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Brain Sciences Mar 2024Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent...
Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse's hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders.
PubMed: 38671979
DOI: 10.3390/brainsci14040327 -
Veterinary Sciences Apr 2024A 13-month-old, neutered, male, domestic shorthair cat was referred with a history of progressive paraparesis, proprioceptive ataxia, and lumbar spinal pain....
A 13-month-old, neutered, male, domestic shorthair cat was referred with a history of progressive paraparesis, proprioceptive ataxia, and lumbar spinal pain. Neurological examination revealed non-ambulatory paraparesis consistent with L4-S1 myelopathy. Magnetic resonance of the thoracolumbar spinal cord identified a dorsal intradural extramedullary space-occupying lesion extending from L5 to L6. It was homogeneously hyperintense in T2-weighted imaging and isointense in T1-weighted imaging and exhibited marked and homogeneous contrast enhancement in the T1-weighted post-contrast imaging. The removed tissue was composed of neoplastic cells arranged as pseudostratified or multilayered trabecular and tubular structures, supported by internal and external limiting PAS-positive membranes. The neoplastic cells were immunoreactive for vimentin and NSE and negative for GFAP, Olig2, synaptophysin, PCK, S-100, NeuN, and nestin. The Ki-67 nuclear labeling index was up to 90%. The tumor was consistent with the diagnosis of medulloepithelioma, which is most frequently reported as an intraocular tumor. The morphological and immunohistochemical features of the tumor showed remarkable concordance with most human medulloepitheliomas. This is the first spinal cord medullopethelioma report in a cat, with the clinical, neuroradiological, histological, and immunohistochemical findings being described.
PubMed: 38668444
DOI: 10.3390/vetsci11040177 -
Frontiers in Synaptic Neuroscience 2024Rapid, synapse-specific neurotransmission requires the precise alignment of presynaptic neurotransmitter release and postsynaptic receptors. How postsynaptic glutamate...
Rapid, synapse-specific neurotransmission requires the precise alignment of presynaptic neurotransmitter release and postsynaptic receptors. How postsynaptic glutamate receptor accumulation is induced during maturation is not well understood. We find that in cultures of dissociated hippocampal neurons at 11 days (DIV) numerous synaptic contacts already exhibit pronounced accumulations of the pre- and postsynaptic markers synaptotagmin, synaptophysin, synapsin, bassoon, VGluT1, PSD-95, and Shank. The presence of an initial set of AMPARs and NMDARs is indicated by miniature excitatory postsynaptic currents (mEPSCs). However, AMPAR and NMDAR immunostainings reveal rather smooth distributions throughout dendrites and synaptic enrichment is not obvious. We found that brief periods of Ca influx through NMDARs induced a surprisingly rapid accumulation of NMDARs within 1 min, followed by accumulation of CaMKII and then AMPARs within 2-5 min. Postsynaptic clustering of NMDARs and AMPARs was paralleled by an increase in their mEPSC amplitudes. A peptide that blocked the interaction of NMDAR subunits with PSD-95 prevented the NMDAR clustering. NMDAR clustering persisted for 3 days indicating that brief periods of elevated glutamate fosters permanent accumulation of NMDARs at postsynaptic sites in maturing synapses. These data support the model that strong glutamatergic stimulation of immature glutamatergic synapses results in a fast and substantial increase in postsynaptic NMDAR content that required NMDAR binding to PSD-95 or its homologues and is followed by recruitment of CaMKII and subsequently AMPARs.
PubMed: 38660466
DOI: 10.3389/fnsyn.2024.1291262 -
Cureus Mar 2024I-metaiodobenzylguanidine (I-MIBG) scintigraphy is a highly sensitive and specific imaging test for the diagnosis of pheochromocytoma. Typical pheochromocytomas are...
A Case of Pheochromocytoma With Coagulation Necrosis Due to Hypertensive Crisis Aggravated by Contrast-Enhanced CT Scan and Negative 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy.
I-metaiodobenzylguanidine (I-MIBG) scintigraphy is a highly sensitive and specific imaging test for the diagnosis of pheochromocytoma. Typical pheochromocytomas are positive on I-MIBG scintigraphy; however, cases of paragangliomas eliciting negative results have been reported. We encountered a case of hypertensive crisis resulting in extensive coagulative necrosis of a pheochromocytoma and negative findings on I-MIBG scintigraphy. A 50-year-old Japanese female presented with an acute onset of vomiting, epigastralgia, and abdominal pain. Immediately after contrast-enhanced CT, the patient developed respiratory failure and was intubated. The CT scan revealed a 5-cm left adrenal mass, and a pheochromocytoma crisis was suspected. The patient's condition stabilized following phentolamine administration. Regarding the assessment for pheochromocytoma, plasma metanephrine levels were not markedly increased, and I-MIBG scintigraphy was negative. However, a histological examination of the left adrenal mass revealed extensive coagulative necrosis of the entire adrenal mass, comprising trabecular and alveolar growth of large polygonal cells that were immunopositive for chromogranin A/synaptophysin, thereby suggesting a diagnosis of pheochromocytoma. There have been three reported cases of I-MIBG scintigraphy-negative pheochromocytomas because of pure avascular necrosis without hemorrhage or rupture. To the best of our knowledge, this is the first reported case of massive tumor necrosis due to hypertensive crisis exacerbated after contrast-enhanced CT imaging. In conclusion, pheochromocytoma cannot be ruled out even with negative findings on I-MIBG scintigraphy. Accordingly, clinical judgment must be made based on a comprehensive assessment of the clinical course and pathological diagnosis, especially for cases involving a hypertensive crisis.
PubMed: 38659567
DOI: 10.7759/cureus.56878 -
Clinical Case Reports Apr 2024Laryngeal neuroendocrine carcinomas are the most common non-squamous neoplasm of the larynx. Due to the rarity of the tumor, pathological diagnosis should be confirmed...
KEY CLINICAL MESSAGE
Laryngeal neuroendocrine carcinomas are the most common non-squamous neoplasm of the larynx. Due to the rarity of the tumor, pathological diagnosis should be confirmed by immunohistochemistry.
ABSTRACT
Laryngeal neuroendocrine carcinomas (LNECs) are a rare cancer of the head and neck. Few case reports of poorly differentiated neuroendocrine carcinoma originating in the subglottic larynx exist within the literature. In this case, we discuss a 57-year-old patient with a history of four-month hoarseness with a newly diagnosed of poorly differentiated neuroendocrine carcinoma in the subglottic larynx. Treatment and prognosis of the various NEC groups differ, so precise identification requires consideration of the microscopic findings and immunostaining analysis. immunohistochemistry staining demonstrated positive result for cytokeratin 7, synaptophysin, chromogranin, CD 56, with the Ki-67 index of45%. Although surgery is usually the treatment for all tumor types, chemo radiotherapy is recommended for poorly differentiated NECs because surgery is ineffective.
PubMed: 38659503
DOI: 10.1002/ccr3.8792 -
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