J. Neurosci. Res. [JOURNAL]
Sun
200 papers
CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity.
Melrose J
J Neurosci Res · 2024 Jul · PMID 39034899 · Publisher ↗
Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a...
Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space-filling, cell supportive, stabilizing structure maintaining tissue compartments, ionic microenvironments, and microgradients that regulate neuronal activity and maintain the neuron in an optimal ionic microenvironment. The CNS/PNS contains a high glycosaminoglycan content (60% hyaluronan, HA) and a diverse range of stabilizing PGs. Immobilization of HA in brain tissues by HA interactive hyalectan PGs preserves tissue hydration and neuronal activity, a paucity of HA in brain tissues results in a pro-convulsant epileptic phenotype. Diverse CS, KS, and HSPGs stabilize the blood-brain barrier and neurovascular unit, provide smart gel neurotransmitter neuron vesicle storage and delivery, organize the neuromuscular junction basement membrane, and provide motor neuron synaptic plasticity, and photoreceptor and neuron synaptic functions. PG-HA networks maintain ionic fluxes and microgradients and tissue compartments that contribute to membrane polarization dynamics essential to neuronal activation and neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing to synaptic plasticity, memory, and cognitive learning. Sialoglycoprotein associated with cones and rods (SPACRCAN), an HA binding CSPG, stabilizes the inter-photoreceptor ECM. HSPGs pikachurin and eyes shut stabilize the photoreceptor synapse aiding in phototransduction and neurotransduction with retinal bipolar neurons crucial to visual acuity. This is achieved through Laminin G motifs in pikachurin, eyes shut, and neurexins that interact with the dystroglycan-cytoskeleton-ECM-stabilizing synaptic interconnections, neuronal interactive specificity, and co-ordination of regulatory action potentials in neural networks.
Investigating social communication in mice: A two-intruders test approach.
Morozova MV, Boldyreva LV, Borisova MA … +1 more , Kozhevnikova EN
J Neurosci Res · 2024 Jul · PMID 39031484 · Publisher ↗
Understanding the complex dynamics of social communication behaviors, such as exploration, communication, courtship, mating, and aggression in animal models, is crucial to reveal key neural and hormonal mechanisms underl...
Understanding the complex dynamics of social communication behaviors, such as exploration, communication, courtship, mating, and aggression in animal models, is crucial to reveal key neural and hormonal mechanisms underlying these behaviors. The two-intruders test is designed to investigate residents' behavior toward both male and female intruders within the home cage of the test male. During this test imitating natural conditions, several aspects of social interaction were investigated: Exploration, courtship, mating, and aggressive behavior. As mating and aggression involve overlapping neural circuits, the behavioral setup testing both behaviors is best at reflecting their competitive nature. Our findings demonstrate that resident male mice exhibit strong preference to communicate with a female intruder, which correlates with baseline testosterone levels of test males. Relevant female preference in the two-intruders test was also found in BALB/c males. Behavioral breakdown revealed the anogenital sniffing as a key behavioral feature that discriminates resident male behavior toward intruders of different sex. Furthermore, resident male interaction with female intruder was accompanied by neuronal activation in the ventromedial hypothalamus. We demonstrate that odor recognition underlies preference toward females in male residents, as experimental anosmia reduced communication with a female intruder. We conclude the two-intruders test setup to be a useful tool to study the neurological basis of social communication in animal models, which provides detailed analysis of various aspects of the laboratory animals' social behavior in the most natural conditions.
A systematic review of MRI studies on the effects of maternal obesity on offspring brain structure and function.
Parsaei M, Hashemi SM, Moghaddam HS … +1 more , Peterson BS
J Neurosci Res · 2024 Jul · PMID 39007363 · Publisher ↗
Maternal obesity before or during pregnancy has been associated previously in offspring with a wide range of poor neurodevelopmental outcomes and mental health problems. The effects of maternal obesity on offspring brain...
Maternal obesity before or during pregnancy has been associated previously in offspring with a wide range of poor neurodevelopmental outcomes and mental health problems. The effects of maternal obesity on offspring brain structure and function that may be responsible for these poor outcomes are not well understood. We, therefore, undertook a systematic review of magnetic resonance imaging (MRI) studies that have assessed the associations of maternal obesity with brain measures in offspring. A systematic search was conducted in PubMed, Web of Science, Scopus, and PsycINFO on August 20, 2023. Of 15 eligible studies, seven employed functional MRI (fMRI), five diffusion tensor imaging (DTI), and four anatomical MRI (one used both DTI and anatomical MRI) in the offspring. The ages of offspring varied widely: one was a study of fetuses in utero, five of neonates, one of infants, five of school-aged children, two of both neonates and infants, and one of both children and adults. Collectively, 12 studies reported significant associations of maternal obesity with structural or functional alterations of the offspring's brain, most frequently in the prefrontal cortex and limbic system. In conclusion, maternal obesity appears to have a profound influence on offspring brain development, particularly within the prefrontal and limbic networks that regulate emotion and behavior. Further studies are needed to identify how changes in brain structure and function mediate the effects of maternal obesity on long-term emotional and behavioral outcomes, as well as the molecular pathways through which maternal obesity alters offspring brain development.
Restoration of sleep-wake behavior following short photoperiod exposure in ventral subicular lesioned male Wistar rats: A 24-h sleep-wake electroencephalographical study.
Prem N, Sasidharan A, Srikumar BN … +2 more , Rao BSS, Kutty BM
J Neurosci Res · 2024 Jul · PMID 39001670 · Publisher ↗
The ventral subiculum regulates emotion, stress responses, and spatial and social cognition. In our previous studies, we have demonstrated anxiety- and depression-like symptoms, deficits in spatial and social cognition i...
The ventral subiculum regulates emotion, stress responses, and spatial and social cognition. In our previous studies, we have demonstrated anxiety- and depression-like symptoms, deficits in spatial and social cognition in ventral subicular lesioned (VSL) rats, and restoration of affective and cognitive behaviors following photoperiod manipulation (short photoperiod regime, SPR; 6:18 LD cycle). In the present study, we have studied the impact of VSL on sleep-wake behavioral patterns and the effect of SPR on sleep-wakefulness behavior. Adult male Wistar rats subjected to VSL demonstrated decreased wake duration and enhanced total sleep time due to increased non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). Power spectral analysis indicated increased delta activity during NREMS and decreased sigma band power during all vigilance states. Light is one of the strongest entrainers of the circadian rhythm, and its manipulation may have various physiological and functional consequences. We investigated the effect of 21-day exposure to SPR on sleep-wakefulness (S-W) behavior in VSL rats. We observed that SPR exposure restored S-W behavior in VSL rats, resulting in an increase in wake duration and a significant increase in theta power during wake and REMS. This study highlights the crucial role of the ventral subiculum in maintaining normal sleep-wakefulness patterns and highlights the effectiveness of photoperiod manipulation as a non-pharmacological treatment for reversing sleep disturbances reported in mood and neuropsychiatric disorders like Alzheimer's disease, bipolar disorder, and major depressive disorder, which also involve alterations in circadian rhythm.
A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury.
Smith AM, Grayson BE
J Neurosci Res · 2024 Jul · PMID 38953607 · Publisher ↗
Traumatic brain injury (TBI) is a condition that occurs commonly in children from infancy through adolescence and is a global health concern. Pediatric TBI presents with a bimodal age distribution, with very young childr...
Traumatic brain injury (TBI) is a condition that occurs commonly in children from infancy through adolescence and is a global health concern. Pediatric TBI presents with a bimodal age distribution, with very young children (0-4 years) and adolescents (15-19 years) more commonly injured. Because children's brains are still developing, there is increased vulnerability to the effects of head trauma, which results in entirely different patterns of injury than in adults. Pediatric TBI has a profound and lasting impact on a child's development and quality of life, resulting in long-lasting consequences to physical, cognitive, and emotional development. Chronic issues like learning disabilities, behavioral problems, and emotional disturbances can develop. Early intervention and ongoing support are critical for minimizing these long-term deficits. Many animal models of TBI exist, and each varies significantly, displaying different characteristics of clinical TBI. The neurodevelopment differs in the rodent from the human in timing and effect, so TBI outcomes in the juvenile rodent can thus vary from the human child. The current review compares findings from preclinical TBI work in juvenile and adult rodents to clinical TBI research in pediatric and adult humans. We focus on the four brain regions most affected by TBI: the prefrontal cortex, corpus callosum, hippocampus, and hypothalamus. Each has its unique developmental projections and thus is impacted by TBI differently. This review aims to compare the healthy neurodevelopment of these four brain regions in humans to the developmental processes in rodents.
Gray matter alterations in Huntington's disease: A meta-analysis of VBM neuroimaging studies.
Wang X, Li Y, Li B … +2 more , Shang H, Yang J
J Neurosci Res · 2024 Jul · PMID 38953592 · Publisher ↗
Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate t...
Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.
Newborn auditory brainstem response and sudden infant death syndrome.
Maylott SE, Zeng G, Leung TS … +6 more , Montenegro CS, Barrios A, Malik A, Delgado RE, Delgado CF, Simpson EA
J Neurosci Res · 2024 Jun · PMID 38895852 · Publisher ↗
Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep....
Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.
Temporal summation of second pain is affected by cognitive load.
Rubal-Otero L, Gil-Ugidos A, Villar AJG … +1 more , Carrillo-de-la-Peña MT
J Neurosci Res · 2024 Jun · PMID 38895850 · Publisher ↗
This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtain...
This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.
Progresses in the establishment, evaluation, and application of in vitro blood-brain barrier models.
Yin P, Wang X
J Neurosci Res · 2024 Jun · PMID 38859680 · Publisher ↗
The blood-brain barrier (BBB) is a barrier between the circulatory system and the central nervous system (CNS), contributing to CNS protection and maintaining the brain homeostasis. Establishment of in vitro BBB models t...
The blood-brain barrier (BBB) is a barrier between the circulatory system and the central nervous system (CNS), contributing to CNS protection and maintaining the brain homeostasis. Establishment of in vitro BBB models that are closer to the microenvironment of the human brain is helpful for evaluating the potential and efficiency of a drug penetrating BBB and thus the clinical application value of the drug. The in vitro BBB models not only provide great convenience for screening new drugs that can access to CNS but also help people to have a deeper study on the mechanism of substances entering and leaving the brain, which makes people have greater opportunities in the treatment of CNS diseases. Up to now, although much effort has been paid to the researches on the in vitro BBB models and many progresses have been achieved, no unified method has been described for establishing a BBB model and there is much work to do and many challenges to be faced with in the future. This review summarizes the research progresses in the establishment, evaluation, and application of in vitro BBB models.
Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke.
Peipei W, Yu D, Xiaoyan L … +4 more , Yunxia L, Liuming L, Tongbin C, Shaoping L
J Neurosci Res · 2024 Jun · PMID 38859672 · Publisher ↗
Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has...
Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has recently been reported to regulate microglial functions and exert anti-inflammatory effects. The intermittent burst stimulation (iTBS) regimen in rTMS improves neuronal excitability. However, whether iTBS exerts its anti-inflammatory effects by stimulating neurons and thereby modulating microglial polarization remains unclear. Motor function was assessed after 1 week of rTMS (iTBS regimen) treatment in adult male mice with occlusion/reperfusion of the middle cerebral artery (MCAO/r) injury. We also investigated the molecular biological alterations associated with microglial polarization using a cell proliferation assay, multiplex cytokine bioassays, and immunofluorescence staining. iTBS regimen can improve balance and motor coordination function, increase spontaneous movement, and improve walking function in mice with early cerebral ischemia injury. Expression levels of IL-1β, TNF-α, and IL-10 increased significantly in mice with MCAO injury. Especially, rTMS significantly increased the number of proliferating cells in the infarcted cortex. The fluorescence intensity of MAP2 in the peri-infarct area of MCAO injured mice was low, but the signal was broader. Compared with MCAO group, the fluorescence intensity of MAP2 in rTMS group was significantly increased. rTMS inhibited pro-inflammatory M1 activation (Iba1/CD86) and improved anti-inflammatory M2 activation (Iba1/CD206) in the peri-infarct zone, thus significantly changing the phenotypic ratio M1/M2. rTMS improves motor dysfunction and neuroinflammation after cerebral I/R injury in mice by regulating microglial polarization.
Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.
Osorio-Gómez D, Perez CI, Salcedo-Tello P … +8 more , Hernández-Matias A, Hernández-Ramírez S, Arroyo B, Pacheco-López G, Gutierrez R, Bermúdez-Rattoni F, Guzmán-Ramos K, OBETEEN Consortium
J Neurosci Res · 2024 Jun · PMID 38847288 · Publisher ↗
Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and a...
Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.
GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia.
Nascimento AA, Pereira-Figueiredo D, Borges-Martins VP … +2 more , Kubrusly RC, Calaza KC
J Neurosci Res · 2024 May · PMID 38808645 · Publisher ↗
Gamma aminobutyric acid (GABA) is a critical inhibitory neurotransmitter in the central nervous system that plays a vital role in modulating neuronal excitability. Dysregulation of GABAergic signaling, particularly invol...
Gamma aminobutyric acid (GABA) is a critical inhibitory neurotransmitter in the central nervous system that plays a vital role in modulating neuronal excitability. Dysregulation of GABAergic signaling, particularly involving the cotransporters NKCC1 and KCC2, has been implicated in various pathologies, including epilepsy, schizophrenia, autism spectrum disorder, Down syndrome, and ischemia. NKCC1 facilitates chloride influx, whereas KCC2 mediates chloride efflux via potassium gradient. Altered expression and function of these cotransporters have been associated with excitotoxicity, inflammation, and cellular death in ischemic events characterized by reduced cerebral blood flow, leading to compromised tissue metabolism and subsequent cell death. NKCC1 inhibition has emerged as a potential therapeutic approach to attenuate intracellular chloride accumulation and mitigate neuronal damage during ischemic events. Similarly, targeting KCC2, which regulates chloride efflux, holds promise for improving outcomes and reducing neuronal damage under ischemic conditions. This review emphasizes the critical roles of GABA, NKCC1, and KCC2 in ischemic pathologies and their potential as therapeutic targets. Inhibiting or modulating the activity of these cotransporters represents a promising strategy for reducing neuronal damage, preventing excitotoxicity, and improving neurological outcomes following ischemic events. Furthermore, exploring the interactions between natural compounds and NKCC1/KCC2 provides additional avenues for potential therapeutic interventions for ischemic injury.
The influence of accelerated brain aging on coactivation pattern dynamics in Parkinson's disease.
Yan S, Lu J, Zhu H … +4 more , Tian T, Qin Y, Li Y, Zhu W
J Neurosci Res · 2024 May · PMID 38803227 · Publisher ↗
Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging o...
Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large-scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G-brainAGE and L-brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting-state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L-brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (-3.73 years), G-brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L-brainAGE. G-brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto-parietal network (DMN-FPN), as well as the sensorimotor and salience network (SMN-SN), and had a reduced transition frequency from other CAPs to the DMN-FPN and SMN-SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN-SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.
The interplay between glucose and ketone bodies in neural stem cell metabolism.
Molloy JW, Barry D
J Neurosci Res · 2024 May · PMID 38773878 · Publisher ↗
Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply,...
Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply, leading to the utilization of alternative energy sources including ketone bodies. Ketone bodies, including β-hydroxybutyrate, are short-chain fatty acids produced through hepatic ketogenesis and play a crucial role in providing energy and the biosynthetic components for NSCs when required. The interplay between glucose and ketone metabolism influences NSC behavior and fate decisions, and disruptions in these metabolic pathways have been linked to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Additionally, ketone bodies exert neuroprotective effects on NSCs and modulate cellular responses to oxidative stress, energy maintenance, deacetylation, and inflammation. As such, understanding the interdependence of glucose and ketone metabolism in NSCs is crucial to understanding their roles in NSC function and their implications for neurological conditions. This article reviews the mechanisms of glucose and ketone utilization in NSCs, their impact on NSC function, and the therapeutic potential of targeting these metabolic pathways in neurological disorders.
Heterogeneity of brain extracellular matrix and astrocyte activation.
Huber RE, Babbitt C, Peyton SR
J Neurosci Res · 2024 May · PMID 38773875 · Publisher ↗
From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes...
From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes and functions varying both regionally and temporally. Astrocytes' metabolic and regulatory functions poise them to be quick and sensitive responders to injury and disease in the brain as revealed by single cell sequencing. Far less is known about the influence of the local healthy and aging microenvironments on these astrocyte activation states. In this forward-looking review, we describe the known relationship between astrocytes and their local microenvironment, the remodeling of the microenvironment during disease and injury, and postulate how they may drive astrocyte activation. We suggest technology development to better understand the dynamic diversity of astrocyte activation states, and how basal and activation states depend on the ECM microenvironment. A deeper understanding of astrocyte response to stimuli in ECM-specific contexts (brain region, age, and sex of individual), paves the way to revolutionize how the field considers astrocyte-ECM interactions in brain injury and disease and opens routes to return astrocytes to a healthy quiescent state.
Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups.
Del Mauro G, Sevel LS, Boissoneault J … +1 more , Wang Z
J Neurosci Res · 2024 May · PMID 38751218 · Full text
Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to invest...
Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to investigate the neural correlates of pain experience. BEN was estimated from rs-fMRI data provided by two datasets with different age range: the Human Connectome Project-Young Adult (HCP-YA) and the Human Connectome project-Aging (HCP-A) datasets. Retrospective assessment of experienced pain intensity was retrieved from both datasets. No main effect of pain intensity was observed. The interaction between pain and age, however, was related to increased BEN in several pain-related brain regions, reflecting greater variability of spontaneous brain activity. Dividing the sample into a young adult group (YG) and a middle age-aging group (MAG) resulted in two divergent patterns of pain-BEN association: In the YG, pain intensity was related to reduced BEN in brain regions involved in the sensory processing of pain; in the MAG, pain was associated with increased BEN in areas related to both sensory and cognitive aspects of pain experience.
Implications of environmental nanoparticles on neurodegeneration.
Hermosillo-Abundis C, Méndez-Rojas MA, Arias-Carrión O
J Neurosci Res · 2024 May · PMID 38745527 · Publisher ↗
The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications-espe...
The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications-especially in enhancing drug transport across the blood-brain barrier-these particles also introduce possible hazards due to inadvertent exposure. This concise review explores the paradoxical nature of nanoparticles, emphasizing their promising applications in healthcare juxtaposed with their potential neurotoxic consequences. Through a detailed examination, we delineate the pathways through which nanoparticles can reach the brain and the subsequent health implications. There is growing evidence of a disturbing association between nanoparticle exposure and the onset of neurodegenerative conditions, highlighting the imperative for comprehensive research and strategic interventions. Gaining a deep understanding of these mechanisms and enacting protective policies are crucial steps toward reducing the health threats of nanoparticles, thereby maximizing their therapeutic advantages.
The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice.
Collado-Perez R, Chamoso-Sánchez D, García A … +6 more , Fernández-Alfonso MS, Jiménez-Hernáiz M, Canelles S, Argente J, Frago LM, Chowen JA
J Neurosci Res · 2024 May · PMID 38741550 · Publisher ↗
Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to...
Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid β-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.
IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats.
Sadek M, Stover KR, Liu X … +3 more , Reed MA, Weaver DF, Reid AY
J Neurosci Res · 2024 May · PMID 38706427 · Publisher ↗
The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a resu...
The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production of IDO1 and boost its enzymatic capacity. IDO1 and the KP have been implicated in behavioral recovery after human traumatic brain injury (TBI), but their roles in experimental models of TBI are for the most part unknown. We hypothesized there is an increase in KP activity in the fluid percussion injury (FPI) model of TBI, and that administration of an IDO1 inhibitor will improve neurological recovery. In this study, adult male Sprague Dawley rats were subjected to FPI or sham injury and received twice-daily oral administration of the IDO1 inhibitor PF-06840003 (100 mg/kg) or vehicle control. FPI resulted in a significant increase in KP activity, as demonstrated by an increased ratio of kynurenine: tryptophan, in the perilesional neocortex and ipsilateral hippocampus 3 days postinjury (DPI), which normalized by 7 DPI. The increase in KP activity was prevented by PF-06840003. IDO1 inhibition also improved memory performance as assessed in the Barnes maze and anxiety behaviors as assessed in open field testing in the first 28 DPI. These results suggest increased KP activity after FPI may mediate neurological dysfunction, and IDO1 inhibition should be further investigated as a potential therapeutic target to improve recovery.
Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease.
Tamnanloo F, Chen X, Oliveira MM … +2 more , Tremblay M, Rose CF
J Neurosci Res · 2024 May · PMID 38680084 · Publisher ↗
Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented...
Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated the impact of excessive alcohol administration on neurological deterioration in rats with CLD. Starting day 7 post-BDL surgery, rats were administered alcohol twice daily (51% v/v ethanol, 3 g/kg, via gavage) for 4 weeks. Motor coordination was assessed weekly using rotarod and anxiety-like behavior was evaluated with open field and elevated plus maze at 5 weeks. Upon sacrifice, brains were collected for western blot and immunohistochemical analyses to investigate neuronal integrity and oxidative stress status. Alcohol worsened motor coordination performance and increased anxiety-like behavior in BDL rats. Impairments were associated with decreased neuronal markers of NeuN and SMI311, increased apoptotic markers of cleaved/pro-caspase-3 and Bax/Bcl2, increased necroptosis markers of pRIP3 and pMLKL, decreased total antioxidant capacity (TAC), and increased 4-hydroxynonenal (4-HNE)modified proteins in the cerebellum of BDL-alcohol rats when compared to respective controls. Immunofluorescence confirmed the colocalization of cleaved caspase-3 and pMLKL in the granular neurons of the cerebellum of BDL-alcohol rats. Excessive alcohol consumption exacerbates HE which leads to associated apoptotic and necroptotic neuronal loss in the cerebellum of BDL-alcohol rats. Additionally, higher levels of 4-HNE and decreased TAC in the cerebellum of BDL-alcohol rats suggest oxidative stress is the triggering factor of apoptotic and necroptotic neuronal loss/injury.
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