Establishment of an Olfactory Region-specific Intranasal Delivery Technique in Mice to Target the Central Nervous System

We have recently developed a region-specific catheter-based intranasal application method in mice by using CT scan-based 3D cast models of the murine nose (DOI: 10.2376/0005-9366-17,102). This technique is able to specifically deliver drugs to the olfactory region or to the respiratory region only. Thereby, intranasally administered drugs could be delivered either via neuronal connections to the central nervous system or via the well-perfused rostral parts of the nasal mucosa to the systemic circulation. In the present study, we transferred successfully this novel delivery technique to C57Bl/6 mice and determined parameters such as insertions depth of the catheter and maximum delivery volume in dependence to the weight of the mouse. Breathing was simulated to verify that the volume remains at the targeted area. A step-by-step procedure including a video is presented to adopt this technique for standardized and reproducible intranasal central nervous system (CNS) delivery studies (DOI: 10.3390/pharmaceutics13111904).

How the mind comes to life: The physics and metaphysics of dissipative structures

This monograph tries to illuminate the process of live and mind by focusing on a thermodynamic perspective. In doing so a fundamental link is offered between psychology and neuroscience on the one hand and physics on the other hand. Non-equilibrium thermodynamics applied on human structures leads to explanations for highly complex processes like self-healing, the forecast of the structuring of stable neuronal connections or the importance of feedback loops for the formation of metastable neuronal structures. Besides energy there is evidence for the necessity of a second concept: information. To integrate this into a resilient ontology a new definition for „biological information” is required and will be provided. Transferring in analogy the thermodynamic framework of energy to biological information leads to what I shall call Dual Dissipation Theory (DDT). Its essentials will be presented and a short introduction, why dualism can be supported if introduced correctly. Finally, DDT suggests the following insight:The common concept for life is „energy flow“ and „information flow“, grounded in dissipative structures. It could offer a plausible heuristic for the explanation of mind and consciousness closing the gap from physics, i.e. non-ecquilibrium thermodynamics, to neuroscience and psychology.

Principal Components Analysis of EEG Signals for Epileptic Patient Identification

According to the behavior of its neuronal connections, it is possible to determine if the brain suffers from abnormalities such as epilepsy. This disease produces seizures and alters the patient’s behavior and lifestyle. Neurologists employ the electroencephalogram (EEG) to diagnose the disease through brain signals. Neurologists visually analyze these signals, recognizing patterns, to identify some indication of brain disorder that allows for the epilepsy diagnosis. This article proposes a study, based on the Fourier analysis, through fast Fourier transformation and principal component analysis, to quantitatively identify patterns to diagnose and differentiate between healthy patients and those with the disease. Subsequently, principal component analysis can be used to classify patients, employing frequency bands as the signal features. Besides, it is made a classification comparison before and after using principal component analysis. The classification is performed via logistic regression, with a reduction from 5 to 4 dimensions, as well as from 8 to 7, achieving an improvement when there are 7 dimensions in the precision, recall, and F1 score metrics. The best results obtained, without PCA are: precision 0.560, recall 0.690, and F1 score 0.620; meanwhile, the best values obtained using PCA are: precision 0.734, recall 0.787, and F1 score 0.776.

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.

Brain structural complexity and consciousness

Structure shapes function. Understanding what is structurally special about the brain that allows it to generate consciousness remains a fundamental scientific challenge. Recently, advances in brain imaging techniques have made it possible to measure the structure of human brain, from the morphology of neurons and neuronal connections to the gross anatomy of brain regions, in-vivo and non-invasively. Using advanced brain imaging techniques, it was discovered that the structural diversity between neurons and the topology of neuronal connections, as opposed to the sheer number of neurons or neuronal connections, are key to consciousness. When the structural diversity is high and the connections follow a modular topology, neurons will become functionally differentiable and functionally integrable with one another. The high levels of differentiation and integration, in turn, enable the brain to produce the richest conscious experiences from the smallest number of neurons and neuronal connections. Consequently, across individuals, those with a smaller brain volume but a higher structural diversity tend to have richer conscious experiences than those with a larger brain volume but a lower structural diversity. Moreover, within individuals, a reduction in neuronal connections, if accompanied by an increase in structural diversity, will result in richer conscious experiences, and vice versa. These findings suggest that having a larger number of neurons and neuronal connections is not necessarily beneficial for consciousness; in contrast, an optimal brain architecture for consciousness is one where the richest conscious experiences are generated from the smallest number of neurons and neuronal connections, at the minimal cost of biological material, physical space, and metabolic energy.

Microglia Regulate Neuronal Circuits in Homeostatic and High-Fat Diet-Induced Inflammatory Conditions

Microglia are brain resident macrophages, which actively survey the surrounding microenvironment and promote tissue homeostasis under physiological conditions. During this process, microglia participate in synaptic remodeling, neurogenesis, elimination of unwanted neurons and cellular debris. The complex interplay between microglia and neurons drives the formation of functional neuronal connections and maintains an optimal neural network. However, activation of microglia induced by chronic inflammation increases synaptic phagocytosis and leads to neuronal impairment or death. Microglial dysfunction is implicated in almost all brain diseases and leads to long-lasting functional deficiency, such as hippocampus-related cognitive decline and hypothalamus-associated energy imbalance (i.e., obesity). High-fat diet (HFD) consumption triggers mediobasal hypothalamic microglial activation and inflammation. Moreover, HFD-induced inflammation results in cognitive deficits by triggering hippocampal microglial activation. Here, we have summarized the current knowledge of microglial characteristics and biological functions and also reviewed the molecular mechanism of microglia in shaping neural circuitries mainly related to cognition and energy balance in homeostatic and diet-induced inflammatory conditions.

Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice

Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.

The Physiological Control of Eating: Signals, Neurons, and Networks

During the past 30 years, investigating the physiology of eating behaviors has generated a truly vast literature. This is fueled in part by a dramatic increase in obesity and its comorbidities that has coincided with an ever increasing sophistication of genetically based manipulations. These techniques have produced results with a remarkable level of cell-specificity-particularly at the cell signaling level-and have played a lead role in advancing the field. However, putting these findings into a brain-wide context that connects physiological signals and neurons to behavior and somatic physiology requires a thorough consideration of neuronal connections; a field that has also seen an extraordinary technological revolution. Our goal is to present a comprehensive and balanced assessment of how physiological signals associated with energy homeostasis interact at many brain levels to control eating behaviors. A major theme is that these signals engage sets of interacting neural networks throughout the brain, that are defined by specific neural connections. We begin by discussing some fundamental concepts-including ones that still engender vigorous debate-that provide the necessary frameworks for understanding how the brain controls meal initiation and termination. These include: key word definitions, ATP availability as the pivotal regulated variable in energy homeostasis, neuropeptide signaling, homeostatic and hedonic eating, and meal structure. Within this context, we discuss network models of how key regions in the endbrain (or telencephalon), hypothalamus, hindbrain, medulla, vagus nerve, and spinal cord work together with the gastrointestinal tract to enable the complex motor events that permit animals to eat in diverse situations.

BRAIN IN SPACE. HOW DOES SPACE AFFECT THE HUMAN BRAIN?

Introduction Nowadays more and more people and international companies are interested in Human Spaceflights. Aim and method In this review, the negative effects from space radiation, microgravity and the factor of isolation on the central nervous system will be described in relation to space neuroscience and the relevant studies examined. Results Space radiation can damage neuronal connections with both acute and chronic effects, manifested as altered cognitive function, reduced motor function, and behavioral changes. Moreover, some astronauts report a condition known as Spaceflight Associated Neuro-ocular Syndrome (SANS). The brain scans performed upon those astronauts, who came back from space travel suggest that due to reduced gravity conditions the brain and the fluids in the human body shift upwards, which increases pressure in the skull and may result in opticnerve swelling that causes blurred vision. Another interesting part of space neuroscience is the research of structural neuroplasticity. A study conducted on cosmonauts revealed an increase in the neuronal tissue of sensorimotor structures responsible for movement coordination. In addition to the space radiation and microgravity, long-term confinement also affects the microstructure of the brain white matter, which was proven in the study that used DTI (Diffusion Tensor Imaging). Conclusions To conclude, to continue understanding the risks posed by spaceflight to astronauts’ health research in the field of space neuroscience is important. In addition, the acquired insight could be relevant for terrestrial vestibular patients, patients with neurodegenerative disorders, as well as the elderly population, coping with neurological deficits. Keywords: space medicine, brain, space neuroscience, SANS, space radiation.