Nicolas Rouleau

Bio: Nicolas Rouleau is an academic researcher from Tufts University. The author has contributed to research in topics: Neuroscience & Induced pluripotent stem cell. The author has an hindex of 8, co-authored 42 publications receiving 268 citations. Previous affiliations of Nicolas Rouleau include Laurentian University & Algoma University.

A 3D human brain-like tissue model of herpes-induced Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive decline, memory loss, and inability to perform everyday functions. Hallmark features of AD-including generation of amyloid plaques, neurofibrillary tangles, gliosis, and inflammation in the brain-are well defined; however, the cause of the disease remains elusive. Growing evidence implicates pathogens in AD development, with herpes simplex virus type I (HSV-1) gaining increasing attention as a potential causative agent. Here, we describe a multidisciplinary approach to produce physiologically relevant human tissues to study AD using human-induced neural stem cells (hiNSCs) and HSV-1 infection in a 3D bioengineered brain model. We report a herpes-induced tissue model of AD that mimics human disease with multicellular amyloid plaque-like formations, gliosis, neuroinflammation, and decreased functionality, completely in the absence of any exogenous mediators of AD. This model will allow for future studies to identify potential downstream drug targets for treating this devastating disease.

A Long-Living Bioengineered Neural Tissue Platform to Study Neurodegeneration.

Abstract: The prevalence of dementia and other neurodegenerative diseases continues to rise as age demographics in the population shift, inspiring the development of long-term tissue culture systems with which to study chronic brain disease. Here, it is investigated whether a 3D bioengineered neural tissue model derived from human induced pluripotent stem cells (hiPSCs) can remain stable and functional for multiple years in culture. Silk-based scaffolds are seeded with neurons and glial cells derived from hiPSCs supplied by human donors who are either healthy or have been diagnosed with Alzheimer's disease. Cell retention and markers of stress remain stable for over 2 years. Diseased samples display decreased spontaneous electrical activity and a subset displays sporadic-like indicators of increased pathological β-amyloid and tau markers characteristic of Alzheimer's disease with concomitant increases in oxidative stress. It can be concluded that the long-term stability of the platform is suited to study chronic brain disease including neurodegeneration.

Electromagnetic fields as structure-function zeitgebers in biological systems: environmental orchestrations of morphogenesis and consciousness

Abstract: Within a cell system structure dictates function. Any interaction between cells, or a cell and its environment, has the potential to have long term implications on the function of a given cell and emerging cell aggregates. The structure and function of cells are continuously subjected to modification by electrical and chemical stimuli. However, biological systems are also subjected to an ever-present influence: the electromagnetic (EM) environment. Biological systems have the potential to be influenced by subtle energies which are exchanged at atomic and subatomic scales as EM phenomena. These energy exchanges have the potential to manifest at higher orders of discourse and affect the output (behavior) of a biological system. Here we describe theoretical and experimental evidence of EM influence on cells and the integration of whole systems. Even weak interactions between EM energies and biological systems display the potential to affect a developing system. We suggest the growing literature of EM effects on biological systems has significant implications to the cell and its functional aggregates.

Article Experimental Demonstration of Potential Entanglement of Brain Activity over 300 Km for Pairs of Subjects Sharing the Same Circular Rotating, Angular Accelerating Magnetic Fields: Verification by s_LORETA, QEEG Measurements

Abstract: In order to test the presence of excess correlation, or entanglement, pairs of subjects separated by 300 km were either exposed or not exposed to specific configurations of circular magnetic fields with changing angular velocities that dissociated the phase and group components. When one person in the pair was exposed to sound pulses but not to light flash frequencies within the classical electroencephalographic band, there were discrete changes in power within the cerebral space of the other person even though they were not aware of the stimulus times and separated by 300 km. The intracerebral changes that only occurred if the magnetic fields were activated around the two cerebrums simultaneously were discrete and involved about single, punctate volumes of about 0.13 cc (125 mm 3 ). The potential energy from the applied magnetic field within this volume was calculated to be about 6∙10 -14 J and with an average brain power frequency of 10 Hz would result in 6∙10 -13 W. Assuming π∙10 -2 m 2 for the surface area of the cerebrum, this is equivalent to ~2∙10 -11 W∙m -2 . This power density is the same order of magnitude as that associated with photon emission during cognition. Given the average of 6∙10 6 neurons per 125 mm 3 , the induced energy is equivalent to about 10 -20 J per neuron. This value can be considered a quantum of universal energy and would be congruent with a condition that could promote non-locality.

Modeling Controlled Cortical Impact Injury in 3D Brain-Like Tissue Cultures.

Abstract: Traumatic brain injury (TBI) survivors suffer long term from mental illness, neurodegeneration, and neuroinflammation. Studies of 3D tissue models have provided new insights into the pathobiology of many brain diseases. Here, a 3D in vitro contusion model is developed consisting of mouse cortical neurons grown on a silk scaffold embedded in collagen and used outcomes from an in vivo model for benchmarking. Molecular, cellular, and network events are characterized in response to controlled cortical impact (CCI). In this model, CCI induces degradation of neural network structure and function and release of glutamate, which are associated with the expression of programmed necrosis marker phosphorylated Mixed Lineage Kinase Domain Like Pseudokinase (pMLKL). Neurodegeneration is observed first in the directly impacted area and it subsequently spreads over time in 3D space. CCI reduces phosphorylated protein kinase B (pAKT) and Glycogen synthase kinase 3 beta (GSK3β) in neurons in vitro and in vivo, but discordant responses are observed in phosphprylated ribosomal S6 kinase (pS6) and phosphorylated Tau (pTau) expression. In summary, the 3D brain-like culture system mimicked many aspects of in vivo responses to CCI, providing evidence that the model can be used to study the molecular, cellular, and functional sequelae of TBI, opening up new possibilities for discovery of therapeutics.

SARS-CoV-2 targets neurons of 3D human brain organoids.

Abstract: COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS-CoV-2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS-CoV-2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS-CoV-2 and emphasize that brain organoids could model CNS pathologies of COVID-19.

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology.

Abstract: The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

The Evolution of Consciousness

Abstract: In this essay, I suggest that: (1) Consciousness (awareness) is a characteristic of all living things; (2) Consciousness evolved by Darwinian natural selection; (3) Consciousness is an emergent property, existing beyond its component parts; (4) Consciousness is essential to survival and reproductive success; (5) Consciousness exists in a hierarchy of complexity, from simple to sophisticated: (6) Consciousness is dynamic, varying according to the state of the organism; and (7) Machine consciousness (AIs) can exist only by emulating biological systems.