Brain Physiology Research Articles

74 Timed Motor Performance in Children Medically Cleared for Return to Activities Post Mild Traumatic Brain Injury

Objective:Children who sustain a mild traumatic brain injury (mTBI) are at increased odds of additive injury and continue to show altered motor performance relative to never-injured peers after being medically cleared (MC) to return to normal activities. There is a critical need to determine when children can return to activities without risk of short and long-term adverse effects, with research showing high reinjury rates for 3-12 months after RTP. The Physical and Neurological Examination for Subtle Signs (PANESS) measures subtle signs of motor impairment during gait, balance, and timed motor functions. Recent literature has demonstrated that PANESS timed motor function can distinguish between children medically cleared post-mTBI compared to never-injured controls. The present study examined performance on timed motor tasks in youth medically cleared from mTBI following medical clearance and 3-months later, compared to never-injured peers.Participants and Methods:25 children (Mage=14.16, SD=2.46; Male=68%) were enrolled within 6 weeks of medical clearance from mTBI (Mdays post MC=33, SD=13.4, Range=2-59) along with 66 typically developing, never-injured controls (Mage=13.9, SD=2.22; Male=50%). Group differences were evaluated for the Timed Motor section of the PANESS at enrollment and at a 3-month follow-up (Mdays from enrollment to follow-up=95.90, SD=12.69, Range=62-129). This 3-month follow-up occurred on average 4 months after medical clearance (Mdays from MC to follow-up=130.08, SD=17.58, Range=92 - 164). The Timed Motor section includes Repetitive (foot tapping, hand patting, and finger tapping) and Sequential (heel-toe rocking, hand pronate/supinate, finger sequencing) raw time scores, measured in seconds. The Total Timed Motor Speed score is the combination of Repetitive and Sequential Movement and the side-to-side tongue item.Results:At 3-month follow-up, mTBI participants (M=67.55, SD=8.26, Range=53.66-83.88) performed worse than controls (M=63.09, SD=10.23, Range=39.86-100.51) on Total Timed Motor Speed, t(89)= 1.95, p<0.05), including when controlling for age and sex, F(1, 87)=4.67, p<0.05. At the same time point, mTBI participants (M=36.54, SD=5.47, Range=28.74-49.17) performed worse on Sequential Speed than controls (M=32.93, SD=6.1, Range=21.49-56.76), t(89)=2.59, p<0.01, including when controlling for age and sex, F(1, 87)=7.687, p<0.01). Although groups performed similarly on Sequential Speed at the initial time point, mTBI participants exhibited a trend of less improvement from initial to follow-up (MmTBI=-1.69, Mcontrol=-3.68, t(90)=1.445, p=0.076).Conclusions:Although groups did not significantly differ on Timed Motor Speed items at the initial time point, the mTBI group showed consistently lower scores than controls at both time points and less improvement over time. Results indicate that Total Timed Motor Speed, specifically Sequential Speed, may be a sensitive marker of persisting differences in high-level motor and cognitive learning/control in children who have been medically cleared after mTBI. More data are needed to evaluate these findings over a longer time period, and future studies should examine behavioral markers concurrently with physiologic brain recovery over time.

Prediction Of Seizures In Patients With Temporal Lobe Epilepsy, More Than 30 Minutes Before Onset.

Dear Madam, Around 52.5 million people worldwide suffer from the neurological illness known as epilepsy, which is frequently characterized by recurring seizures. (1, 2) As epilepsy is a chronic disorder that can lead to cognitive deficits, sadness, and anxiety in sufferers, it has a considerable negative impact on individuals and society. The most common type of seizures, affecting around 61% of persons with epilepsy, are focal seizures, which raise the risk of injury and early death (2). One of the most common forms of focal epilepsy, temporal lobe epilepsy (TLE), is characterized by recurring spontaneous seizures that begin in the temporal lobe. (s). (3) In the last two decades, many new antiseizure medications (ASMs)have been developed; however, about 40% of people with epilepsy may be drug-resistant, meaning ASMs are unable to control their seizures; therefore, despite the advent of new treatments, a high unmet need remains unaddressed. (2) Surgery is an alternate treatment, however, it cannot be used if larger areas of the brain are affected, in such cases, neuromodulation is a novel and successful therapeutic tool developed. (4) Conventionally, neural activity in epilepsy is categorized into interictal, and post-ictal states. With the help of continuous EEG, researchers have subdivided interictal state into a pre-ictal and pro-ictal state in temporal lobe epilepsy patients (which is the typical drug-resistant focal epilepsy targeted for interventions such as neuromodulation). The pre-ictal states indicate imminent seizure onset, while pro-ictal states reflect changes in neural activity that create a propensity for seizures over longer periods. The EEG-based pro-ictal state detection is critical to adaptive neuromodulation, with early detection of seizure allowing electrodes to be applied therapeutically to the brain's seizure onset zone and thalamus enabling treatment to be modified as per seizure risk. (5) A prospective cohort study was conducted on adults with drug-resistant temporal lobe epilepsy at UTHealth Houston, in which pro-ictal state – i.e., pathologic brain activities during periods of heightened seizure risk could be detected up to one-half hour prior to seizure onset. A classifier was developed that could reasonably accurately distinguish between physiological and pathologic brain states in temporal lobe epilepsy. Thalamocortical dynamics were used to identify pro-ictal states in each patient. As the limbic thalamus exerts a diverse influence on cortex activity, thalamocortical EEG was used for pro-ictal state detection as opposed to previous paradigms derived solely from cortical structures. ---Continue

Structural neural correlates of mental fatigue and reward-induced improvement in performance

Neuroimaging studies investigating the association between mental fatigue (henceforth fatigue) and brain physiology have identified many brain regions that may underly the cognitive changes induced by fatigue. These studies focused on the functional changes and functional connectivity of the brain relating to fatigue. The structural correlates of fatigue, however, have received little attention. To fill this gap, this study explored the associations of fatigue with cortical thickness of frontal and parietal regions. In addition, we aimed to explore the associations between reward-induced improvement in performance and neuroanatomical markers in fatigued individuals. Thirty-nine healthy volunteers performed the psychomotor vigilance task for 15 min (i.e., 3 time-on-task blocks of 5 min) out of scanner; followed by an additional rewarded block of the task lasting 5 min. Baseline high-resolution T1-weigthed MR images were obtained. Reaction time increased with time-on-task but got faster again in the rewarded block. Participants’ subjective fatigue increased during task performance. In addition, we found that higher increase in subjective mental fatigue was associated with the cortical thickness of the following areas: bilateral precuneus, right precentral gyrus; right pars triangularis and left superior frontal gyrus. Our results suggest that individual differences in subjective mental fatigue may be explained by differences in the degree of cortical thickness of areas that are associated with motor processes, executive functions, intrinsic alertness and are parts of the default mode network.

An Astyanax mexicanus mao knockout line uncovers the developmental roles of monoamine homeostasis in fish brain.

Monoaminergic systems are conserved in vertebrates, yet they present variations in neuroanatomy, genetic components and functions across species. MonoAmine Oxidase, or MAO, is the enzyme responsible for monoamine degradation. While mammals possess two genes, MAO-A and MAO-B, fish possess one single mao gene. To study the function of MAO and monoamine homeostasis on fish brain development and physiology, here we have generated a mao knockout line in Astyanax mexicanus (surface fish), by CRISPR/Cas9 technology. Homozygote mao knockout larvae died at 13 days post-fertilization. Through a time-course analysis, we report that hypothalamic serotonergic neurons undergo fine and dynamic regulation of serotonin level upon loss of mao function, in contrast to those in the raphe, which showed continuously increased serotonin levels - as expected. Dopaminergic neurons were not affected by mao loss-of-function. At behavioral level, knockout fry showed a transient decrease in locomotion that followed the variations in the hypothalamus serotonin neuronal levels. Finally, we discovered a drastic effect of mao knockout on brain progenitors proliferation in the telencephalon and hypothalamus, including a reduction in the number of proliferative cells and an increase of the cell cycle length. Altogether, our results show that MAO has multiple and varied effects on Astyanax mexicanus brain development. Mostly, they bring novel support to the idea that serotonergic neurons in the hypothalamus and raphe of the fish brain are different in nature and identity, and they unravel a link between monoaminergic homeostasis and brain growth.

The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.

Astrocytes are glial cells that perform several fundamental physiological functions within the brain. They can control neuronal activity and levels of ions and neurotransmitters, and release several factors that modulate the brain environment. Over the past few decades, our knowledge of astrocytes and their functions has rapidly evolved. Neurodegenerative diseases are characterized by selective degeneration of neurons, increased glial activation, and glial dysfunction. Given the significant role played by astrocytes, there is growing interest in their potential therapeutic role. However, defining their contribution to neurodegeneration is more complex than was previously thought. This review summarizes the main functions of astrocytes and their involvement in neurodegenerative diseases, highlighting their neurotoxic and neuroprotective ability.

BDNF and Lactate as Modulators of Hippocampal CA3 Network Physiology.

Growing evidence supports the notion that brain-derived neurotrophic factor (BDNF) and lactate are potent modulators of mammalian brain function. The modulatory actions of those biomolecules influence a wide range of neuronal responses, from the shaping of neuronal excitability to the induction and expression of structural and synaptic plasticity. The biological actions of BDNF and lactate are mediated by their cognate receptors and specific transporters located in the neuronal membrane. Canonical functions of BDNF occur via the tropomyosin-related kinase B receptor (TrkB), whereas lactate acts via monocarboxylate transporters or the hydroxycarboxylic acid receptor 1 (HCAR1). Both receptors are highly expressed in the central nervous system, and some of their physiological actions are particularly well characterized in the hippocampus, a brain structure involved in the neurophysiology of learning and memory. The multifarious neuronal circuitry between the axons of the dentate gyrus granule cells, mossy fibers (MF), and pyramidal neurons of area CA3 is of great interest given its role in specific mnemonic processes and involvement in a growing number of brain disorders. Whereas the modulation exerted by BDNF via TrkB has been extensively studied, the influence of lactate via HCAR1 on the properties of the MF-CA3 circuit is an emerging field. In this review, we discuss the role of both systems in the modulation of brain physiology, with emphasis on the hippocampal CA3 network. We complement this review with original data that suggest cross-modulation is exerted by these two independent neuromodulatory systems.

Gravitational Ischemia in the Brain: How Interfering with Its Release May Predispose to Either Alzheimer’s- or Parkinson’s-like Illness, Treatable with Hyperbaric Oxygen

The physiological mechanisms for releasing and resolving gravitational ischemia in the brain, and their susceptibility to malfunction, may play an important role in a variety of neurological illnesses. An astronaut on a space walk in a micro-gravity environment may be susceptible to neuro-ocular symptoms associated with unopposed gravity-resistance mechanisms for partially preventing gravitational ischemia in the brain, and for attenuating its impact—mechanisms which may be required for normal brain physiology on Earth. Astronauts on the International Space Station typically breathe a mixture of gasses similar in composition to what they breathed on Earth, following the 1967 death of three astronauts, including Ed White, by fire on the Apollo 1 spacecraft, which was carrying 100% oxygen. For the last decade, astronauts have been studied extensively by flight physicians regarding the commonly experienced symptoms of VIIP, or ‘visual impairment and intracranial pressure’ syndrome. In this paper, we compare VIIP syndrome to the neuro-ocular and Parkinson’s-like symptoms which occurred during and after the 1918–1919 influenza pandemic. The common denominator may be gravitational ischemia in the brain, and the mirror-imaging failed mechanisms for its release (in influenza) versus unopposed gravity-resistance mechanisms (in astronauts). Some research has suggested that astronauts may benefit from breathing oxygen concentrations somewhat higher than 20%, and under slightly elevated pressure. These may possibly prevent maladaptive mechanisms leading to Alzheimer’s- or Parkinson’s-like illness by compensating for impaired mechanisms for releasing and resolving gravitational ischemia in the brain.

Altered neural processes underlying executive function in occupational burnout-Basis for a novel EEG biomarker.

As burnout has become a global pandemic, there is a call for improved understanding and detection of alterations in brain functions related to it. We have previously reported challenges in executive functions (EFs) in daily life, especially in metacognition, in subjects with occupational burnout, along with alterations in cardiac physiology. In the current study, we focused on the impact of burnout on brain physiology during a task requiring EF. Fifty-four volunteers filled in inventories of burnout, depression, and EF in daily life (BBI-15, BDI, and BRIEF-A). Based on the BBI-15 score, subjects were divided into burnout and non-burnout groups. Subjects performed a Go/NoGo test (Executive RT test) engaging several EFs, while their EEG was recorded. The inventory scores, cognitive performance scores, and event-related potential (N2, P3) amplitudes, latencies, and interpeak latencies (IPLs) were compared between the groups. There were significant differences in the BDI and BRIEF-A scores between the groups, with more symptoms of depression and challenges in daily life in the burnout group. There were no differences in objective performance measures in the EF task between the groups. However, centroparietal P3 amplitude was larger, and while there were no differences in N2 or P3 latencies, N2-P3 IPL was longer in the Go condition in the burnout than in non-burnout group. Both ERP measures correlated significantly with burnout symptoms. A regression model from centroparietal P3 amplitude and N2-P3 IPL predicted significantly both the BBI-15 score and the BRIEF-A metacognition index. We conclude that burnout is linked with challenges in EF in daily life and alterations in the underlying neural processes. While cognitive performance in the task was equal, electrophysiological measures differed between the groups. Prolonged N2-P3 IPL points toward slowed transition from one cognitive process to another. Increased P3 amplitude, on the other hand, reflects increased allocation of neural processing resources. This may be a compensatory mechanism, allowing for equal performance with controls. These electrophysiological measures, obtained during the EF task, show promise as brain physiology-based biomarkers of burnout, contributing to its improved and objective detection. In addition, these results indicate occupational burnout is linked with objective alterations in brain physiology.

Chronic pharmacological activation of SERCA with CDN1163 affects spatial cognitive flexibility but not attention and impulsivity in mice.

Intracellular calcium (Ca2+) homeostasis is critical for many neural processes, including learning, memory and synaptic plasticity. The sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) is among the key regulators that preserve Ca2+ homeostasis in neurons. SERCAs comprise a set of ubiquitously expressed Ca2+ pumps that primarily function to sequester cytosolic Ca2+ into endoplasmic reticular stores. As SERCA has been implicated in the neurobiology of several neuropsychiatric and neurodegenerative diseases, pharmacological harnessing of its function is critical in understanding SERCA's role in brain physiology and pathophysiology. In the current study, we employed the Morris water maze and 5-choice serial reaction time task (5-CSRTT) to investigate the effects of chronic pharmacological activation of SERCA, using the small allosteric SERCA activator CDN1163, on spatial learning and memory, and executive functioning in naive C57BL/6J mice. Our data show that chronic pharmacological SERCA activation with CDN1163 (20 mg/kg) selectively impairs spatial cognitive flexibility and reversal learning in the Morris water maze while leaving executive functions such as attention and impulsivity intact. Present findings contribute to the growing field of the role of SERCA function in the brain and behavior and expand current knowledge on the use of the small allosteric activator CDN1163 as an investigational tool to study the role of SERCA in regulating neurobehavioral processes and as a potential therapeutic candidate for debilitating brain disorders.

Fluid therapy in the acute brain injured patient.

Adequate fluid therapy in the acute brain injured (ABI) patient is essential for maintaining an adequate brain and systemic physiology and preventing intra- and extracranial complications. The target of euvolemia, implying avoidance of both hypovolemia and fluid overloading (or "hypervolemia," by definition associated with fluid extravasation leading to tissue edema) is of key importance. Primary brain injury can be aggravated by secondary brain injury and systemic deterioration through diverse pathways which can challenge appropriate fluid management, e.g. neuroendocrine and electrolyte disorders, stress cardiomyopathy (also known as cardiac stunning) and neurogenic pulmonary edema. This is an updated expert opinion aiming to provide a practical overview on fluid therapy in the ABI patient, partly based on more recent work and stressing the fact that intravenous fluids should be regarded as drugs, with their inherent potential for both benefit and (unintended) harm.

Delta-alpha cross-frequency coupling for different brain regions.

Neural interactions occur on different levels and scales. It is of particular importance to understand how they are distributed among different neuroanatomical and physiological relevant brain regions. We investigated neural cross-frequency couplings between different brain regions according to the Desikan-Killiany brain parcellation. The adaptive dynamic Bayesian inference method was applied to EEG measurements of healthy resting subjects in order to reconstruct the coupling functions. It was found that even after averaging over all subjects, the mean coupling function showed a characteristic waveform, confirming the direct influence of the delta-phase on the alpha-phase dynamics in certain brain regions and that the shape of the coupling function changes for different regions. While the averaged coupling function within a region was of similar form, the region-averaged coupling function was averaged out, which implies that there is a common dependence within separate regions across the subjects. It was also found that for certain regions the influence of delta on alpha oscillations is more pronounced and that oscillations that influence other are more evenly distributed across brain regions than the influenced oscillations. When presenting the information on brain lobes, it was shown that the influence of delta emanating from the brain as a whole is greatest on the alpha oscillations of the cingulate frontal lobe, and at the same time the influence of delta from the cingulate parietal brain lobe is greatest on the alpha oscillations of the whole brain.

A Human Neuron/Astrocyte Co-culture to Model Seeded and Spontaneous Intraneuronal Tau Aggregation.

Communication and contact between neurons and astrocytes is important for proper brain physiology. How neuron/astrocyte crosstalk is affected by intraneuronal tau aggregation in neurodegenerative tauopathies is largely elusive. Human induced pluripotent stem cell (iPSC)-derived neurons provide the opportunity to model tau pathology in a translationally relevant in vitro context. However, current iPSC models inefficiently develop tau aggregates, and co-culture models of tau pathology have thus far utilized rodent astrocytes. In this article, we describe the co-culture of human iPSC-derived neurons with primary human astrocytes in a 96-well format compatible with high-content microscopy. By lentiviral overexpression of different mutated tau variants, this protocol can be flexibly adapted for the efficient induction of seeded or spontaneous tau aggregation. We used this novel co-culture model to identify cell type-specific disease mechanisms and to provide proof of concept for intervention by antisense therapy. These results show that this human co-culture model provides a highly translational tool for target discovery and drug development for human tauopathies. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Human neuron/astrocyte co-culture for seeded and spontaneous intraneuronal tau aggregation Support Protocol 1: Human induced pluripotent stem cell culture Support Protocol 2: Human primary astrocyte culture.

Negative environmental influences on the developing brain mediated by epigenetic modifications

Brain development, a complex process, consisting of several phases, starting as early as two weeks after conception, and continuing through childhood till early adolescence, is crucial for the development of properly functioning body systems, behavioral traits, and neurocognitive abilities. Infancy and childhood are recognized as important periods for initial brain formation, however in later stages of life, such as childhood and adulthood, experiences, together with environmental exposures, can still influence brain physiology. The developing brain is particularly susceptible to epigenetic changes with many factors being proposed as modifiers by directly impacting DNA methylation as well as histone and chromatin modifications within genes implicated in development. These factors include: maternal stress and diet, exposure to pollutants, sleep quality, as well as dietary habits. Evidence indicates exposures to environmental threats can lead to inappropriate neurological, metabolic, and endocrine functioning often mediated by epigenetic mechanisms with symptoms manifesting themselves as early as childhood or in later stages of life. Therefore, the main aim of this review is to evaluate the current studies focused on negative environmental exposures and their consequences on the developing brain directed by epigenetic mechanisms.

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry.

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly.

An Update on Role of Bile Acids in Neurological Functions and Neurodegenerative Diseases: A Narrative Review

Having previously reviewed the role of Bile Acids (BAs) in obesity, NAFLD/NASH/HCC and crosstalk of Gut Microbiome in numerous body disorders here we further attempted to assess part of BAs in normal brain physiology and in different Neurodegenerative Diseases (NDD). BAs constitute significant physiological molecules which apart from modulating nutrient absorption as well as metabolism in peripheral tissues influence neuromodulatory actions in the Central Nervous System (CNS). The formation of bile acids takes place basically from cholesterol in the liver by the canonical as well as alternate pathwaysor in the brain started by the neuron particular sterol Cholesterol-24 hydroxylase (CYP46A1) modulated pathway. Circulating BAs possess the capacity of crossing the Blood Brain Barrier (BBB) and thus gaining entry into the CNS via passive diffusion or through BAs transporters. Brain BAs act in the CNS via activation of membrane or nuclear receptors or influence the working of the neurotransmitter receptors. Indirect signal might be further given to the CNS through the Farsenoid X Receptor (FXR) based Fibroblast growth factor 15/19 (FGF15/19) pathway or the takeda G Protein Coupled (GPC) bile acid receptor 5 (TGR5) based Glucagon Like Peptide 1(GLP) pathway. In case of pathological situations, changes in BAs have been observed to probably aid in the pathogenesis of different neurological diseases. Of greater significance is the supplementationof hydrophilic amidated Ursodeoxycholic Acid (UDCA) or Tauroursodeoxycholic Acid (TUDCA) have been corroborated to illustrate therapeutic advantagesby hampering the neuroinflammatory reactions, apoptosis, Oxidative Stress (OS), Endoplasmic Reticulum (ER) stress, mitochondrial protection or work in the form of probable chaperone for correction of misfolding of proteins in the treatment of different neurological diseases. This yields opportunity of utilization of UDCA along with TUDCA in the treatment of different neurodegenerative diseases inclusive of Alzheimer’s disease; Parkinson’s disease, Huntingtons disease, Amyotrophic Lateral sclerosis, and prion disease.

Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning.

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived "find-me," "eat-me," and "don't eat-me" molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

Can we model autism using zebrafish?

Autism spectrum disorder (ASD) is one of the most common, heritable neuropsychiatric disorders in the world, affecting almost 1% of the population. The core symptoms used to diagnose ASD are decreased social interaction and increased repetitive behaviors. Despite the large number of affected individuals, the precise mechanisms that cause this disorder remain unclear. The identification of genes and environmental factors associated with ASD allows the study of the underlying mechanisms in animal models. Although ASD presents as a human disorder, based on recent advances in understanding their brain anatomy, physiology, behavior, and evolutionary conservation of neuronal cell types, I propose that zebrafish may provide novel insights into the etiology.

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

BackgroundExcessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function. MethodsEleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (Tre) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (Tbr), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques. ResultsTbr in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in Tre. With the development of hyperthermia, Tbr increases and dovetails with the rising Tre. Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (Tre = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both Tre and Tbr and mitigated heat-related neural perturbations. ConclusionSevere heat exposure elevates Tbr, disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance.

Assessment of factors influencing glymphatic activity and implications for clinical medicine.

The glymphatic system is a highly specialized fluid transport system in the central nervous system. It enables the exchange of the intercellular fluid of the brain, regulation of the movement of this fluid, clearance of unnecessary metabolic products, and, potentially, brain immunity. In this review, based on the latest scientific reports, we present the mechanism of action and function of the glymphatic system and look at the role of factors influencing its activity. Sleep habits, eating patterns, coexisting stress or hypertension, and physical activity can significantly affect glymphatic activity. Modifying them can help to change lives for the better. In the next section of the review, we discuss the connection between the glymphatic system and neurological disorders. Its association with many disease entities suggests that it plays a major role in the physiology of the whole brain, linking many pathophysiological pathways of individual diseases.

Gut microbiome association with brain imaging markers, APOE genotype, calcium and vegetable intakes, and obesity in healthy aging adults.

Advanced age is a significant factor in changes to brain physiology and cognitive functions. Recent research has highlighted the critical role of the gut microbiome in modulating brain functions during aging, which can be influenced by various factors such as apolipoprotein E (APOE) genetic variance, body mass index (BMI), diabetes, and dietary intake. However, the associations between the gut microbiome and these factors, as well as brain structural, vascular, and metabolic imaging markers, have not been well explored. We recruited 30 community dwelling older adults between age 55-85 in Kentucky. We collected the medical history from the electronic health record as well as the Dietary Screener Questionnaire. We performed APOE genotyping with an oral swab, gut microbiome analysis using metagenomics sequencing, and brain structural, vascular, and metabolic imaging using MRI. Individuals with APOE e2 and APOE e4 genotypes had distinct microbiota composition, and higher level of pro-inflammatory microbiota were associated higher BMI and diabetes. In contrast, calcium- and vegetable-rich diets were associated with microbiota that produced short chain fatty acids leading to an anti-inflammatory state. We also found that important gut microbial butyrate producers were correlated with the volume of the thalamus and corpus callosum, which are regions of the brain responsible for relaying and processing information. Additionally, putative proinflammatory species were negatively correlated with GABA production, an inhibitory neurotransmitter. Furthermore, we observed that the relative abundance of bacteria from the family Eggerthellaceae, equol producers, was correlated with white matter integrity in tracts connecting the brain regions related to language, memory, and learning. These findings highlight the importance of gut microbiome association with brain health in aging population and could have important implications aimed at optimizing healthy brain aging through precision prebiotic, probiotic or dietary interventions.