Genetic ablation of Saposin ‐D in Krabbe disease eliminates psychosine accumulation but does not significantly improve demyelination
In this study, we generated Twi mice with a Sap-D deficiency (Twi/Sap-D KO), which are genetically deficient in both GALC and Sap-D and found that very little psychosine accumulated in the CNS or PNS of the mouse. As expected, demyelination with the infiltration of multinucleated macrophages (globoid cells) characteristic of Krabbe disease was milder in Twi/Sap-D KO mice than in Twi mice both in the CNS and PNS during the early disease stage. However, at the later disease stage, qualitatively and quantitatively comparable demyelination occurred in Twi/Sap-D KO mice, particularly in the PNS, and the lifespans of Twi/Sap-D K...
Source: Journal of Neurochemistry - June 20, 2023 Category: Neuroscience Authors: Takashi Watanabe,
Kazuhito Tsuboi,
Nobuaki Matsuda,
Yuta Ishizuka,
Shinji Go,
Etsuko Watanabe,
Ayaka Ono,
Yasuo Okamoto,
Junko Matsuda Tags: ORIGINAL ARTICLE Source Type: research
Cerebrospinal fluid, brain, and spinal cord levels of L ‐aspartate signal excitatory neurotransmission abnormalities in multiple sclerosis patients and experimental autoimmune encephalomyelitis mouse model
Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by inflammation, demyelination, gliosis, and neurodegeneration in the central nervous system. Neuroinflammatory processes in MS are associated with a remarkable overactivation of glutamate receptors; however, the specific involvement of excitatory amino acid levels remains unclear. In a cohort of relapsing –remitting MS patients but not controls, we showed a marked correlation between the cerebrospinal fluid (CSF) levels of the endogenous NMDA receptor agonist, L-aspartate, and those of the cytokines G-CSF, IL-1ra, MIP-1β, and Eotaxin. These find...
Source: Journal of Neurochemistry - June 19, 2023 Category: Neuroscience Authors: Francesco Errico,
Luana Gilio,
Andrea Mancini,
Tommaso Nuzzo,
Mario Stampanoni Bassi,
Laura Bellingacci,
Fabio Buttari,
Ettore Dolcetti,
Antonio Bruno,
Giovanni Galifi,
Roberto Furlan,
Annamaria Finardi,
Anna Di Maio,
Massimiliano Di Filip Tags: ORIGINAL ARTICLE Source Type: research
Modulation of the autophagy ‐lysosomal pathway and endoplasmic reticulum stress by ketone bodies in experimental models of stroke
We report for the first time that the protective effect of β-hydroxybutyrate (BHB) against stroke and glucose deprivation is enantiomer selective. We discovered that D-BHB treatment prevented the cleavage of the lysosomal membrane protein LAMP2, maintained lysosome integrity and stimulated the autophagic flux. Also, D-BHB notably reduced the activation of the PERK and IRE1α branches of the unfolded protein response (UPR), attenuating protein synthesis inhibition and preventing endoplasmic reticulum stress. Together our results support the therapeutic use of D-BHB treatment post-ischemia, by preventing the loss of proteos...
Source: Journal of Neurochemistry - June 17, 2023 Category: Neuroscience Authors: Teresa Montiel,
Juan Carlos G ómora‐García,
Cristian Gerónimo‐Olvera,
Yessica Heras‐Romero,
Berenice N. Bernal‐Vicente,
Xochitl Pérez‐Martínez,
Luis B. Tovar‐y‐Romo,
Lourdes Massieu Tags: ORIGINAL ARTICLE Source Type: research
Single ‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination
Using single-cell RNA sequencing, we examined the transcriptional profiles and intercellular communication of Schwann cells in the high-fat diet-fed mouse, a model of prediabetic neuropathy. We show that myelinating Schwann cells acquire a unique transcriptional profile secondary to prediabetes. We also demonstrate a shift in cellular communication, which impacts nonmyelinating Schwann cell integrity, function, and the inflammatory response. Validation analyses shows that neuropathic Schwann cells become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study constitutes a valuable resource ...
Source: Journal of Neurochemistry - June 17, 2023 Category: Neuroscience Authors: St éphanie A. Eid,
Mohamed Noureldein,
Bhumsoo Kim,
Lucy M. Hinder,
Faye E. Mendelson,
John M. Hayes,
Junguk Hur,
Eva L. Feldman Tags: ORIGINAL ARTICLE Source Type: research
Innovations advancing our understanding of microglia in Alzheimer's disease: From in vitro to in vivo models
Microglial research has been limited because of poor conservation of microglial states across species, and in vitro models having distinct transcriptomic profiles to native microglia in vivo. Advances in technologies, such as single-cell RNA sequencing, have allowed for a deeper understanding of microglial heterogeneity in healthy states and neurodegeneration. The transplantation of microglia derived from human pluripotent stem cells into organoids or mouse brains better mimics the 3D physiological microenvironment, allowing for restoration of morphology and phenotypic states similar to native microglia. Xenotransplantatio...
Source: Journal of Neurochemistry - June 16, 2023 Category: Neuroscience Authors: Simon Maksour,
Lezanne Ooi Tags: REVIEW Source Type: research
Cross ‐talk between DNA damage response and the central carbon metabolic network underlies selective vulnerability of Purkinje neurons in ataxia‐telangiectasia
Cerebellar ataxia, the first and irreversible outcome in ataxia-telangiectasia (A-T), is caused by selective Purkinje neuronal degeneration. A-T results from mutations of the ataxia-telangiectasia –mutatedATM gene. Functional ATM is involved in regulating both DNA damage response and fuel metabolic network. The key question that arose is how Purkinje neurons become selectively vulnerable when other brain cells are suffering from the very same genetic mutations. Here, unexpected cross-talks between these two seemingly independent cellular functions and the regulatory roles of ATM are elaborated. Together with the unique p...
Source: Journal of Neurochemistry - June 15, 2023 Category: Neuroscience Authors: Jacquelyne Ka ‐Li Sun,
Genper Chi‐Ngai Wong,
Kim Hei‐Man Chow Tags: REVIEW Source Type: research
C9orf72 poly ‐PR helps p53 escape from the ubiquitin‐proteasome system and promotes its stability
In this study, we verify whether C9orf72 PR enhances p53 stability and activity by interfering with p53 degradation and ubiquitination modifications, which shed new light on the pathogenesis of C9orf72 poly(PR)-related ALS/FTD. AbstractC9orf72-derived dipeptide repeats (DPRs) proteins have been regarded as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). As the most toxic DPRs in C9-ALS/FTD, poly-proline-arginine (poly-PR) is associated with the stability and accumulation of p53, which consequently induces neurodegeneration. However, the exact molecular me...
Source: Journal of Neurochemistry - June 15, 2023 Category: Neuroscience Authors: Fumin Yang,
Yacoubou Abdoul Razak Mahaman,
Bin Zhang,
Jian ‐Zhi Wang,
Rong Liu,
Fei Liu,
Xiaochuan Wang Tags: ORIGINAL ARTICLE Source Type: research
Functional principles of genetically encoded fluorescent biosensors for metabolism and their quantitative use
Quantitative biosensing requires a direct relationship between the measured fluorescence output and changes in metabolite levels. Interferences such as from pH, temperature or other molecules can produce fluorescence changes even when metabolite levels are constant, presenting a challenge for quantitation. This review describes current methods of fluorescent biosensor quantitation, with a focus on cellular interferences that commonly affect sensor performance, ways to avoid false inferences, and recent advances in sensor optimization to make them more robust. AbstractGenetically encoded fluorescent biosensors provide an at...
Source: Journal of Neurochemistry - June 15, 2023 Category: Neuroscience Authors: Dorothy Koveal Tags: REVIEW Source Type: research
Toward discovering a novel family of peptides targeting neuroinflammatory states of brain microglia and astrocytes
Microglia are critical to the development and healthy function of the brain and spinal cord, yet are implicated in the active pathology of many neuropsychiatric disorders. Here we proposed in vitro models for surveying, reactive, and primed sub-types of primary rat microglia and mixed microglia/astrocytes. We used a custom 7 amino acid-presenting M13 phage display library (SX7) to discover 58 unique peptides binding to these phenotypes across both glial types and characterized their potential basic local alignment search tool origin. We believe these findings should provide a framework for investigating new biomarkers and ...
Source: Journal of Neurochemistry - June 14, 2023 Category: Neuroscience Authors: K. M. Koss,
T. Son,
C. Li,
Y. Hao,
J. Cao,
M. A. Churchward,
Z. J. Zhang,
J. A. Wertheim,
R. Derda,
K. G. Todd Tags: ORIGINAL ARTICLE Source Type: research
METTL14 is decreased and regulates m6A modification of α‐synuclein in Parkinson's disease
This study provides novel evidence that the levels of m6A were significantly decreased in the peripheral blood of Parkinson's disease, and METTL14 was the main factor involved in abnormal m6A modification, and has the potential to be a novel diagnostic biomarker for PD. Mechanism experiments showed that METTL14 catalyze the m6A modification on α-syn mRNA through binding to the m6A motif in the CDS regions of α-syn mRNA, and need YTHDF2 recognizing m6A -modified α-syn mRNA to promote α-syn degradation. AbstractN6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological pro...
Source: Journal of Neurochemistry - June 14, 2023 Category: Neuroscience Authors: Honghu He,
Qinxin Zhang,
Jiajia Liao,
Jiang Lei,
Man Luo,
Jianyi Huang,
Meiling Chen,
Yuefei Shen,
Jin Wang,
Pingyi Xu,
Yousheng Xiao Tags: ORIGINAL ARTICLE Source Type: research
Toll ‐like receptor 4‐mediated microglial inflammation exacerbates early white matter injury following experimental subarachnoid hemorrhage
In conclusion, microglial inflammation has dual effects on early WMI after experimental SAH. Future explorations on more clinically relevant methods for modulating neuroinflammation are warranted to combat stroke with both WMI and gray matter destruction. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - June 13, 2023 Category: Neuroscience Authors: Jianhua Peng,
Yuke Xie,
Jinwei Pang,
Yue Wu,
Jian Zhou,
Long Gu,
Kecheng Guo,
Lifang Zhang,
Bingqing Xie,
Shigang Yin,
Xiaochuan Sun,
Ligang Chen,
Yong Jiang Tags: ORIGINAL ARTICLE Source Type: research
Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations
In conclusion, lactate is less effective than glucose and potentially detrimental during neural network rhythms featuring high energetic costs, likely thr ough the lack of some obligatory ATP synthesis by aerobic glycolysis at excitatory and inhibitory synapses. High lactate/glucose ratios might contribute to central fatigue, cognitive impairment, and epileptic seizures partially seen, for instance, during exhaustive physical exercise, hypoglycemia an d neuroinflammation. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - June 13, 2023 Category: Neuroscience Authors: Oliver Kann Tags: REVIEW Source Type: research
Neurotensin and energy balance
The neurotensin system spans across the central nervous system, to the enteric nervous system (gut), and the periphery to govern behaviors and physiological responses that tune energy balance to maintain homeostasis. Neurotensin transmission is not only modulated by metabolic signals, neurotensin transmission itself can also impact metabolic state by exerting control over consumption, physical activity, and satiety signals. Many responses to sensory experiences and sleep processes are dictated by neurotensinergic activity via mechanisms that allow the organism to balance energy seeking and utilization to thrive in its envi...
Source: Journal of Neurochemistry - June 13, 2023 Category: Neuroscience Authors: Graydon B. Gereau,
Sy ’Keria D. Garrison,
Zoe A. McElligott Tags: REVIEW Source Type: research
Proteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric A β
This study revealed differential secretion of proteins involved in the extracellular matrix and cytoskeletal organization, changes in the response to oxidative stress, and increased secretion of proteins with chaperone activity. AbstractAstrocytes associate with amyloid plaques in Alzheimer's disease (AD). Astrocytes react to changes in the brain environment, including increasing concentrations of amyloid- β (Aβ). However, the precise response of astrocytes to soluble small Aβ oligomers at concentrations similar to those present in the human brain has not been addressed. In this study, we exposed astrocytes to media fro...
Source: Journal of Neurochemistry - June 12, 2023 Category: Neuroscience Authors: Vittoria Matafora,
Alena Gorb,
Fangjia Yang,
Wendy Noble,
Angela Bachi,
Beatriz Gomez Perez ‐Nievas,
Maria Jimenez‐Sanchez Tags: ORIGINAL ARTICLE Source Type: research
Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating fat mass and obesity ‐associated—N6‐methyladenosine—acyl‐CoA synthetase long‐chain family member 4 axis
Ischemic stroke (IS) is a detrimental neurological disease with limited treatments options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. In our study, As-IV promoted the transcription of fat mass and obesity-associated (Fto) by upregulating activating transcription factor 3(Atf3), resulting in a decrease of long-chain acyl-CoA synthetase-4 (Acsl4) N6-methyladenosine (m6A) levels, thus improving neuronal injury in IS by inhibiting ferroptosis. These findings provided a better understanding of the molecular mechanisms underlying the neuroprotective effects of As-IV and led to novel t...
Source: Journal of Neurochemistry - June 10, 2023 Category: Neuroscience Authors: Zhenglong Jin,
Wenying Gao,
Fu Guo,
Shaojun Liao,
Mingzhe Hu,
Tao Yu,
Shangzhen Yu,
Qing Shi Tags: ORIGINAL ARTICLE Source Type: research
