J. Neurosci. Res. [JOURNAL]
Sun
200 papers
Transcription Factors and Coregulators in Schwann Cell Differentiation, Myelination, and Remyelination: Implications for Peripheral Neuropathy.
Han SH, Cho JG, Park SJ … +5 more , Shin YK, Hong YB, Han JY, Park HT, Park JI
J Neurosci Res · 2025 Jun · PMID 40452391 · Publisher ↗
Schwann cells (SCs) are required for supporting axons, forming myelin, and facilitating repair through remyelination after injury in the peripheral nervous system (PNS). Processes of differentiation, myelination, and rem...
Schwann cells (SCs) are required for supporting axons, forming myelin, and facilitating repair through remyelination after injury in the peripheral nervous system (PNS). Processes of differentiation, myelination, and remyelination of SCs are tightly modulated by a complex network of transcription factors and coregulators, including Sox10, Oct6/Pou3f1, Krox20/Egr2, Nab1/2, YY1, COUP-TFII/NR2F2, YAP/TAZ-TEAD1, c-Jun, Sox2, Zeb2, and Etv1/Er81. These factors can regulate the expression of essential target genes such as Mpz and Mbp in SC myelination and repair. Genetic mutations or dysregulation within this network can lead to peripheral neuropathies such as Charcot-Marie-Tooth disease. However, the transcriptional regulatory network of differentiation, myelination, and remyelination of SCs has not been fully understood yet. Thus, this review briefly introduces processes of differentiation, myelination, and remyelination of SCs and explores the role and molecular mechanisms of each transcription factor and coregulator in differentiation and myelination of SCs and their remyelination following nerve injury. Clinical implications for peripheral neuropathies associated with specific gene mutations and variations of transcription factors and coregulators affecting SC biology are also discussed.
Astrocytic HSP60 Deletion Induced Astrocyte Senescence and Inhibited Neuroregeneration via Modulating the S1P/Truncated-BDNF Pathway.
Zhu W, Cheng Y, Lang Z … +2 more , Li W, Wei X
J Neurosci Res · 2025 Jun · PMID 40448367 · Publisher ↗
Heat Shock Protein 60 (HSP60) plays a critical role in maintaining mitochondrial function in astrocytes and has a significant impact on central nervous system (CNS) health. However, how HSP60 regulates the mitochondrial...
Heat Shock Protein 60 (HSP60) plays a critical role in maintaining mitochondrial function in astrocytes and has a significant impact on central nervous system (CNS) health. However, how HSP60 regulates the mitochondrial function of astrocytes to inhibit neuroregeneration remains unknown. In this study, we generated astrocyte-specific HSP60 knockout male mice to investigate the consequences of HSP60 deficiency. Firstly, our results confirmed that HSP60 deficiency caused abnormal expression of mitochondrial function-related genes, causing significant mitochondrial dysfunction, which triggered cellular senescence in astrocytes. Moreover, the alterations of 5-hydroxytryptamine 2A receptor (5-HT2AR), glucocorticoid receptor (GR), dopamine D2 receptor (D2R), and N-methyl-D-aspartate receptor subunit 2A (NR2A) expression suggested a disruption in neurotransmission and synaptic plasticity. Additionally, the increased levels of site-1 protease (S1P), truncated brain-derived neurotrophic factor (truncated-BDNF), and synaptophysin indicate synaptic structural and functional impairments. Expectedly, our findings demonstrated mitochondrial dysfunction and cellular senescence in astrocytes, leading to altered expression of neurotransmitter receptors in the cortex, as well as reduced neuronal numbers and neurotransmitter levels in the hippocampus after the deletion of HSP60 in astrocytes of the male mice. Notably, Urolithin A (UA) and the S1P inhibitor, PF429242, were found to alleviate astrocyte senescence and promote neuronal regeneration by inhibiting truncated BDNF expression. In conclusion, our study revealed that HSP60 deficiency in astrocytes induces mitochondrial dysfunction and cellular senescence via the S1P/truncated-BDNF pathway, resulting in disrupted neurotransmitter receptor expression, synaptic protein alterations, and impaired neuroregeneration. These insights underscored the importance of HSP60 in CNS health and provided promising avenues for developing treatments for neurodegenerative disorders.
Intermittent Hypoxia Damages Tyrosine Hydroxylase-Containing Neurons in the Substantia Nigra and Locus Coeruleus but Not Hippocampal Neurons in Male Mouse Models of Early-Stage Sleep Apnea.
Chu CH, Chang YC, Liu KT … +6 more , Liu YC, Chou MC, Liu CK, Chen CH, Chang JL, Chen SL
J Neurosci Res · 2025 Jun · PMID 40444532 · Publisher ↗
In sleep apnea, repeated hypovolemic ventilation or apnea in sleep leads to intermittent hypoxia (IH) of the brain. Thus, the impacts of sleep apnea on the brain need to be investigated. In this study, a mouse model with...
In sleep apnea, repeated hypovolemic ventilation or apnea in sleep leads to intermittent hypoxia (IH) of the brain. Thus, the impacts of sleep apnea on the brain need to be investigated. In this study, a mouse model with sleep-associated chronic IH and behavior tests was used to evaluate how IH impacts brain function and the expression of tyrosine hydroxylase (TH)-containing neurons in the substantia nigra, ventral tegmental area (VTA), and locus coeruleus. In an open-field test, mice subjected to chronic IH (5%-21% oxygen) for 10 and 20 days exhibited a significant decrease in spontaneous locomotor activity compared to the room air (RA, 21% oxygen) control mice. In the Y-maze test, the ability to recognize novel and familiar arms was similar between groups. In immunostaining of the brains of IH mice, TH-positive neurons in the substantia nigra, VTA, and locus coeruleus were significantly reduced compared to RA mice. Furthermore, in the brains of mice with decreased TH-positive neurons induced by IH, the expression of hippocampal neurons has not been affected. In the analysis of glial cells, in IH group mice, a significant increase of microglia was found in the substantia nigra, VTA, locus coeruleus, and hippocampus compared to the RA mice. These findings suggest that there is a loss of TH-containing neurons and neuronal inflammation in the substantia nigra, VTA, and locus coeruleus under chronic IH. Our findings provide precise evidence for the loss of TH-containing neurons in the setting of chronic IH mouse models, which can provide relevant empirical observations for clinicians.
Modeling Stress-Related Disorders in Zebrafish Using Prolonged Predator Exposure and Prolonged Unpredictable Stress.
Zhdanov AV, Khatsko SL, Zabegalov KN … +6 more , Bytov MV, Demin KA, Galstyan DS, de Abreu MS, Amstislavskaya TG, Kalueff AV
J Neurosci Res · 2025 Jun · PMID 40443120 · Publisher ↗
The neurobiology of human stress-related disorders remains poorly understood, necessitating novel models and new model organisms to advance translational research in this field. Complementing rodent studies, the zebrafis...
The neurobiology of human stress-related disorders remains poorly understood, necessitating novel models and new model organisms to advance translational research in this field. Complementing rodent studies, the zebrafish (Danio rerio) is a useful model species for stress-related disorders. Here, we develop two novel experimental models of stress-related brain disorders, based on repeated prolonged exposure to predators or on chronic unpredictable stress in adult zebrafish. The ability of both models to recapitulate human stress in these fish was assessed behaviorally, in the novel tank and the plus maze (anxiety, locomotor, and cognitive tests), as well as by analyzing the baseline levels of cortisol, a common neuroendocrine biomarker of stress. Overall, anxiety-like behavior in the novel tank test was seen in both stressed groups, whereas poor learning and higher anxiety were observed in the plus maze test in predator-exposed fish, paralleling clinical cognitive and affective symptoms. Elevated cortisol in both stressed zebrafish further resembled neuroendocrine deficits seen in stress-related disorders clinically. Finally, the evoked behavioral and endocrine stress symptoms were rescued by treatment with two popular, clinically active antidepressant drugs, fluoxetine and paroxetine. Collectively, these models successfully recapitulated in zebrafish several key aspects of clinical stress-related disorders, further supporting the utility of these fish for translational stress research and anti-stress drug development.
Resting-State Brain Amplitude of Low-Frequency Fluctuations: A Comparative Study Across Different Frequency Bands in Student Pilots.
Ye L, Yu X, Yan D … +1 more , Ma S
J Neurosci Res · 2025 May · PMID 40400335 · Publisher ↗
In this study, we aimed to investigate changes in the mean amplitude of low-frequency fluctuations (mALFF) in different frequency bands in flight trainees using resting-state functional magnetic resonance imaging (rs-fMR...
In this study, we aimed to investigate changes in the mean amplitude of low-frequency fluctuations (mALFF) in different frequency bands in flight trainees using resting-state functional magnetic resonance imaging (rs-fMRI) technology to explore the impact of flight training on brain functional changes. The study included 39 flight trainees and 37 well-matched healthy controls. MATLAB software was used to perform two-sample t-tests on the mALFF values of the subjects in different frequency bands to identify intergroup differences. SPSS software was used to perform correlation analysis between the different brain areas and the results of the Berg Card Sorting Test (BCST). The results revealed significant differences in mALFF values in multiple brain areas, including the left medial superior frontal gyrus and the left postcentral gyrus, between the two groups. Sub-bands revealed more differential brain areas compared to the classical band, and these differential brain areas were significantly correlated with the total accuracy of the BCST. Under resting conditions, flight trainees who underwent flight training showed significant differences from the control group in brain regions related to cognitive executive control, somatosensory function, memory function, and other functions. This may be related to the learning of critical flight skills, such as emergency operations, maneuvering the aircraft for takeoff, landing, and re-flight during executive flight training. Meanwhile, the sub-band is more sensitive to information about brain functional activities than the classical band, which provides a new perspective for further exploring the changes in pilot brain functional mechanisms in the future.
Effect of Anesthesia and Diurnal Variation on Chronic Vagus Nerve Activity in Rats.
Rodrigues AJ, Marmerstein JT, Kotamraju BP … +2 more , McCallum GA, Durand DM
J Neurosci Res · 2025 May · PMID 40391824 · Full text
The vagus nerve, serving as a pivotal link between the brain and vital organs, regulates crucial physiological functions. It plays a central role in maintaining homeostasis within the body and must dynamically adapt to c...
The vagus nerve, serving as a pivotal link between the brain and vital organs, regulates crucial physiological functions. It plays a central role in maintaining homeostasis within the body and must dynamically adapt to changing conditions such as anesthesia or sleep. While vagal tone, typically estimated indirectly from heart rate variability, has been extensively studied, direct measurement of vagal activity during sleep and anesthesia remains unreported to date. Recent technological advancements have facilitated the recording of vagus nerve activity in freely moving rodents using small, highly flexible carbon nanotube yarns. Consequently, it is now feasible to directly investigate vagal activity during events known to impact homeostasis, such as diurnal variations and anesthesia. In this study, we explore the relationship between anesthesia and vagus nerve activity by comparing the effects of 2% isoflurane anesthesia with activity in freely moving male Sprague Dawley rats. The findings reveal that 2% isoflurane anesthesia significantly suppresses vagus nerve activity, and normal activity levels do not resume until 2 h after the termination of the anesthesia supply. Additionally, we examine the influence of diurnal variations on vagus nerve activity and observe a notable presence of diurnal variations in vagal activity patterns. These results provide insights into the interaction among anesthesia, diurnal variations, and vagal tone, offering valuable understanding of the autonomic nervous system during critical physiological states.
Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.
Kelliny S, Zhou XF, Bobrovskaya L
J Neurosci Res · 2025 May · PMID 40387258 · Full text
Alzheimer's disease (AD) is a devastating form of dementia, with the number of affected individuals rising sharply. The main hallmarks of the disease include amyloid-beta plaque deposits and neurofibrillary tangles consi...
Alzheimer's disease (AD) is a devastating form of dementia, with the number of affected individuals rising sharply. The main hallmarks of the disease include amyloid-beta plaque deposits and neurofibrillary tangles consisting of hyperphosphorylated tau protein, besides other pathological features that contribute to the disease's complexity. The causes of sporadic AD are multifactorial and mostly age-related and involve risk factors such as diabetes and cardiovascular or cerebrovascular disorders. Frontotemporal dementia (FTD) is another type of dementia characterized by a spectrum of behaviors, memory, and motor abnormalities and associated with abnormal depositions of protein aggregation, including tau protein. Currently approved medications are symptomatic, and no disease-modifying therapy is available to halt the disease progression. Therefore, the development of multi-targeted therapeutic approaches could hold promise for the treatment of AD and other neurodegenerative disorders, including tauopathies. In this article, we will discuss the pathophysiology of AD and FTD, the proposed hypotheses, and current therapeutic approaches, highlighting the development of novel drug candidates and the progress of clinical trials in this field of research.
Modulation of GABAergic System in a Chicken Retinal Ischemic Model: The Role of Chloride Cotransporters.
Nascimento AA, Miya-Coreixas VS, Araújo DSM … +4 more , Nascimento THO, Santos GF, Brito R, Calaza KC
J Neurosci Res · 2025 May · PMID 40353346 · Full text
Retinal ischemia is a significant pathological condition that contributes to visual impairment and neuronal cell death in various retinopathies. Evidence suggests that GABA release during ischemic events may exhibit neur...
Retinal ischemia is a significant pathological condition that contributes to visual impairment and neuronal cell death in various retinopathies. Evidence suggests that GABA release during ischemic events may exhibit neuroprotective properties, but conflicting findings highlight a potential shift in its effects due to altered chloride ion homeostasis. This study aimed to investigate the role of the GABAergic system in retinal ischemia, focusing on the temporal dynamics of GABA release and its impact on retinal damage. We hypothesized that ischemia-induced changes in GABA transport and chloride ion equilibrium contribute to neuronal damage, which can be mitigated by modulating GABAergic activity. Using an ex vivo chick retina model subjected to oxygen and glucose deprivation (OGD), during different times, we assessed morphological changes, cell death, GABA levels, transporter activity, and the levels of chloride cotransporters NKCC1 and KCC2. Pharmacological interventions, including picrotoxin and bumetanide, were used to evaluate neuroprotective effects. Our results revealed that OGD-induced significant morphological changes and cell death in the retina. GABA levels were reduced in a GAT-1-dependent manner, while picrotoxin and bumetanide demonstrated neuroprotective effects by mitigating retinal swelling and modulating the GABAergic system. Notably, OGD increased NKCC1 content, but not KCC2 levels, indicating a disruption in chloride homeostasis. These findings suggest that ischemia-induced alterations in GABAergic activity and chloride transport contribute to retinal damage. Targeting these pathways with pharmacological agents, such as bumetanide, may offer therapeutic strategies for mitigating ischemic retinal injury. Further research is recommended to explore the clinical applicability of these findings in the ischemic retina.
Reduced Visual-Cortex Reorganization Before and After Cochlear Implantation Relates to Better Speech Recognition Ability.
Weglage A, Layer N, Radecke JO … +5 more , Meister H, Müller V, Lang-Roth R, Walger M, Sandmann P
J Neurosci Res · 2025 May · PMID 40342241 · Full text
Although a cochlear implant (CI) can partially restore auditory function, CI recipients show alterations not only in auditory but also in visual cortical processing. Yet, it is not well understood how these visual change...
Although a cochlear implant (CI) can partially restore auditory function, CI recipients show alterations not only in auditory but also in visual cortical processing. Yet, it is not well understood how these visual changes relate to the CI outcome and to what extent these changes are induced by auditory deprivation and the limited CI input, respectively. Here, we present a prospective longitudinal electroencephalography study which examined the deprivation- and CI-induced alterations on cortical face processing by comparing visual evoked potentials (VEP) in CI users before and 6 months after implantation. A group of normal-hearing (NH) listeners served as a control. The participants performed a word-identification task and a face-categorization task to study the cortical processing of static and articulating faces in attended and unattended conditions. The CI candidates and CI users showed a reduced visual-cortex activation, a stronger functional connectivity between the visual and auditory cortex, and a reduced attention effect in the (extended) alpha frequency range (8-18 Hz) when compared to NH listeners. There was a positive correlation between the P1 VEP amplitude recorded before implantation and the speech recognition ability after implantation. Our results suggest that the CI users' alterations in cortical face processing are mainly induced by auditory deprivation and not by CI experience. Importantly, these deprivation-induced changes seem to be related to the CI outcome. Our results suggest that the visual P1 amplitude as recorded before implantation provides an objective index of cortical visual reorganization that may help predict the CI outcome.
Tubulin Polymerization Promoting Proteins: Functional Diversity With Implications in Neurological Disorders.
Diaz PJ, Shi Q, McNeish PY … +1 more , Banerjee S
J Neurosci Res · 2025 May · PMID 40317801 · Full text
Tubulin Polymerization Promoting Proteins (TPPPs) are highly conserved across species but remain poorly understood. There are three TPPP genes in humans, with only one homologous TPPP gene in invertebrates, such as Droso...
Tubulin Polymerization Promoting Proteins (TPPPs) are highly conserved across species but remain poorly understood. There are three TPPP genes in humans, with only one homologous TPPP gene in invertebrates, such as Drosophila and C. elegans. The human TPPP (TPPP1/p25/p25α) is enriched in the brain and shares sequence similarities with the invertebrate TPPPs. TPPP/p25 associates with microtubules and plays a pivotal role in microtubule dynamics, bundling, and polymerization, thereby stabilizing the microtubular network. This is essential for cytoskeletal organization and proper functioning of neurons and glial cells, including axonal growth, regeneration, migration, trafficking, synapse formation, and myelination of axons. However, studies have also uncovered that besides its cytoplasmic/microtubular localization, TPPP/p25 is present in other subcellular compartments, including the mitochondria and nucleus, underscoring the presence of additional novel functions. At the molecular level, TPPP/p25 is predicted to exist as an intrinsically disordered protein and is implicated in neurological and neurodegenerative disorders, including Parkinson's and related disorders and Multiple Sclerosis. In this article, we provide a comprehensive overview of TPPP/p25, highlighting its evolutionary conservation, cellular and subcellular localization, established and emerging functions in the nervous system, interacting partners, potential clinical relevance to human neurological disorders, and conclude with unresolved questions and future areas of study.
A Novel HS Donor Alleviates Neuroinflammation and Seizures by Inhibiting the C3-C3aR Pathway.
Yang Y, Wang X, Wang T … +5 more , Wang X, Xu H, Liu L, Lei S, Zhu XQ
J Neurosci Res · 2025 May · PMID 40317781 · Publisher ↗
Both astrocytes and microglia are activated in the epileptic brain. There is an interaction between them through the complement 3 (C3)-C3a receptor (C3aR) pathway, which plays a detrimental role in seizures. Our self-dev...
Both astrocytes and microglia are activated in the epileptic brain. There is an interaction between them through the complement 3 (C3)-C3a receptor (C3aR) pathway, which plays a detrimental role in seizures. Our self-developed novel HS donor has been found to have anti-seizure effects. However, its mechanism remains to be explored. In the present study, we showed that the novel HS donor can inhibit the activation of astrocytes and microglia and their interaction through C3-C3aR signaling, which contributed to alleviating microglial neuroinflammation and seizures. In LPS-treated astrocytes and pilocarpine-induced epileptic mice, the HS donor reduced C3 production in astrocytes and regulated the expression of inflammatory cytokines IL-1β and IL-10 in microglia. The HS donor also reduced the EEG amplitude of hippocampal epileptic waves and relieved seizures in epileptic mice. These effects of the HS donor can be reversed by intranasal C3 treatment and mimicked by a C3aR antagonist. These findings provide a novel mechanism underlying the anti-seizure effects of the HS donor. Therefore, the HS donor has the potential to be used as a candidate for antiepileptic drugs.
A Novel Mutation in CNTNAP1 Gene Causes Disorganization of Axonal Domains, Hypomyelination and Severe Neurological Deficits.
Sell LB, Zabel C, Grønborg SW … +2 more , Shi Q, Bhat MA
J Neurosci Res · 2025 Apr · PMID 40265789 · Full text
CNTNAP1 encodes the contactin-associated protein 1 (Cntnap1) which localizes to the paranodal region in all myelinated axons and is essential for axonal domain organization and the propagation of action potentials. To da...
CNTNAP1 encodes the contactin-associated protein 1 (Cntnap1) which localizes to the paranodal region in all myelinated axons and is essential for axonal domain organization and the propagation of action potentials. To date, close to 45 reported human CNTNAP1 variants have been identified that are associated with dysregulation and disorganization of the axonal domains, resulting in various forms of congenital hypomyelinating neuropathies in children. Currently, no treatments are available for neuropathies caused by CNTNAP1 variants, highlighting the importance of fully characterizing these mutations and their impact on Cntnap1 functions. To understand the importance of a novel human CNTNAP1 likely pathogenic variant that changes glycine at position 349 to valine in a child who also carries a CNTNAP1 truncation and displayed severe neurological deficits, we used CRISPR/Cas9 methodology and introduced a single nucleotide substitution in the mouse Cntnap1 gene, resulting in glycine at 350 to valine (Cntnap1). Trans-allelic combination of Cntnap1 with a Cntnap1 null allele (Cntnap1) mimics human pathologies, recapitulating hypomyelination neuropathies associated with CNTNAP1 mutations as well as loss of paranodal junctions and disorganization of axonal domains in myelinated axons. Expression of the wild type Cntnap1 transgene in Cntnap1 mice rescued the mutant phenotypes and restored all neurological deficits. Our studies demonstrate that GGT (glycine) to GTT (valine) change in human CNTNAP1 creates a recessive loss of function allele and lays the foundation for potential gene therapy studies aimed at treating CNTNAP1-associated hypomyelinating neuropathies in children.
RETRACTION: Neuroactive Molecules and Growth Factors Modulate Cytoskeletal Protein Expression During Astroglial Cell Proliferation and Differentiation in Culture.
J Neurosci Res · 2025 Apr · PMID 40260586 · Publisher ↗
V. Bramanti, S. Grasso, D. Tibullo, C. Giallongo, R. Pappa, MV Brundo, D. Tomassoni, M. Viola, F. Amenta, and R. Avola, "Neuroactive Molecules and Growth Factors Modulate Cytoskeletal Protein Expression During Astroglial...
V. Bramanti, S. Grasso, D. Tibullo, C. Giallongo, R. Pappa, MV Brundo, D. Tomassoni, M. Viola, F. Amenta, and R. Avola, "Neuroactive Molecules and Growth Factors Modulate Cytoskeletal Protein Expression During Astroglial Cell Proliferation and Differentiation in Culture," Journal of Neuroscience Research 94, no. 1 (2016): 90-98, https://doi.org/10.1002/jnr.23678. The above article, published online on 15 October 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Lawrence S. Sherman; and John Wiley & Sons, Inc. Following publication, concerns were raised by a third party that portions of Figures 2B and 3 were duplicated and manipulated, and that most of the images from Figure 2A were duplicated and manipulated from an earlier publication by this research group. Internal investigation confirmed these claims. The publisher attempted to contact the authors and request original data, but the authors did not respond. The retraction has been agreed because of concerns that the images were manipulated, affecting the interpretation of the data and results presented. The authors have been notified of the retraction.
RETRACTION: Effect of growth factors and steroids on transglutaminase activity and expression in primary astroglial cell cultures.
J Neurosci Res · 2025 Apr · PMID 40260576 · Publisher ↗
A. Campisi, V. Bramanti, D. Caccamo, G. Li Volti, G. Cannavò, M. Currò, G. Raciti, F. Galvano, F. Amenta, A. Vanella, R. Ientile, R. Avola, "Effect of growth factors and steroids on transglutaminase activity and expressi...
A. Campisi, V. Bramanti, D. Caccamo, G. Li Volti, G. Cannavò, M. Currò, G. Raciti, F. Galvano, F. Amenta, A. Vanella, R. Ientile, R. Avola, "Effect of growth factors and steroids on transglutaminase activity and expression in primary astroglial cell cultures," Journal of Neuroscience Research 86, no. 6 (2008): 1297-1305, https://doi.org/10.1002/jnr.21579. The above article, published online on 26 November 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Lawrence S. Sherman; and John Wiley & Sons, Inc. Following publication, concerns were raised by a third party that portions of Figures 1 and 8 were duplicated and manipulated, and that portions of Figure 8 were duplicated from an earlier publication by this research group. Internal investigation confirmed these claims. The publisher attempted to contact the authors and request original data, but the authors did not respond. The retraction has been agreed because of concerns that the images were manipulated, affecting the interpretation of the data and results presented. The authors have been notified of the retraction.
EXPRESSION OF CONCERN: Lithium Inhibits Aβ-Induced Stress in Endoplasmic Reticulum of Rabbit Hippocampus but Does Not Prevent Oxidative Damage and Tau Phosphorylation.
J Neurosci Res · 2025 Apr · PMID 40259881 · Publisher ↗
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EXPRESSION OF CONCERN: Gene Expression Profile Activated by the Chemokine CCL5/RANTES in Human Neuronal Cells.
J Neurosci Res · 2025 Apr · PMID 40259847 · Publisher ↗
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Sex and Strain Differences in Analgesic and Hyperlocomotor Effects of Morphine and μ-Opioid Receptor Expression in Mice.
Boorman DC, Rehal SK, Fazili M … +1 more , Martin LJ
J Neurosci Res · 2025 Apr · PMID 40247818 · Full text
Sex and gender differences in the analgesic efficacy and side effects of opioids have been widely reported, but their underlying neurobiological mechanisms remain poorly understood. Preclinical animal models are essentia...
Sex and gender differences in the analgesic efficacy and side effects of opioids have been widely reported, but their underlying neurobiological mechanisms remain poorly understood. Preclinical animal models are essential tools for investigating these differences and providing insights into the neurobiology of opioid effects. Although studies in rats have revealed sex-specific effects of opioids, the sex-dependent behavioral profiles of opioids in mice, particularly across strains, remain largely unexplored. In this study, we characterized sex and strain differences in the antinociceptive and hyperlocomotor effects of morphine in the two most widely used mouse strains-CD1 and C57BL/6-and quantified regional expression of the μ-opioid receptor (MOR) in key brain and spinal cord regions. Both strains exhibited clear, dose-dependent antinociceptive and hyperlocomotor responses to morphine. While no significant sex or strain differences were observed in antinociceptive effects, C57BL/6 mice displayed significantly greater hyperlocomotor activity than CD1 mice. Western blot analyses revealed strain-specific MOR expression, with CD1 mice showing higher spinal cord and periaqueductal gray MOR levels, particularly in females, while C57BL/6 mice exhibited elevated MOR expression in the caudoputamen. Morphine treatment increased spinal MOR expression in CD1 mice but not C57BL/6, suggesting strain-dependent regulation of MOR. These findings highlight strain-specific behavioral and molecular responses to morphine, emphasizing the importance of strain and sex considerations in preclinical opioid research.
Quantitative MRI of the Spinal Cord and Brain in Chronic Traumatic Spinal Cord Injury: In Vivo Assessment of Structural Changes.
Li J, Zhao X, Shan Y … +9 more , Shan G, Wei PH, Liu L, Wang C, Wu H, Song W, Tang Y, Zhao GG, Lu J
J Neurosci Res · 2025 Apr · PMID 40212012 · Publisher ↗
The prolonged survival of traumatic spinal cord injury (TSCI) patients underscores the need to customize rehabilitative treatment plans according to patients' characteristics, aiming to restore motor function. We conduct...
The prolonged survival of traumatic spinal cord injury (TSCI) patients underscores the need to customize rehabilitative treatment plans according to patients' characteristics, aiming to restore motor function. We conducted a cross-sectional study of two groups with chronic TSCI (short-term group: 11 patients with an injury time of 1-2 years; long-term group: 10 patients with an injury time > 2 years) and 16 controls. Quantitative MRI was used to evaluate structural changes in the upper spinal cord and brain. Compared to controls, both groups exhibited decreased fractional anisotropy (close relationship of the decreased) in the spinal cord, and the long-term group showed reduced spinal cord cross-sectional areas. The short-term group presented increased gray matter volumes (GMVs) in the paracentral lobule, postcentral gyrus, and supplementary motor area, indicating compensatory neural changes, whereas the long-term group exhibited decreased GMV in cerebellar lobule VI, suggesting weakening of the signal received by the cerebellum. Track-based spatial statistics revealed the close relationship of the decreased FA was with the increased radial diffusivity in the long-term group, indicating that demyelination mainly altered the white matter. Correlation analysis revealed that the increased GMV was negatively correlated with the sensorimotor score (r = -0.725, p = 0.018). Additionally, the GMV of cerebellar lobule VI was positively correlated with the sensorimotor score (r = 0.671, p = 0.024). In summary, quantitative MRI identifies structural changes in the brain and spinal cord of patients with chronic TSCI that vary with the time since injury and provide imaging evidence for the development of precise targeted therapies.
Early Life Stress Induces Brain Mitochondrial Dynamics Changes and Sex-Specific Adverse Effects in Adulthood.
Vlaikou AM, Nussbaumer M, Iliou A … +8 more , Papageorgiou MP, Komini C, Theodoridou D, Benaki D, Mikros E, Gikas E, Syrrou M, Filiou MD
J Neurosci Res · 2025 Apr · PMID 40195806 · Publisher ↗
Early life stress exposure exerts detrimental effects in adulthood and is a risk factor for psychiatric disorders. Studies addressing the molecular mechanisms of early life stress have primarily focused on hormones and s...
Early life stress exposure exerts detrimental effects in adulthood and is a risk factor for psychiatric disorders. Studies addressing the molecular mechanisms of early life stress have primarily focused on hormones and stress circuits. However, little is known on how mitochondria and mitochondrial dynamics (i.e., the orchestration of mitochondrial fission, fusion, mitophagy, and biogenesis) modulate early life stress responses. Here, we used a maternal separation with early weaning (MSEW) paradigm to investigate the behavioral and molecular early life stress-elicited effects in male and female C57BL/6 mice in adulthood. We first applied a behavioral test battery to assess MSEW-driven, anxiety-related and stress-coping alterations. We then looked for MSEW-induced, mitochondria-centered changes in cingulate cortex, hippocampus and cerebellum, as well as in plasma by combining protein, mRNA, mitochondrial DNA copy number (mtDNAcn) and metabolomics analyses. We found that MSEW mice are more anxious, show decreased antioxidant capacity in the cingulate cortex and have higher mRNA levels of the fission regulator Fis1 and the mitophagy activator Pink1 in the hippocampus, indicating a shift towards mitochondrial degradation. Hippocampal mRNA level alterations of apoptotic markers further suggest an MSEW-driven activation of apoptosis accompanied by a dysregulation of purine catabolism in the cerebellum in MSEW mice. Sex-specific analysis revealed distinct MSEW-induced changes in male and female mice at the molecular level. Our work reveals a previously unexplored role of mitochondrial dynamics in regulating early life stress effects and highlights a mitochondria-centered dysregulation as a persistent outcome of early life stress in adulthood.
Cannabidiol-Rich Cannabis sativa L. Extract Alleviates LPS-Induced Neuroinflammation Behavioral Alterations, and Astrocytic Bioenergetic Impairment in Male Mice.
Ibork H, Ait Lhaj Z, Boualam K … +7 more , El Idrissi S, B Ortaakarsu A, Hajji L, Manalo Morgan A, Khallouki F, Taghzouti K, Abboussi O
J Neurosci Res · 2025 Apr · PMID 40195769 · Publisher ↗
Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited. This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) e...
Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited. This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model. The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors. Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties. The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding. These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.
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