Neuroscience and Neurobiology Commons^™

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic And Ca2+-Handling Deficits In Alzheimer's Disease Models, Erez Eitan, Emmette R. Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M. Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A. Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W. Witwer, Dimitrios Kapogiannis, Mark P. Mattson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca²⁺ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an …

From The Handbook Of The Laszlo Institute Of New Paradigm Research And The Intelligence Of The Cosmos , Inner Traditions, September 2017, Ervin Laszlo

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Consciousness: Where We Are At, Imants Barušs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

It is useful every couple of years to take a bird’s eye view of consciousness studies and reflect on what we see. When I look, I still see two streams, one of which is the social and political framework for the study of consciousness, and the other of which is the substance of what we know about consciousness. The former is still largely defined by the extent to which the scientific study of consciousness has been freed from a materialist agenda. The latter includes recent research into the clarity of cognitive functioning in the absence of sufficient neurological support for …

Growth And Happiness In The Human Personality, Rien Havens, Allan Combs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

This paper explores stages and styles of meaning making in a population at Kegan’s (1982) developmental levels 3 through 5. It is a qualitative study of the relationship between adult personality development and how individuals speak about meaning and well-being in their lives. Nineteen participants ranging widely in age and socioeconomic class were selected informally through connections with the researchers, and snowball sampling. They were chosen from an original group of 50, based on informal interviews suggesting that they had achieved Kegan’s developmental levels of “Socialized Mind” (stage 3), or especially “Self-Authoring Mind” (stage 4) or “Self-Transforming Mind” (stage 5). …

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Joe Subbiondo

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Allan Combs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Ervin Laszlo

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Jim Smith

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Stanley Krippner

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Shelli Joye

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID …

The Pribram – Bohm Hypothesis Part Ii: The Physiology Of Consciousness, Shelli R. Joye

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

A physiology of consciousness is elaborated, based upon implications of the Pribram-Bohm hypothesis (developed in Part I of this series). The model presented here is in sharp contrast to the prevailing conviction among neuroscientists that consciousness will eventually be discovered to be a physiological epiphenomenon of neuronal electrical impulses firing in the brain. In contrast, the Pribram-Bohm theory holds that consciousness, inherent in what Bohm views cosmologically as “the Whole,” manifests as a dynamic conscious energy resonance bridging the explicate space-time domain with the nonlocal, transcendent flux domain termed the “implicate order.” Presented in Part I, the Pribram-Bohm hypothesis posits …

Integral In-Dwelling: A Prepositional Theology Of Religions, Bruce Alderman

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

The concept of generalized co-presence is a central one in the gram- mar of Bhaskar’s metaRealist metaphysics. As a term denoting the radical relationality and mutual indwelling of beings in the cosmos, generalized co- presence finds analogues in the holographic principle of Morin’s Complex Thought, Wilber’s nondual inflection of holarchy, as well as multiple religious archetypes of divine interindependence. In this paper, I will explore the potential of this concept for framing a “deep participatory,” Complex Integral Realist model of interreligious relationship that can amplify the integrative potential of the metaRealist, Integral, and participatory approaches to this topic that have …

Why Consciousness Matters: Insights From A New Generation, Kathleen Noble

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

The University of Washington-Bothell is home to a transdisciplinary and integral minor in consciousness that is the first and only such program at a public research university. This study reports a content analysis of reflection essays submitted by 122 students who completed at least four of the five courses that comprise the minor between 2012 and 2016. Results indicate that students derived significant benefits from this approach to the study of consciousness, including a deep appreciation for the depth and breadth of the mind and the need to release their understanding of consciousness from the constraints of scientific materialism. They …

Commentaries On Deepak Chopra And Menas Kafatos’ Book, “You Are The Universe”; 2017, Harmony Books., Simon Senzon

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

The Person And The Self As Social Accomplishment, Leslie Irvine

Animal Sentience

Rowlands (2016) presents a compelling argument for extending personhood to nonhuman animals. Sociological conceptions of the person also do not require that animals meet the elusive standard of self-awareness. Sociological ideas on selfhood support the claims about pre-reflective awareness and extend the requisite experiences to animals.

Interaction Of Tau With The Rna-Binding Protein Tia1 Regulates Tau Pathophysiology And Toxicity, Tara Vanderweyde, Daniel J. Apicco, Katherine Youmans-Kidder, Peter E. A. Ash, Casey Cook, Edroaldo Lummertz Da Rocha, Karen Jansen-West, Alissa A. Frame, Allison Citro, John D. Leszyk, Pavel Ivanov, Jose F. Abisambra, Martin Steffen, Hu Li, Leonard Petrucelli, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Thoughts On Consciousness And The Original Photons, Henryk Skolimowski

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Premises Of A Natural Science Of Consciousness, Ervin Laszlo

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

According to the mainstream of modern science, there cannot be a natural science of consciousness because consciousness does not actually exist in nature. It is a product or by-product of the workings of the brain. There is a natural science of brain and the nervous system, for these are bona fide elements of the world, but there cannot be a natural science of a phenomenon of which the very existence is in question. In the prevalent view con2sciousness is something that happens when neurons fire in the brain. This is said to be confirmed by experience. There is no consciousness …

Presence And The Paradox Of Love, Joanne Burtch

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

Spiritual experiences often seem unrelated to the intellectual orientation of science. However, some discussion of the laboratory study of spiritual practice does attempt to include the mystery and the human experience in its dialogue. An exploration of the paradox of love demonstrates how it might be possible to find a relationship between the scientific understanding of spirituality and the profundity of spiritual experience.

On The Significance Of Psychodynamic Discourse For The Field Of Consciousness Studies, Robin S. Brown

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

Despite the obvious confluence of concerns between psychodynamic psychology and the emerging field of consciousness studies, the extent to which psychodynamic thinking has factored into the consciousness literature has been limited. With widespread interest in “the unconscious” having significantly diminished, the present paper asks what might be implied in the shift towards the notion of “consciousness”—what about this cross-disciplinary designation has come to attract attention not only within the academic world, but also in the popular press? That the term does indeed invite contributions from a variety of disciplines makes the field both a meeting space, and a battleground. It …

Eugene Taylor: An Appreciation, Simon Senzon

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

By sharing Professor Taylor’s impact on me with you in this way, I hope to offer a glimpse of the depth he pointed us to. Rather than just tell you his stories and his theories, I am sharing layers of my own experience both in similar synchronicities from my own personal mythology and also the meaning I make for myself as I go deeper in understanding what he was really teaching. If you can see that I am sharing something beyond the words themselves, then you know what he meant by soteriological writing. The words are used to help you …

Sarath, Edward W. (2013). Improvisation, Creativity, And Consciousness: Jazz As Integral Template For Music, Education, And Society. Albany, Ny: State University Of New York., Lynne Roff

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

No abstract provided.

Beyond Perennialist And Participatory Spiritualities: Transformation And Culture, Joanne Burtch

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

A comparison of perennialism, participatory spirituality, and Gebser’s structures of consciousness demonstrates how deeper inquiry is required to understand how perennialism and participatory spirituality would address the relationship between individuals and culture with regard to how transformation happens. By reviewing how each of these philosophies approach context, the interpersonal, transformation, cultural relativity, pluralism, and multiplicity, the article identifies ambiguities that offer perennialism and participatory spirituality scholars the opportunity to explore their suppositions about spirituality more deeply.

Consciousness Studies – An Overview, Allan Combs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

This essay is a survey of the field of consciousness studies, its history, scope, and a little about its future. It’s principal focus is on Western thinking about consciousness beginning in classical times and continuing down to the present. It highlights and briefly describes major streams of thought including ideas from ancient Greece, German Idealism, British Empiricism, 20^th century European phenomenology, and important contemporary areas of research and scholarship. These include American pragmatism, developmental psychology, transpersonalism, analytic philosophy, computationalism, neural networks, and physics. The essay also briefly explores possible future trends in the study of consciousness.

Reembodying, Human Consciousness In The Earth, John Briggs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

For the last 20,000 years or so the dominant mode of human consciousness has been one that divides reality into subjects and objects, and focuses on human desires and needs. This anthropocentric mode of consciousness has invented religions, built civilizations, amassed knowledge, and developed technology and science. It has also disembodied us from the Earth and led to the Anthropocene Era. Still with us is another mode of human consciousness that arguably once existed in a balance with the anthropocentric mode during our long hunter-gatherer, Paleolithic sojourn. This holistic, integrative mode of consciousness experiences the Earth as a mother, and …

The Pribram – Bohm Hypothesis, Shelli R. Joye

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

A holoflux theory of consciousness as modulated energy is hypothesized and shown to support both local and non-local properties. This thesis emerges from an integral evaluation of evidence drawn from: (1) the holonomic mind/brain theories of Karl Pribram, (2) the ontological interpretation of quantum theory by David Bohm. Applying an integral methodology to superimpose and correlate seemingly disparate concepts from among these sources and others, a composite-theory emerges, a “holoflux” theory of consciousness, after the term favored by Karl Pribram to describe David Bohm’s “holomovement” between an explicate order andan implicate order. This Pribram–Bohm composite holoflux theory is shown to …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …