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Neurology(R) Neuroimmunology &... Jul 2024To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in...
OBJECTIVES
To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS).
METHODS
People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated.
RESULTS
A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; = 0.04), cortical gray matter (rho = 0.34; = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; = 0.04) and cortical gray matter (rho = 0.31; = 0.049) atrophy.
DISCUSSION
NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.
Topics: Humans; Male; Female; Middle Aged; Extracellular Vesicles; Adult; Atrophy; Brain; Retina; Multiple Sclerosis; Synaptophysin; Tomography, Optical Coherence; Magnetic Resonance Imaging; Microfilament Proteins
PubMed: 38754047
DOI: 10.1212/NXI.0000000000200257 -
EXCLI Journal 2024Alzheimer's disease remains an issue of great controversy due to its pathology. It is characterized by cognitive impairments and neuropsychiatric symptoms. The FDA...
Alzheimer's disease remains an issue of great controversy due to its pathology. It is characterized by cognitive impairments and neuropsychiatric symptoms. The FDA approved medications for this disease, can only mitigate the symptoms. One reason for the lack of effective medications is the inaccessibility of the brain which is encompassed by the blood-brain barrier, making intranasal (IN) route of administration potentially advantageous. Male Wistar rats underwent stereotaxic surgery to induce an Alzheimer's disease model via intracerebroventricular (ICV) streptozotocin injection, and Carbamylated Erythropoietin-Fc (CEPO-FC), a derivative of Erythropoietin without its harmful characteristics, was administered intranasally for ten consecutive days. Cognition performance for memory and attention was assessed using the Novel Object Recognition Test and the Object-Based Attention Test respectively. Depression like behavior was evaluated using the Forced Swim Test. Western blotting was done on the extracted hippocampus to quantify STIM proteins. Calbindin, PSD-95, Neuroplastin, Synaptophysin and GAP-43 genes were assessed by Realtime PCR. Behavioral tests demonstrated that IN CEPO-FC could halt cognition deficits and molecular investigations showed that, STIM proteins were decreased in Alzheimer's model, and increased after IN CEPO-FC treatment. Calbindin and PSD-95 were downregulated in our disease model and upregulated when treated with IN CEPO-FC. While Neuroplastin, and GAP-43 expressions remained unchanged. This study suggests that IN CEPO-FC in low doses could be promising for improving cognition and synaptic plasticity deficits in Alzheimer's disease and since IN route of administration is a convenient way, choosing IN CEPO-FC for clinical trial might worth consideration. See also the graphical abstract(Fig. 1).
PubMed: 38741725
DOI: 10.17179/excli2023-6818 -
Experimental Neurobiology Apr 2024In the auditory system, the spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from inner supporting cells (ISCs). This ATP...
In the auditory system, the spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from inner supporting cells (ISCs). This ATP release sets off a cascade, activating purinergic autoreceptors, opening of Ca-activated Cl channel TMEM16A, Cl efflux and osmotic cell shrinkage. Then, the shrunken ISCs efficiently regain their original volume, suggesting the existence of mechanisms for refilling Cland K, priming them for subsequent activity. This study explores the potential involvement of NKCCs (Na-K-Cl cotransporters) and KCCs (K-Cl cotransporters) in ISC spontaneous activity, considering their capability to transport both Cl and K ions across the cell membrane. Employing a combination of immunohistochemistry, pharmacological interventions, and shRNA experiment, we unveiled the pivotal role of NKCC1 in cochlear spontaneous activity. Immunohistochemistry revealed robust NKCC1 expression in ISCs, persisting until the 2nd postnatal week. Intriguingly, we observed a developmental shift in NKCC1 expression from ISCs to synaptophysin-positive efferent terminals at postnatal day 18, hinting at its potential involvement in modulating synaptic transmission during the post-hearing period. Experiments using bumetanide, a well-known NKCC inhibitor, supported the functional significance of NKCC1 in ISC spontaneous activity. Bumetanide significantly reduced the frequency of spontaneous extracellular potentials (sEP) and spontaneous optical changes (sOCs) in ISCs. NKCC1-shRNA experiments conducted in cultured cochlear tissues further supported these findings, demonstrating a substantial decrease in event frequency and area. Taken together, we revealed the role of NKCC1 in shaping the ISC spontaneous activity that govern auditory pathway development.
PubMed: 38724477
DOI: 10.5607/en24003 -
Pharmacological Reports : PR Jun 2024Synthetic cathinones (SC) constitute the second most frequently abused class of new psychoactive substances. They serve as an alternative to classic psychostimulatory...
BACKGROUND
Synthetic cathinones (SC) constitute the second most frequently abused class of new psychoactive substances. They serve as an alternative to classic psychostimulatory drugs of abuse, such as methamphetamine, cocaine, or 3,4-methylenedioxymethamphetamine (MDMA). Despite the worldwide prevalence of SC, little is known about their long-term impact on the central nervous system. Here, we examined the effects of repeated exposure of mice during infancy, to 3,4-methylenedioxypyrovalerone (MDPV), a SC potently enhancing dopaminergic neurotransmission, on learning and memory in young adult mice.
METHODS
All experiments were performed on C57BL/6J male and female mice. Animals were injected with MDPV (10 or 20 mg/kg) and BrdU (bromodeoxyuridine, 25 mg/kg) during postnatal days 11-20, which is a crucial period for the development of their hippocampus. At the age of 12 weeks, mice underwent an assessment of various types of memory using a battery of behavioral tests. Afterward, their brains were removed for detection of BrdU-positive cells in the dentate gyrus of the hippocampal formation with immunohistochemistry, and for measurement of the expression of synaptic proteins, such as synaptophysin and PSD95, in the hippocampus using Western blot.
RESULTS
Exposure to MDPV resulted in impairment of spatial working memory assessed with Y-maze spontaneous alternation test, and of object recognition memory. However, no deficits in hippocampus-dependent spatial learning and memory were found using the Morris water maze paradigm. Consistently, hippocampal neurogenesis and synaptogenesis were not interrupted. All observed MDPV effects were sex-independent.
CONCLUSIONS
MDPV administered repeatedly to mice during infancy causes learning and memory deficits that persist into adulthood but are not related to aberrant hippocampal development.
Topics: Animals; Benzodioxoles; Synthetic Cathinone; Mice; Female; Male; Mice, Inbred C57BL; Pyrrolidines; Memory Disorders; Hippocampus; Maze Learning; Central Nervous System; Memory
PubMed: 38722542
DOI: 10.1007/s43440-024-00599-0 -
Brain and Behavior May 2024Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in...
INTRODUCTION
Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown.
METHODS
In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting.
RESULTS
The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels.
CONCLUSIONS
These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.
Topics: Animals; Melatonin; Sleep Deprivation; Mice; Male; Hippocampus; Female; Memory Disorders; Neuronal Plasticity; Inflammation; Pregnancy; Maternal Deprivation; Cognitive Dysfunction; Prenatal Exposure Delayed Effects; Brain-Derived Neurotrophic Factor; Neuroinflammatory Diseases
PubMed: 38702895
DOI: 10.1002/brb3.3515 -
Journal of Medical Biochemistry Apr 2024Mammography, used for breast cancer (BC) screening, has limitations such as decreased sensitivity in dense breasts. Currently used tumor markers are insufficient in...
BACKGROUND
Mammography, used for breast cancer (BC) screening, has limitations such as decreased sensitivity in dense breasts. Currently used tumor markers are insufficient in diagnosing breast cancer. In this study, we aimed to investigate the relationship between serum levels of synaptophysin-like protein 1 (SYPL1) and BC and compare SYPL1 with other blood tumor markers.
METHODS
The study group consisted of 80 female patients with a histopathological diagnosis of invasive BC who received no radiotherapy/chemotherapy. The control group was 72 women with no previous history of breast disease and evaluated as Breast Imaging Reporting and Data Systems (BI-RADS 1-2) on imaging. Serum SYPL1, cancer antigen 15-3 (CA 15-3), and carcinoembryonic antigen (CEA) were measured in both groups.
PubMed: 38699696
DOI: 10.5937/jomb0-46198 -
Journal of Medical Case Reports May 2024Melanotic neuroectodermal tumor of infancy (MNTI) is a rare clinically benign, pigmented, tumor of neural crest origin which commonly occurs in the maxilla. It is a rare...
BACKGROUND
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare clinically benign, pigmented, tumor of neural crest origin which commonly occurs in the maxilla. It is a rare tumor that may pose difficulty in differentiating from other malignant round cell tumors.
CASE PRESENTATION
A 5-month-old Ethiopian infant presented with a mass on his forehead. A wide excision of the lesion was done and subjected to histopathologic evaluation. The histologic and immunohistochemistry for synaptophysin studies confirmed that the infant was having MNTI. The patient was followed and there was no sign of recurrence at the 6th and 9th months of follow-up.
CONCLUSION
MNTI should be considered as a differential diagnosis for tumors occurring in the head region in infants and prolonged follow-up may be needed to check for possible recurrence of the tumor.
Topics: Humans; Neuroectodermal Tumor, Melanotic; Infant; Male; Diagnosis, Differential; Forehead; Treatment Outcome
PubMed: 38693549
DOI: 10.1186/s13256-024-04550-y -
Brain and Behavior May 2024The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep...
BACKGROUND
The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown.
METHODS
Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines.
RESULTS
SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice.
CONCLUSION
Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.
Topics: Animals; Mice; Sleep Deprivation; Oligopeptides; Male; Mitochondria; Mice, Inbred C57BL; Antioxidants; Hippocampus; Memory Disorders; Cognitive Dysfunction; Sirtuin 1; Disease Models, Animal
PubMed: 38688894
DOI: 10.1002/brb3.3508 -
Journal of Integrative Neuroscience Apr 2024Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1)...
BACKGROUND
Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD.
METHODS
A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1.
RESULTS
Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin.
CONCLUSION
Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.
Topics: Animals; Male; Mice; Amygdala; Anxiety; Anxiety Disorders; Behavior, Animal; Chronic Pain; Depression; Depressive Disorder; Disease Models, Animal; Disks Large Homolog 4 Protein; Homer Scaffolding Proteins; Membrane Proteins; Mice, Inbred C57BL; Nerve Tissue Proteins; Neuralgia; Synaptophysin
PubMed: 38682225
DOI: 10.31083/j.jin2304082 -
Frontiers in Oncology 2024Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant...
Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant literatures. We encountered a 15-year-old boy with a history of hypertension for almost 2 years, accompanied with headache and palpitations. His serum and urine catecholamines were elevated, but no adrenal lesions were detected, suggesting the existence of PGL. Upon physical examination, a painless nodule adherent to the spermatic cord in the right scrotum was found. A systemic Ga DOTATATE PET-CT was then performed, and it revealed a mass with high DOTATATE uptake in the right scrotum. The CT, MRI, and ultrasound images showed the abundant blood supply to the tumor. Based on the above-mentioned imaging and biochemical information, a diagnosis of PGL was made prior to surgery. After 2 weeks of preparation with Cardura, an open surgery was performed to remove the tumor together with the right testis and right epididymis. The blood pressure increased to 180/100 mmHg when the tumor was touched intraoperatively and decreased to 90/55 mmHg after the tumor was removed. Post-operative pathology confirmed our diagnosis of PGL originating from the spermatic cord. Immunohistochemical (IHC) staining showed SDHB (+), CgA (+), synaptophysin (+), GATA3 (+), CD56 (+), sertoli cells S-100 (+), and Ki67 (5%). Genetic testing revealed a missense mutation in the SDHA gene. Only 16 cases of spermatic cord PGL have been reported to date. Although it is easy to diagnose by histology and IHC examinations, preoperative diagnosis is quite important as it can actually reduce intraoperative complications.
PubMed: 38680861
DOI: 10.3389/fonc.2024.1373727