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Heliyon Apr 2024Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of...
Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both and . Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.
PubMed: 38655332
DOI: 10.1016/j.heliyon.2024.e29481 -
Biology of Sex Differences Apr 2024The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals,...
BACKGROUND
The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals, integrating emotional information, and regulating related behaviors. The cells in the LHb are predominantly glutamatergic and have heterogeneous functions in response to different stimuli. The circuitry connections of the LHb glutamatergic neurons play a crucial role in integrating a wide range of events. However, the circuitry connections of LHb glutamatergic neurons in both sexes have not been thoroughly investigated.
METHODS
In this study, we injected Cre-dependent retrograde trace virus and anterograde synaptophysin-labeling virus into the LHb of adult male and female Vglut2-ires-Cre mice, respectively. We then quantitatively analyzed the input and output of the LHb glutamatergic connections in both the ipsilateral and contralateral whole brain.
RESULTS
Our findings showed that the inputs to LHb neurons come from more than 30 brain subregions, including the cortex, striatum, pallidum, thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum with no significant differences between males and females. The outputs of LHb neurons targeted eight large brain regions, primarily focusing on the midbrain and pons nuclei, with distinct features in presynaptic bouton across different brain subregions. While correlation and cluster analysis revealed differences in input and collateral projection features, the input-output connection pattern of LHb neurons in both sexes was highly similar.
CONCLUSIONS
This study provides a systematic and comprehensive analysis of the input and output connections of LHb neurons in male and female mice, shedding light on the anatomical architecture of these specific cell types in the mouse LHb. This structural understanding can help guide further investigations into the complex functions of the LHb.
Topics: Animals; Female; Male; Habenula; Neurons; Sex Characteristics; Glutamic Acid; Vesicular Glutamate Transport Protein 2; Neural Pathways; Mice
PubMed: 38654275
DOI: 10.1186/s13293-024-00611-5 -
Open Veterinary Journal Jan 2024Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
BACKGROUND
Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
AIM
An important objective of this work was to give a full account of the clinical, pathological, and immune-histochemical features of several skin tumors in dogs.
METHODS
This study was a case series in the hospital clinic, Faculty of Veterinary Medicine, Zagazig University, Egypt. Twenty-five dogs (14 males and 11 females) were examined clinically during the period from March 2022 to October 2023. The skin swelling was collected from affected animals and then subjected to a detailed histopathological study to record the different gross and microscopic findings and confirm the diagnosis by immunohistochemistry.
RESULTS
Skin neoplasia in dogs was exposed to various clinical signs, and the dogs' ages ranged between 3 and 11 years. Concerning tumor features, the majority of neoplasms were malignant (65.52%) more than benign (34.48%). The study revealed the presence of 29 cases of dogs showed neoplasia with different prevalence rates including squamous cell carcinoma (13.79%), mast cell tumor (6.89%), basal cell tumors (10.34%), histiocytoma (6.89%), trichoepithelioma (10.34%), transmissible venereal tumor (10.34%), trichilemmoma (3.44%), scalp paraganglioma (3.44%), pilomatricoma (10.34%), malignant melanomas (17.24%), and miscellaneous cases as fat necrosis (6.89%), in males and females dogs with different histopathological lesions and immunohistochemistry expressions for pan-cytokeratin (CK), melanocyte-differentiation antigens (S100 protein), and synaptophysin.
CONCLUSION
Malignant melanomas (17.24%) are the extremely common cutaneous tumors diagnosed in this study. Meanwhile, benign tumors such as trichilemmoma, trichoepithelioma, pilomatricoma, and paraganglioma are less frequent in dogs.
Topics: Humans; Male; Female; Dogs; Animals; Melanoma; Pilomatrixoma; Egypt; Skin Neoplasms; Paraganglioma; Mammals; Dog Diseases
PubMed: 38633166
DOI: 10.5455/OVJ.2024.v14.i1.44 -
Surgical Case Reports Apr 2024A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the...
CASE PRESENTATION
A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the duodenum. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion in the descending part of the duodenum. Endoscopic ultrasound revealed a well-defined hypoechoic tumor. Biopsy and immunohistochemical findings including negative Synaptophysin and Chromogranin A staining and positive Trypsin and BCL10 staining suggested a carcinoma with acinar cell differentiation. Pancreatoduodenectomy was performed, and the resected specimen had a 15-mm solid nodule in the submucosal layer of the duodenum. Pancreatogram of the resected specimen revealed a tumor localized in the accessory papilla region. In histopathological examination, the tumor was found in the submucosa of the duodenum with pancreatic tissue present nearby, and these were separated from the pancreatic parenchyma by the duodenal muscle layer. These findings led to a diagnosis of acinar cell carcinoma originating from the accessory papilla of the duodenum.
CONCLUSION
Acinar cell carcinoma originating from the accessory papilla of the duodenum is exceptionally rare, with no reported cases to date. The origin was considered to be pancreatic tissue located in the accessory papilla region.
PubMed: 38625458
DOI: 10.1186/s40792-024-01872-3 -
Iranian Journal of Child Neurology 2024Diabetes mellitus during pregnancy is a common complication of gestation, but its effects on the offspring's development are poorly understood. Recently, some studies... (Review)
Review
Diabetes mellitus during pregnancy is a common complication of gestation, but its effects on the offspring's development are poorly understood. Recently, some studies reported that gestational diabetes mellitus (GDM) impairs cerebellar development, and some genetic alterations have been described as consequences. Cerebellum, one of the hindbrain derived structures in the posterior cranial fossa, plays a crucial role in cognition and behavioral functions. In recent years, some surveys stated that gestational diabetes has adverse effects on the fetus's cerebellum. Disruption of cerebellar cortex morphogenesis, reduce the volume of the cerebellum, reduce the thickness of cerebellar cortex layers, and its neuronal cells and effects on the expression of synaptophysin, insulin, and insulin-like growth factor -1 receptors are some of the maternal diabetes effects on developing cerebellum. On other hand, GDM, as a neurotoxic agent, impaired cerebellar development and could be a cause for the behavioral, functional, and structural anomalies observed in pups of diabetic mothers. Based on the literature review, most studies have pointed out that administering insulin in patients with GDM decreased the cellular and molecular alterations that induced by GDM in the developing cerebellum. Undoubtedly, screening strategies for all pregnant women are necessary.
PubMed: 38617398
DOI: 10.22037/IJCN.V18I2.36632 -
Neurobiology of Stress May 2024The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid...
The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity and , such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.
PubMed: 38601361
DOI: 10.1016/j.ynstr.2024.100632 -
Frontiers in Pharmacology 2024Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Due to the multifactorial nature of the disease,...
Pharmacological enhancement of cholinergic neurotransmission alleviates neuroinflammation and improves functional outcomes in a triple transgenic mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Due to the multifactorial nature of the disease, involving impairment of cholinergic neurotransmission and immune system, previous attempts to find effective treatments have faced challenges. In such scenario, we attempted to investigate the effects of alpha-glyceryl-phosphoryl-choline (α-GPC), a cholinomimetic molecule, on neuroinflammation and memory outcome in the triple transgenic mouse model of AD (3xTg-AD). Mice were enrolled at 4 months of age, treated orally with α-GPC dissolved in drinking water at a concentration resulting in an average daily dose of 100 mg/kg for 8 months and sacrificed at 12 months of age. Thereafter, inflammatory markers, as well as cognitive parameters, were measured. Chronic α-GPC treatment reduced accumulation of amyloid deposits and led to a substantial re-balance of the inflammatory response of resident innate immune cells, astrocytes and microglia. Specifically, fluorescent immunohistochemistry and Western blot analysis showed that α-GPC contributed to reduction of cortical and hippocampal reactive astrocytes and pro-inflammatory microglia, concurrently increasing the expression of anti-inflammatory molecules. Whereas α-GPC beneficially affect the synaptic marker synaptophysin in the hippocampus. Furthermore, we observed that α-GPC was effective in restoring cognitive dysfunction, as measured by the Novel Object Recognition test, wherein 3xTg-AD mice treated with α-GPC significantly spent more time exploring the novel object compared to 3xTg-AD untreated mice. In conclusion, chronic treatment with α-GPC exhibited a significant anti-inflammatory activity and sustained the key function of hippocampal synapses, crucial for the maintenance of a regular cognitive status. In light of our results, we suggest that α-GPC could be exploited as a promising therapeutic approach in early phases of AD.
PubMed: 38595916
DOI: 10.3389/fphar.2024.1386224 -
Brain Research Jun 2024Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new...
Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway.
Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new brain-protective medication developed in China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with a need for additional research to elucidate its role and mechanisms in VD contexts. In a research setup, a VD model was established utilizing Sprague-Dawley (SD) rats, subjected to permanent bilateral typical carotid artery occlusion (2VO). Behavioral assessment of the rats was conducted using the Bederson test and pole climbing test, while cognitive abilities, particularly learning and memory, were evaluated via the novel object recognition test and the Morris water maze test. Ensuing, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), IL-1β, IL-6, IL-4, and tumor necrosis factor-α (TNF-α) were determined through Enzyme-Linked Immunosorbent Assay (ELISA). Synaptic plasticity-related proteins, synaptophysin (SYP), post-synaptic density protein 95 (PSD-95), and N-methyl-D-aspartate (NMDA) receptor proteins (NR1, NR2A, NR2B) were investigated via Western blotting technique. The findings imply that EDB has the potential to ameliorate cognitive deficiencies, attributed to VD, by mitigating oxidative stress, dampening inflammatory responses, and modulating the NMDA receptor signaling pathway, furnishing new perspectives into EDB's mechanism and proposing potential avenues for therapeutic strategies in managing VD.
Topics: Animals; Dementia, Vascular; Oxidative Stress; Rats, Sprague-Dawley; Edaravone; Cognitive Dysfunction; Rats; Hippocampus; Receptors, N-Methyl-D-Aspartate; Male; Signal Transduction; Disease Models, Animal; Neuroprotective Agents; Inflammation
PubMed: 38582415
DOI: 10.1016/j.brainres.2024.148917 -
Scientific Reports Apr 2024Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying...
Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.
Topics: Mice; Animals; Liraglutide; Sodium Chloride, Dietary; Glucagon-Like Peptide-1 Receptor; Sodium Chloride; Ribosomal Protein S6 Kinases, 70-kDa; Mice, Inbred C57BL; Signal Transduction; Cognitive Dysfunction; TOR Serine-Threonine Kinases; Cognition
PubMed: 38575652
DOI: 10.1038/s41598-024-57998-9 -
Case Reports in Obstetrics and... 2024Primary ovarian carcinoid tumors (POCT) are well-differentiated neuroendocrine neoplasms and account for <0.1% of ovarian tumors. POCT usually arise in the context of...
Primary ovarian carcinoid tumors (POCT) are well-differentiated neuroendocrine neoplasms and account for <0.1% of ovarian tumors. POCT usually arise in the context of mature cystic teratoma; however, pure primary ovarian carcinoids without teratomatous or mucinous elements are very rare. We present a case of a 54-year-old woman that underwent total laparoscopic hysterectomy and bilateral salpingo-oophorectomy because of endometrial hyperplasia without atypia. The ovaries were macroscopically normal. Pathology report revealed a primary ovarian carcinoid with mixed trabecular and insular growth patterns. Immunohistochemical was positive for chromogranine A, synaptophysin, and CDX2. The Ki-67 index was <1%. To exclude a metastatic carcinoid to the ovary, a Ga-68 PET/CT was performed. This case highlights the microscopic and immunohistochemical characteristics of pure POCT and potential pitfalls in their differentiation from metastatic carcinoids. In addition, differential characteristics of primary and metastatic ovarian carcinoids are discussed.
PubMed: 38572183
DOI: 10.1155/2024/5890300