentral gyrus, the postcentral gyrus, and the rhinal cortex obtained from three normal adult human brain specimens were studied and analyzed for the expression of the endothelial cell markers: cluster of differentiation 31 (CD31) and von-Willebrand-Factor (vWF) through immunohistochemistry. We observed differences in the expression pattern of CD31 and vWF between the gray matter and the white matter in the brain regions. Furthermore, there were also regional variations in the pattern of expression of the endothelial cell biomarkers. Thus, this suggests differences in the nature of vascularization in various regions of the human brain. These observations also suggest the existence of variation in structure and function of different brain regions, which could reflect in the pathophysiological outcomes in a diseased state.

Dennett, Functionalism, and Introspection

1985 ◽  
Vol 11 ◽  
pp. 55-83
Author(s):  
William Lyons
Keyword(s):  
Cognitive Functions ◽  
Higher Cognitive Functions ◽  
The Brain

Recent functionalist accounts of the mental, at least on the part of philosophers, have often been a result of dissatisfaction with the reductionist accounts championed by such physicalists as Place, Smart and Feigl. In particular this new account gained momentum from the growing belief that our map of the mental, at least in regard to the higher cognitive functions, does not seem to be a map of the brain and its processes. The more we find out about the working brain, the less we are able to cling to the belief that our talk about beliefs, evaluations, intentions, desires and motives gives us information about the structure or functioning of our brains.

scholarly journals Transgenic Mice Expressing Green Fluorescent Protein under the Control of the Corticotropin-Releasing Hormone Promoter

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5626-5632 ◽  
Author(s):  
Tamar Alon ◽  
Ligang Zhou ◽  
Cristian A. Pérez ◽  
Alastair S. Garfield ◽  
Jeffrey M. Friedman ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Artificial Chromosome ◽  
Brain Regions ◽  
Ingestive Behavior ◽  
Physiological Processes ◽  
Functional Relevance ◽  
Green Fluorescent ◽  
And Function ◽  
The Brain

Abstract CRH is widely expressed in the brain and is of broad functional relevance to a number of physiological processes, including stress response, parturition, immune response, and ingestive behavior. To delineate further the organization of the central CRH network, we generated mice expressing green fluorescent protein (GFP) under the control of the CRH promoter, using bacterial artificial chromosome technology. Here we validate CRH-GFP transgene expression within specific brain regions and confirm the distribution of central GFP-producing cells to faithfully recapitulate that of CRH-expressing cells. Furthermore, we confirm the functional integrity of a population of GFP-producing cells by demonstrating their apposite responsiveness to nutritional status. We anticipate that this transgenic model will lend itself as a highly tractable tool for the investigation of CRH expression and function in discrete brain regions.

scholarly journals The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
João Castelhano ◽  
Gisela Lima ◽  
Marta Teixeira ◽  
Carla Soares ◽  
Marta Pais ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Theory Of Mind ◽  
Molecular Mimicry ◽  
Meta Analysis ◽  
Temporal Cortex ◽  
Brain Regions ◽  
Imaging Studies ◽  
Activation Patterns ◽  
Therapeutic Benefits ◽  
The Brain

There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g., LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.

scholarly journals Integrating memories: Congruency and reactivation aid memory integration through reinstatement of prior knowledge

2019 ◽  
Author(s):  
Marlieke T.R. van Kesteren ◽  
Paul Rignanese ◽  
Pierre G. Gianferrara ◽  
Lydia Krabbendam ◽  
Martijn Meeter
Keyword(s):  
Prefrontal Cortex ◽  
Prior Knowledge ◽  
Medial Prefrontal Cortex ◽  
Medial Temporal Lobe ◽  
Knowledge Building ◽  
Activity Patterns ◽  
Brain Regions ◽  
Memory Integration ◽  
The Brain ◽  
Parahippocampal Place Area

AbstractBuilding consistent knowledge schemas that organize information and guide future learning is of great importance in everyday life. Such knowledge building is suggested to occur through reinstatement of prior knowledge during new learning in stimulus-specific brain regions. This process is proposed to yield integration of new with old memories, supported by the medial prefrontal cortex (mPFC) and medial temporal lobe (MTL). Possibly as a consequence, congruency of new information with prior knowledge is known to enhance subsequent memory. Yet, it is unknown how reactivation and congruency interact to optimize memory integration processes that lead to knowledge schemas. To investigate this question, we here used an adapted AB-AC inference paradigm in combination with functional Magnetic Resonance Imaging (fMRI). Participants first studied an AB-association followed by an AC-association, so B (a scene) and C (an object) were indirectly linked through their common association with A (an unknown pseudoword). BC-associations were either congruent or incongruent with prior knowledge (e.g. a bathduck or a hammer in a bathroom), and participants were asked to report subjective reactivation strength for B while learning AC. Behaviorally, both the congruency and reactivation measures enhanced memory integration. In the brain, these behavioral effects related to univariate and multivariate parametric effects of congruency and reactivation on activity patterns in the MTL, mPFC, and Parahippocampal Place Area (PPA). Moreover, mPFC exhibited larger connectivity with the PPA for more congruent associations. These outcomes provide insights into the neural mechanisms underlying memory integration enhancement, which can be important for educational learning.Significance statementHow does our brain build knowledge through integrating information that is learned at different periods in time? This question is important in everyday learning situations such as educational settings. Using an inference paradigm, we here set out to investigate how congruency with, and active reactivation of previously learned information affects memory integration processes in the brain. Both these factors were found to relate to activity in memory-related regions such as the medial prefrontal cortex (mPFC) and the hippocampus. Moreover, activity in the parahippocampal place area (PPA), assumed to reflect reinstatement of the previously learned associate, was found to predict subjective reactivation strength. These results show how we can moderate memory integration processes to enhance subsequent knowledge building.

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