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Chinese Journal of Integrative Medicine Nov 2023To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic...
OBJECTIVE
To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice.
METHODS
Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively.
RESULTS
Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01).
CONCLUSIONS
OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota.
PubMed: 37999886
DOI: 10.1007/s11655-023-3614-3 -
Pediatric and Developmental Pathology :... 2024Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically...
Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including and . Pathogenic gene variants cause Coffin-Siris syndrome 3 whereas pathogenic gene variants cause Coffin-Siris syndrome 2. Here, we present two prenatal Coffin-Siris syndrome cases with autosomal dominant pathogenic variants: gene c.1066_1067del, p.(Leu356AspfsTer4) variant, and a novel gene c.1920+3_1920+6del variant. The prenatal phenotype in Coffin-Siris syndrome has been rarely described. This article widens the phenotypic spectrum of prenatal Coffin-Siris syndrome with severely hypoplastic right ventricle with VSD and truncus arteriosus type III, persisting left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus. A detailed clinical description of the patients with ultrasound, MRI, and pictures of the affected fetuses showing the wide phenotypic spectrum of the disease is presented.
Topics: Humans; Intellectual Disability; Abnormalities, Multiple; Face; Phenotype; Hand Deformities, Congenital; Micrognathism; Neck
PubMed: 37981638
DOI: 10.1177/10935266231210155 -
Expert Review of Clinical Pharmacology 2023This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings. (Randomized Controlled Trial)
Randomized Controlled Trial
The effectiveness of cerebrolysin, a multi-modal neurotrophic factor, for treatment of post-covid-19 persistent olfactory, gustatory and trigeminal chemosensory dysfunctions: a randomized clinical trial.
BACKGROUND
This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings.
RESEARCH DESIGN AND METHODS
This was a prospective randomized trial. It included 250 patients (male = 93, female = 157; age: 31.3 ± 8.9 years). Patients were randomized into group 1 ( = 150): received cerebrolysin [5 ml/d (IM), 5d/week] and practiced olfactory and gustatory trainings, and group 2 ( = 100): practiced olfactory and gustatory trainings only, for ≥ 8-24 weeks. Measures of outcomes were: a clinical questionnaire; sniffin' odor, taste and flavor identification tests; and global rating scales for smell and taste.
RESULTS
The duration of disorders was 11.7 ± 3.7mo (range: 6-24mo). The majority ( = 167; 66.8%) developed parosmia within months (3.6 ± 2.7mo) after anosmia. Objective testing showed anosmia in all and taste, flavor, and trigeminal sensory losses in 18% ( = 45). Analyses for secondary outcome were done on 202 patients (group 1 = 130; group 2 = 72). Recovery was complete in 61.5% ( = 80) with cerebrolysin therapy and partial in 17% ( = 22). There was no recovery with trainings only. There were no predictors for recovery.
CONCLUSIONS
Cerebrolysin had fast, promising, and constant effect, with cure rate of > 60%. This might be due to its ability to initiate and enhance neuronal regeneration and reorganization of sensory epithelia.
TRIAL REGISTRATION
NCT04830943.
Topics: Humans; Male; Female; Young Adult; Adult; Smell; COVID-19; Anosmia; Prospective Studies; Nerve Growth Factors
PubMed: 37950370
DOI: 10.1080/17512433.2023.2282715 -
Neuropeptides Feb 2024Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system...
Effect of valproic acid combined with transplantation of olfactory ensheathing cells modified by neurotrophic 3 gene on nerve protection and repair after traumatic brain injury.
BACKGROUND
Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system diseases; the neurotrophin 3 gene (NT-3) can maintain the survival of neurons, and olfactory ensheathing cells (OECs) can promote the growth of nerve axons. This study aimed to evaluate the restorative effect of VPA combined with NT-3 modified OECs (NT-3-OECs) on neurological function after TBI.
METHODS
The neurological severity score (NSS) of rats was evaluated on the 1st, 7th, 14th, and 28th day after TBI modeling and corresponding intervention. Hematoxylin-eosin (HE) staining, p75 nerve growth factor receptor (P75), glial fibrillary acidic protein (GFAP), and neurofilament protein (NF)staining, and argyrophilic staining were used to observe the morphology of brain tissue 28 days after modeling. Moreover, TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptosis rate of neurons. The changes in synapses and mitochondria in the injured area were observed by electron microscope.
RESULTS
NT-3-OECs transplantation can increase the content of NT-3 in brain tissue, and NT-3-OECs can survive for >28 days. The NSS score of the TBI-VPA-NT-3-OECs group 28 days after cell transplantation was significantly lower than that of the other model treatment groups (P < 0.05). The morphological structure of the brain tissue was more complete, and the neurofilament fibers were neatly arranged, achieving better results than those of the other groups. The apoptosis rate of nerve cells in the TBI-VPA-NT-3-OECs group was significantly lower than in the other treatment groups (P < 0.05). Furthermore, the number of synapses in the combined intervention group was significantly higher than in the other treatment groups, and the mitochondrial structure was more complete.
CONCLUSION
NT-3-OECs have good biological function, and VPA combined with NT-3-OECs transplantation can effectively improve the prognosis of TBI rats.
Topics: Rats; Animals; Rats, Sprague-Dawley; Valproic Acid; Brain Injuries, Traumatic; Neurons; Cell Transplantation; Olfactory Bulb
PubMed: 37945445
DOI: 10.1016/j.npep.2023.102389 -
International Journal of Infectious... Jan 2024Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but...
OBJECTIVES
Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children.
METHODS
A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients.
RESULTS
A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis.
CONCLUSION
Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.
Topics: Adult; Humans; Child; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Posterior Leukoencephalopathy Syndrome; Neuroimaging; Systemic Inflammatory Response Syndrome
PubMed: 37944584
DOI: 10.1016/j.ijid.2023.11.006 -
Frontiers in Neuroscience 2023Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on...
Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on neuronal activity in several brain regions have been identified, a comprehensive evaluation of the whole brain is still lacking. Hence, we performed SD using two different methods, gentle handling and a dedicated chamber, in targeted recombination in active populations 2 (TRAP2) mice crossed with Rosa-ZsGreen reporter mice and visualized cellular activity in the whole brain. Using the semi-automated post-imaging analysis tool Slice Histology Alignment, Registration, and Cell Quantification (SHARCQ), the number of activated cells was quantified. From the analysis of 14 brain regions, cellular activity was significantly increased in the olfactory areas and decreased in the medulla by the two SD methods. From the analysis of the further subdivided 348 regions, cellular activity was significantly increased in the vascular organ of the lamina terminalis, lateral hypothalamic area, parabigeminal nucleus, ventral tegmental area, and magnocellular reticular nucleus, and decreased in the anterior part of the basolateral amygdalar nucleus, nucleus accumbens, septohippocampal nucleus, reticular nucleus of the thalamus, preoptic part of the periventricular hypothalamic nucleus, ventromedial preoptic nucleus, rostral linear nucleus raphe, facial motor nucleus, vestibular nuclei, and some fiber tracts (oculomotor nerve, genu of corpus callosum, and rubrospinal tract) by the two SD methods. Two subdivided regions of the striatum (caudoputamen and other striatum), epithalamus, vascular organ of the lamina terminalis, anteroventral preoptic nucleus, superior colliculus optic layer, medial terminal nucleus of the accessory optic tract, pontine gray, and fiber tracts (medial lemniscus, columns of the fornix, brachium of the inferior colliculus, and mammillary peduncle) were differentially affected by the two SD methods. Most brain regions detected from these analyses have been reported to be involved in regulating sleep/wake regulatory circuits. Moreover, the results from the connectivity analysis indicated that the connectivity of cellular activity among brain regions was altered by SD. Together, such a comprehensive analysis of the whole brain is useful for understanding the mechanisms by which SD and/or sleep disruption affects brain function.
PubMed: 37928729
DOI: 10.3389/fnins.2023.1252689 -
Frontiers in Immunology 2023Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss... (Review)
Review
Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.
Topics: Humans; Neurodegenerative Diseases; Peripheral Nerve Injuries; Axons; Nerve Regeneration; Olfactory Bulb
PubMed: 37915589
DOI: 10.3389/fimmu.2023.1280186 -
Neural Regeneration Research Jun 2024Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized...
Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosome-based treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
PubMed: 37905871
DOI: 10.4103/1673-5374.385875 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Aug 2023Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural... (Review)
Review
Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural circuitry underlying congenital fear can offer insights into the pathophysiological mechanisms of related psychiatric conditions. Research on innate fear primarily centers on the response mechanisms to various sensory signals, including olfactory, visual and auditory stimuli. Different types of fear signal inputs are regulated by distinct neural circuits. The neural circuits of the main and accessory olfactory systems receive and process olfactory stimuli, mediating defensive responses like freezing. Escape behaviors elicited by visual stimuli are primarily regulated through the superior colliculus and hypothalamic projection circuits. Auditory stimuli-induced responses, including escape, are mainly mediated through auditory cortex projection circuits. In this article, we review the research progress on neural circuits of innate fear defensive behaviors in animals. We further discuss the different sensory systems, especially the projection circuits of olfactory, visual and auditory systems, to provide references for the mechanistic study of related mental disorders.
Topics: Animals; Humans; Fear; Nerve Net
PubMed: 37899403
DOI: 10.3724/zdxbyxb-2023-0131 -
Arthropod Structure & Development Nov 2023Immunohistochemical analyses on the distribution of neuropeptides in the pancrustacean brain in the past have focussed mostly on representatives of the decapod...
Immunolocalization of SIFamide-like neuropeptides in the adult and developing central nervous system of the amphipod Parhyale hawaiensis (Malacostraca, Peracarida, Amphipoda).
Immunohistochemical analyses on the distribution of neuropeptides in the pancrustacean brain in the past have focussed mostly on representatives of the decapod ("ten-legged") pancrustaceans whereas other taxa are understudied in this respect. The current report examines the post-embryogenic and adult brain and ventral nerve cord of the amphipod pancrustacean Parhyale hawaiensis (Dana. 1853; Peracarida, Amphipoda, Hyalide), a subtropical species with a body size of 1.5 cm and a direct post-embryonic development using immunohistochemistry to label the neuropeptide SIFamide and synaptic proteins (synapsins). We found strong SIFamide-like labelling in proto-, deuto- and tritocerebrum, especially in the lamina, the lateral protocerebrum, lateral assessory lobe, the central body, olfactory lobe, medial antenna 1 neuropil and antenna 2 neuropil. Out of a total of 28 ± 5 (N = 12) SIFamide-positive neurons in the central brain of adult P. hawaiensis, we found three individually identifiable somata which were consistently present within the brain of adult and subadult animals. Additionally, the subesophageal and two adjacent thoracic ganglia were analysed in only adult animals and also showed a strong SIFamide-like immunoreactivity. We compare our findings to other pancrustaceans including hexapods and discuss them in an evolutionary context.
Topics: Animals; Amphipoda; Neuropeptides; Neurons; Brain; Neuropil
PubMed: 37879171
DOI: 10.1016/j.asd.2023.101309