Search Results (1,300)

The failure of endogenous repair mechanisms is a key characteristic of neurological diseases, leading to the inability to restore damaged nerves and resulting in functional impairments. Since the endogenously regenerative capacity of damaged nerves is limited, the enhancement of regenerative potential of quiescent neural stem cells (NSCs) presents as a therapeutic option for neural diseases. Our previous studies have shown exciting progress in treating sciatic nerve injury in mice and rats using NSCs in conjunction with neurotrophic factors such as fibroblast growth factor 1 (FGF1). Additionally, a recently discovered neurotrophic factor, IL12p80, has shown significant therapeutic effects in sciatic nerve injury repair via myelinating oligodendrocytes. IL12p80 induces oligodendrocyte differentiation from NSCs through phosphorylation of Stat3. Therefore, it might be possible to alleviate the myelination defects of oligodendrocytes in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and even schizophrenia through the administration of IL12p80. These applications could shed light on IL12p80 and FGF1, not only in damaged nerve repair, but also in rectifying the oligodendrocytes’ defects in neurodegenerative diseases, such as ALS and MS. Finally, the synergistic effects of neurogenesis-induced FGF1 and myelination-induced IL12 might be able to supplant the need of NSCs for nerve repair and neuroregeneration. Full article

The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood–brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain’s immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies. Full article

The dehydrated human amnion–chorion membranes (dHACMs) derived from the human placenta have emerged as a promising biomaterial for dental pulp regeneration owing to their unique biological and structural properties. The purpose of this review is to explore the potentials of dHACMs in dental pulp tissue engineering, focusing on their ability to promote cellular proliferation, differentiation, angiogenesis, and neurogenesis. dHACMs are rich in extracellular matrix proteins and growth factors such as TGF-β1, FGF2, and VEGF. They also exhibit significant anti-inflammatory and antimicrobial properties, creating an optimal environment for dental pulp regeneration. The applications of dHACMs in regenerative endodontic procedures are discussed, highlighting their ability to support the formation of dentin and well-vascularized pulp-like tissue. This review demonstrates that dHACMs hold significant potential for enhancing the success of pulp regeneration and offer a biologically based approach to preserve tooth vitality and improve tooth survival. Future research is expected to focus on conducting long-term clinical studies to establish their efficacy and safety. Full article

Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy. This study examines the role of microglia and axonal guidance molecules in neuronal reorganization in TLE. Methods: Nineteen hippocampal samples from patients with TLE undergoing epilepsy surgery were analyzed. Microglial activity (M1/M2-like microglia) and neuronal guidance molecules were assessed using microscopy and semi-automated techniques. Gene expression was evaluated using the nCounter Expression Profiling method. Results: Neuronal cell loss was correlated with decreased activity of the M1 microglial phenotype. In the CA2 region, neuronal preservation was linked to increased mossy fiber sprouting and microglial presence. Neuronal markers such as Deleted in Colorectal Cancer (DCC) and Synaptopodin were reduced in areas of cell death, while Netrin-1 was elevated in the granule cell layer, potentially influencing mossy fiber sprouting. The nCounter analysis revealed downregulation of genes involved in neuronal activity (e.g., NPAS4, BCL-2, GRIA1) and upregulation of IκB, indicating reduced neuroinflammation. Conclusions: This study suggests reduced neuroinflammation in areas of neuronal loss, while regions with preserved neurons showed mossy fiber sprouting associated with microglia, Netrin-1, and DCC. Full article

Ocimum sanctum Linn (O. sanctum L.), commonly known as Holy Basil or Tulsi, is a fragrant herbaceous plant belonging to the Lamiaceae family. This plant is widely cultivated and found in north-central parts of India, several Arab countries, West Africa and tropical regions of the Eastern World. Tulsi is known to be an adaptogen, aiding the body in adapting to stress by harmonizing various bodily systems. Revered in Ayurveda as the “Elixir of Life”, Tulsi is believed to enhance lifespan and foster longevity. Eugenol, the active ingredient present in Tulsi, is a l-hydroxy-2-methoxy-4-allylbenzene compound with diverse therapeutic applications. As concerns over the adverse effects of conventional antibacterial agents continue to grow, alternative therapies have gained prominence. Essential oils (EOs) containing antioxidants have a long history of utilization in traditional medicine and have gained increasing popularity over time. Numerous in vitro, in vivo and clinical studies have provided compelling evidence supporting the safety and efficacy of antioxidant EOs derived from medicinal plants for promoting health. This comprehensive review aims to highlight the scientific knowledge regarding the therapeutic properties of O. sanctum, focusing on its antibacterial, anti-diabetic, anti-carcinogenic, radioprotective, immunomodulatory, anti-inflammatory, cardioprotective, neurogenesis, anti-depressant and other beneficial characteristics. Also, the extracts of O. sanctum L. have the ability to reduce chronic inflammation linked to neurological disorders such as Parkinson’s and Alzheimer’s disease. The information presented in this review shed light on the multifaceted potential of Tulsi and its derivatives in maintaining and promoting health. This knowledge may pave the way for the development of novel therapeutic interventions and natural remedies that harness the immense therapeutic potential of Tulsi in combating various health conditions, while also providing valuable insights for further research and exploration in this field. Full article

Background/Objectives: Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to the differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation in Drosophila larval brains. Methods: We quantified tRNA abundance in neural progenitor-biased and neuron-biased brains using the hydrotRNA-seq method. These tRNA data were combined with cell type-specific mRNA decay measurements and transcriptome profiles in order to model how tRNA abundance affects mRNA stability and translation efficiency. Results: We found that (1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, (2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons, but does not completely explain the different stabilizing or destabilizing effects of certain codons, and (3) changes in tRNA levels support a shift in translation optimization from a program supporting proliferation to a program supporting differentiation. Conclusions: These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development. Full article

Accurate normalization in miRNA studies requires the use of appropriate endogenous controls, which can vary significantly depending on cell types, treatments, and physiological or pathological conditions. This study aimed to identify suitable endogenous miRNA controls for neural progenitor cells (NPCs) and hippocampal tissues, both of which play crucial roles in neurogenesis. Using small RNA sequencing, we identified the most stable miRNAs in primary mouse NPCs and hippocampal tissues and accessed their stability using NormFinder analysis. Six miRNAs—miR-181d-5p, miR-93-5p, miR-103-3p, let-7d-5p, miR-26a-5p, and miR-125a-5p—demonstrated high stability and were evaluated for their suitability as endogenous controls across multiple experimental conditions. All selected miRNAs exhibited consistent expression in the NE-4C mouse cell line but not in ReNcells, a human cell line. For ReNcells, only miR-186-5p, one of the known reference miRNAs tested for comparison, showed stable expression. Notably, miR-103-3p and let-7d-5p were stably expressed in hippocampal tissues from both mouse and human samples but were absent in human brain pericytes, human brain microvascular endothelial cells, and SVG p12 cells, a human fetal glial cell line. This study is the first to identify optimal reference miRNAs for adult neurogenesis in both mouse and human samples, providing reliable options for miRNA normalization and improving the accuracy and reproducibility of miRNA expression analyses in neurogenesis research. Full article

Background: Ischemic stroke results from a disruption of cerebral blood flow. Adrenocorticotropic hormone (ACTH) serves as the basis for the creation of synthetic peptides as neuroprotective agents for stroke therapy. Previously, using RNA-Seq we first revealed differential expressed genes (DEGs) associated with ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP peptides under cerebral ischemia conditions. Analysis was carried out at 4.5 h after transient middle cerebral artery occlusion (tMCAO) model in the ipsilateral frontal cortex of a rat brain. Methods: Here, we analyzed the penumbra-associated frontal cortex of rats and actions under the same peptides at 24 h after tMCAO using RNA-Seq. Results: 3774 DEGs (fold change > 1.5 and Padj < 0.05) were identified under ischemia conditions, whereas 1539 and 2066 DEGs were revealed under Semax and ACTH(6–9)PGP peptides at 24 h after tMCAO. Furthermore, both peptides significantly reduced expression distortions caused by ischemia for 1171 genes associated with immune and neurosignaling pathways. Concomitantly, there were 32 DEGs under ACTH(6–9)PGP versus Semax administration at 24 h after tMCAO. Besides, neurogenesis-, angiogenesis-, protein kinase- and growth factor-related DEGs were revealed under peptides action. Previously, we observed the neuroprotective effect of peptides at the histological level in rat brains at 24 h after tMCAO. Thus, here we demonstrate the transcriptome manifestation of this histological effect. Furthermore, comparison with previous data at the 4.5 h post-tMCAO time point showed that the pattern of peptide action on the transcriptome depends on the time elapsed after tMCAO. Conclusions: We revealed that the effect of ACTH(6–9)PGP was more similar to Semax than different from it a day after tMCAO. At this time point, ACTH-like peptides compensated rat brain gene expression profiles disrupted by ischemia. Thus, our results may be useful for selecting more effective structures for future anti-stroke drugs and appropriate post-stroke time points for their testing. Full article

Nervous system diseases represent a significant global burden, affecting approximately 16% of the world’s population and leading to disability and mortality. These conditions, encompassing both central nervous system (CNS) and peripheral nervous system (PNS) disorders, have substantial social and economic impacts. Metformin, a guanidine derivative derived from a plant source, exhibits therapeutic properties in various health conditions such as cancer, aging, immune-related disorders, polycystic ovary syndrome, cardiovascular ailments, and more. Recent studies highlight metformin’s ability to cross the blood–brain barrier, stimulate neurogenesis, and provide beneficial effects in specific neurological disorders through diverse mechanisms. This review discusses the advancements in research on metformin’s role and mechanisms in treating neurological disorders within both the central and peripheral nervous systems, aiming to facilitate further investigation, utilization, and clinical application of metformin in neurology. Full article

Down syndrome (DS) is characterized by severe neurodevelopmental alterations that ultimately lead to the typical hallmark of DS: intellectual disability. In the DS brain, since the prenatal life stages, the number of astrocytes is disproportional compared to the healthy brain. This increase is due to a shift from neuron to astrocyte differentiation during brain development. Astrocytes are involved in numerous functions during brain development, including balancing pro-neurogenic and pro-gliogenic stimuli, sustaining synapse formation, regulating excitatory/inhibitory signal equilibrium, and supporting the maintenance and integration of functional neural circuits. The enhanced number of astrocytes in the brain of DS individuals leads to detrimental consequences for brain development. This review summarizes the mechanisms underlying astrocytic dysfunction in DS, and particularly the dysregulation of key signaling pathways, which promote astrogliogenesis at the expense of neurogenesis. It further examines the implications of astrocytic alterations on dendritic branching, spinogenesis and synaptogenesis, and the impact of the abnormal astrocytic number in neural excitability and in the maintenance of the inhibitory/excitatory balance. Identifying deregulated pathways and the consequences of astrocytic alterations in early DS brain development may help in identifying new therapeutic targets, with the ultimate aim of ameliorating the cognitive disability that affects individuals with DS. Full article

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation. In the current study, we examined the postnatal DG neuron morphology one month after delivery (P28) using recombinant adeno-associated viral labeling of neurons. We also examined DG microglia’s morphology using immunofluorescent histochemistry and defined the hippocampal cytokine/chemokine milieu using Luminex xMAP technology. We found that IUGR preserved the principal dendrite lengths but decreased the dendritic branching and volume of DG neurons. IUGR augmented DG microglial number and cell size. Lastly, IUGR altered the hippocampal cytokine/chemokine profile in a sex-specific manner. We conclude that the prematurely-generated neuronal progenitors develop abnormal morphologies postnatally in a cell-autonomous manner. Microglia appear to modulate neuronal morphology by interacting with dendrites amidst a complex cytokine/chemokine environment that could ultimately lead to adult learning and memory deficits in our mouse model. Full article

The glycosylphosphatidylinositol (GPI) is a glycol–lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children. Among them, the PIGO gene encodes for phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO), an enzyme participating in this cascade, and the loss of its function often leads to a severe clinical picture characterized by global developmental delay, seizures, Hirschsprung disease, and other congenital malformations. To date, 19 patients with confirmed PIGO deficiency have been described in the literature with a host of clinical and radiological manifestations. We report a case of a male term newborn with two compound heterozygous variants of the PIGO genes, presenting with encephalopathy, drug-resistant epilepsy, and gastrointestinal abnormalities. Brain MRI first showed diffusion restriction in the ponto-medullary tegmentum, ventral mesencephalon, superior cerebellar peduncles, cerebral peduncles, and globi pallidi. This pattern of lesion distribution has been described as part of the neuroradiological spectrum of PIG genes-related disorders. However, after one month of life, he also showed a previously undescribed MRI pattern characterized by extensive cortical and subcortical involvement of the brain hemispheres. The presence of two different mutations in both the PIGO genes may have been responsible for the particularly severe clinical picture and worse outcome, leading to the death of the newborn in the sixth month of life despite therapeutic attempts. This case expands the neuroradiological spectrum and may bring new insights on glycosylation-related disorders brain manifestations. Full article

Multiple sclerosis (MS) is a chronic neurodegenerative disorder involving demyelination. The cuprizone model is commonly used to study MS by inducing oligodendrocyte stress and demyelination. The subventricular zone (SVZ) plays a key role in neurogenesis, while the neuronal/glial antigen 2 (NG2) is a marker for immature glial cells, involved in oligodendrocyte differentiation. The apelin receptor (APLNR) is linked to neurogenesis and behavior modulation. This study explores the role of APLNR in NG2-positive cells during de- and remyelination phases in the experimental cuprizone mouse model. Thirty male C57BL/6 mice were divided into control (not treated), demyelination (5 weeks cuprizone administration), and remyelination (5 weeks cuprizone administration + 5 weeks recovery) groups. Histological examinations, immunohistochemistry, and immunofluorescence on serial coronal sections were conducted to evaluate corpus callosum (CC) morphology and APLNR and NG2 expression in the SVZ, in addition to behavioral assessments. The histological analysis showed a significant reduction in the CC’s thickness and area after five weeks of cuprizone exposure, followed by recovery five weeks post-exposure. During the demyelination phase, APLNR-expressing cells peaked while NG2-positive cells decreased. In the remyelination phase, APLNR-expressing cells declined, and NG2-positive cells increased. Confocal microscopy confirmed the co-localization of NG2 and APLNR markers. Statistically significant differences were observed across experimental groups. Correlation analyses highlighted associations between APLNR/NG2 cell counts and CC changes. Behavioral tests revealed impaired motor coordination and memory during demyelination, with gradual recovery during remyelination. Significant changes in the CC structure and the number of APLNR and NG2-positive cells were observed during de- and remyelination, suggesting that NG2-positive cells expressing APLNR may play a key role in remyelination. Full article

This paper bridges critical gaps through proposing a novel, environmentally mediated brain-derived neurotrophic factor (BDNF)-interactive model that promises to sustain adult hippocampal neurogenesis in humans. It explains how three environmental enrichment mechanisms (physical activity, cognitive stimulation, and mindfulness) can integratively regulate BDNF and other growth factors and neurotransmitters to support neurogenesis at various stages, and how those mechanisms can be promoted by the physical environment. The approach enables the isolation of specific environmental factors and their molecular effects to promote sustainable BDNF regulation by testing the environment’s ability to increase BDNF immediately or shortly before it is consumed for muscle repair or brain update. This model offers a novel, feasible method to research environment enrichment and neurogenesis dynamics in real-world human contexts at the immediate molecular level, overcoming the confounds of complex environment settings and challenges of long-term exposure and structural plasticity changes. The model promises to advance understanding of environmental influences on the hippocampus to enhance brain health and cognition. This work bridges fundamental gaps in methodology and knowledge to facilitate more research on the enrichment–neuroplasticity interplay for humans without methodological limitations. Full article

The coexistence of dementia and depression in older populations presents a complex clinical challenge, with each condition often exacerbating the other. Cognitive decline can intensify mood disturbances, and untreated or recurring depression accelerates neurodegenerative processes. As depression is a recognized risk factor for dementia, it is crucial to address both conditions concurrently to prevent further deterioration. Antidepressants are frequently used to manage depression in dementia patients, with some studies suggesting they offer neuroprotective benefits. These benefits include promoting neurogenesis, enhancing synaptic plasticity, and reducing neuroinflammation, potentially slowing cognitive decline. Additionally, antidepressants have shown promise in addressing Alzheimer’s-related pathologies by reducing amyloid-beta accumulation and tau hyperphosphorylation. However, treatment-resistant depression remains a significant challenge, particularly in older adults with cognitive impairment. Many do not respond well to standard antidepressant therapies due to advanced neurodegenerative changes. Conflicting findings from studies add to the uncertainty, with some research suggesting that antidepressants may increase dementia risk, especially when used in patients with undiagnosed early-stage dementia. This article aims to explore the intricate relationship between depression and dementia, examining the benefits and risks of antidepressant use. We highlight the urgent need for personalized, comprehensive treatment strategies that balance mental health improvement with cognitive protection. Full article