Lysoglycosphingolipids have the ability to induce cell death through direct PI3K inhibition
We propose lysoglycosphingolipids (lysoGSLs) as a cause of neuronal cell death in sphingolipidoses. In sphingolipidoses, glycosphingolipids accumulate excessively in lysosomes and lysoGSLs are generated. These lysoGSLs directly inhibit phosphoinositide 3-kinase (PI3K), suppress downstream PI3K/Akt signaling, and induce apoptotic signaling. Since multiple lysoGSLs cause PI3K inhibition, lysoGSLs are thought to be a common cause of neuronal cell death in sphingolipidoses. This finding suggests a new therapeutic approach to sphingolipidoses, which are extremely difficult to treat. AbstractSphingolipidoses are inherited metabo...
Source: Journal of Neurochemistry - November 18, 2023 Category: Neuroscience Authors: Ryosuke Watanabe,
Daisuke Tsuji,
Hiroki Tanaka,
Michael Shintaro Uno,
Yukiya Ohnishi,
Shindai Kitaguchi,
Tsuyoshi Matsugu,
Ryuto Nakae,
Hiromi Teramoto,
Kei Yamamoto,
Yasuo Shinohara,
Takatsugu Hirokawa,
Nozomu Okino,
Makoto Ito,
Kohji Itoh Tags: ORIGINAL ARTICLE Source Type: research
Non ‐invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by 1H magnetic resonance spectroscopy
Choi et al. present a1H magnetic resonance spectroscopy (MRS) study to delineate the effect of poorly controlled chronic hyperglycemia from type 2 diabetes (T2D) on neurochemical profiles in humans and mice. Brain glucose levels were higher in humans cross-sectionally and animals longitudinally in addition to taurine, glucose+taurine,myo-inositol, and choline-containing compounds compared with controls. Overall, this study demonstrates hyperglycemia-induced changes in neurochemicals that serve a suite of biological functions, including as neurotransmitters, bioenergetic substrates, organic osmolytes, and messenger molecu...
Source: Journal of Neurochemistry - November 16, 2023 Category: Neuroscience Authors: In ‐Young Choi,
Wen‐Tung Wang,
Bhumsoo Kim,
Junguk Hur,
David C. Robbins,
Dae‐Gyu Jang,
Masha G. Savelieff,
Eva L. Feldman,
Phil Lee Tags: ORIGINAL ARTICLE Source Type: research
Induced pluripotent stem cells ‐based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis
Over the past 15 years since the advent of induced pluripotent stem cell (iPSC) technology, interest in its medical applications has steadily increased. We have established iPSCs from patients suffering from various intractable neurological diseases, including amyotrophic lateral sclerosis (ALS). By inducing thei r differentiation into MNs, we analyzed their pathological conditions, carried out drug discovery screenings, and identified Ropinirole hydrochloride as a potential treatment for ALS. Subsequent clinical trials were conducted with this drug. Drawing from these findings, we embarked on reverse transl ational res...
Source: Journal of Neurochemistry - November 13, 2023 Category: Neuroscience Authors: Hideyuki Okano,
Satoru Morimoto,
Chris Kato,
Jin Nakahara,
Shinichi Takahashi Tags: REVIEW Source Type: research
Issue Information
Front coverWe speculate that Trem2 plays a key role in white matter injury induced by chronic hypoperfusion. Trem2 deficiency ameliorated microglial phagocytosis and autophagic-lysosomal activation in hypoperfusion-induced white matter injury, and could be a promising target for the treatment of chronic cerebral hypoperfusion.Image contentTrem2 deficiency attenuates microglial phagocytosis and autophagic-lysosomal activation in white matter hypoperfusion.Read the full article‘Trem2 deficiency attenuates microglial phagocytosis and autophagic-lysosomal activation in white matter hypoperfusion ’ by X.-W. Pang, Y.-H. Chu,...
Source: Journal of Neurochemistry - November 11, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research
Novel single ‐nucleus transcriptomics unravels developmental and functionally controlled principles of mammalian neuromuscular junctions
Motoneurons reach out to muscles, form neuromuscular junctions and release the neurotransmitter acetylcholine at these junctions to ignite their activities. However, which genes are activated to make that happen, and where and when in the course of neuromuscular development do they exert their activities remains incompletely understood. These are the issues handled in the innovative Ohno manuscript. AbstractProf Ohno's team (Ohkawara et al. 2023, current issue) underscored the dynamic and functional features that co-shape the embryonic and early post-natal development of mammalian neuromuscular junctions (NMJs) using singl...
Source: Journal of Neurochemistry - November 10, 2023 Category: Neuroscience Authors: Hermona Soreq Tags: EDITORIAL Source Type: research
Mutations of evolutionarily conserved aromatic residues suggest that misfolding of the mouse prion protein may commence in multiple ways
In this study, using hydrogen exchange and mass spectrometry, we found that the native state of the mouse prion protein is in equilibrium with multiple partially unfolded forms (PUFs) capable of initiating misfolding. Mutating three conserved aromatic residues destabilized the native state and reduced energy differences between the native state and two PUFs. Misfolding can initiate from these distinct PUFs, suggesting multiple pathways for misfolding. Mutant variants significantly increase the population of the PUFs, accelerating misfolding. This implies that the three aromatic residues may have evolved to impede misfoldin...
Source: Journal of Neurochemistry - November 9, 2023 Category: Neuroscience Authors: Suman Pal,
Jayant B. Udgaonkar Tags: ORIGINAL ARTICLE Source Type: research
Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease
In Alzheimer's disease (AD), reactive astrocytes have long been observed in senile plaques and have recently been suggested to play a role in AD pathogenesis and progression. However, the precise contributions of reactive astrocytes to AD remain elusive, and targeting this complex cell population for AD treatment poses significant challenges. In this review, we summarize the current understanding of astrocyte reactivity and its role in AD, with a particular focus on the signaling pathways that promote astrocyte reactivity and the heterogeneity of reactive astrocytes. Furthermore, we explore potential implications for the d...
Source: Journal of Neurochemistry - November 7, 2023 Category: Neuroscience Authors: Hongwei Qin,
Lianna Zhou,
Faris T. Haque,
Cynthia Martin ‐Jimenez,
Amy Trang,
Etty N. Benveniste,
Qin Wang Tags: REVIEW Source Type: research
The dentate gyrus differentially metabolizes glucose and alternative fuels during rest and stimulation
Stable isotope tracing in acute hippocampal slices followed by mass spectrometry imaging reveals DGC layer metabolism of alternative fuels, including lactate/pyruvate and β-hydroxybutyrate (βHB), into the TCA cycle under baseline conditions. Brief stimulation with 50 mM KCl causes a rapid decrease in DGC layer ATP, and a preferential increase in glucose metabolism relative to alternative fuel metabolism. Glucose preference occurs even under conditions of fuel com petition. This work achieves broad metabolite coverage from a spatially defined region of physiological tissue, in which metabolic states are rapidly preserve...
Source: Journal of Neurochemistry - November 6, 2023 Category: Neuroscience Authors: Elisa M. York,
Anne Miller,
Sylwia A. Stopka,
Juan Ram ón Martínez‐François,
Md Amin Hossain,
Gerard Baquer,
Michael S. Regan,
Nathalie Y. R. Agar,
Gary Yellen Tags: ORIGINAL ARTICLE Source Type: research
Sexual dimorphic distribution of G protein ‐coupled receptor 30 in pain‐related regions of the mouse brain
Sexually dimorphic distribution of G protein-coupled receptor 30 (GPR30) was found in six pain-related regions of the mouse brain. Sex-specific differences of neurons expressing GPR30 were found in the primary somatosensory cortex (S1), insular cortex (IC), lateral habenula (LHb), and nucleus tractus solitarius (NTS), and sexully dimorohic proportion of GPR30-positive neurons expressing CaMKII α were detected in basolateral complex of the amygdala (BLA) and medial preoptic nucleus (mPOA). Within the LHb, the expression of GPR30 varies with estrous cycle phase, and females in metestrus had few GPR30+ neurons than those in ...
Source: Journal of Neurochemistry - November 5, 2023 Category: Neuroscience Authors: You Li,
Zhenhua Jiang,
Wenqiang Zuo,
Chenchen Huang,
Jianshuai Zhao,
Peizheng Liu,
Jiajia Wang,
Jingzhi Guo,
Xiao Zhang,
Minghui Wang,
Yan Lu,
Wugang Hou,
Qun Wang Tags: ORIGINAL ARTICLE Source Type: research
Synaptotagmin ‐11 regulates immune functions of microglia in vivo
Membrane trafficking pathways play crucial roles in microglial immune responses. However, the molecular mechanisms underlying these processes remain largely elusive. Here, we reported that synaptotagmin-11 (Syt11), an abundant Syt isoform in the brain that is associated with Parkinson's disease and schizophrenia, regulated microglial migration, cytokine release, and phagocytosis in the mouse brain. Further investigation discovered that Syt11 inhibited cytokine release via direct interactions with vps10p-tail-interactor-1a (vti1a) and vti1b. Our study reveals a novel inhibitory mechanism of microglia-mediated inflammation, ...
Source: Journal of Neurochemistry - November 4, 2023 Category: Neuroscience Authors: Feifan Zhang,
Dong Yang,
Jingchen Li,
Cuilian Du,
Xinran Sun,
Wanru Li,
Fengwei Liu,
Yiwei Yang,
Yuhong Li,
Lei Fu,
Rena Li,
Claire Xi Zhang Tags: ORIGINAL ARTICLE Source Type: research
The ratio of M1 to M2 microglia in the striatum determines the severity of L ‐Dopa‐induced dyskinesias
We report that L-Dopa treatment leading to LIDs exacerbates activated microglia numbers beyond that associated with the PD state; the severity of LIDs is strongly correlated to the ratio of the striatal M1 to M2 microglial numbers; in non-dyskinetic mice, there is no M1/M2 microglia ra tio increase above that seen in PD mice; and reducing M1/M2 microglia ratio using anti-inflammatories is anti-dyskinetic. Parkinson's disease is associated with increased inflammation, but this is insufficient to underpin dyskinesia. Given that L-Dopa-treated non-LID mice show the same ratio of M1/M 2 microglia as PD mice that received no L-...
Source: Journal of Neurochemistry - November 3, 2023 Category: Neuroscience Authors: Peggy Rentsch,
Timothy Egan,
Andrea Kuriakose,
Sandy Stayte,
Bryce Vissel Tags: ORIGINAL ARTICLE Source Type: research
The effect of contact/collision sport participation without concussion on neurometabolites: A systematic review and meta ‐analysis of magnetic resonance spectroscopy studies
Our review examined neurometabolite levels assessed via magnetic resonance spectroscopy (MRS) in athletes undertaking contact/collision sport without concussion. Only studies employing proton (1H) MRS were found. In longitudinal studies (i.e. pre- vs. mid −/post- season), a reduction inN-acetylaspartate (NAA) and total creatine (tCr; creatine and phosphocreatine), but not glutamate –glutamine (Glx), myo-inositol (mI) or total choline (tCho; choline-containing compounds) was found. In case–control studies, contact/collision sport athletes had higher mI, but not NAA or tCr compared to non-contact sport athletes and non...
Source: Journal of Neurochemistry - November 1, 2023 Category: Neuroscience Authors: Nathan Delang,
Christopher Irwin,
Aimie L. Peek,
Iain S. McGregor,
Ben Desbrow,
Danielle McCartney Tags: SYSTEMATIC REVIEW Source Type: research
Circulating metabolites and risk of incident dementia: A prospective cohort study
Our results highlighted that the circulating levels of L-LDL-C% and L-LDL-CE% were associated with lower risk of all-cause dementia and AD, lower risk of cognitive deficits, and greater brain cortical and hippocampal brain volume, but not with VD. Circulating concentrations of S-HDL-CE were associated with lower risk of all-cause dementia and VD, but not with AD. These metabolites may play a role in the advancement of future intervention trials of dementia. AbstractIdentifying circulating metabolites associated with dementia, cognition, and brain volume may improve the understanding of dementia pathogenesis and provide nov...
Source: Journal of Neurochemistry - November 1, 2023 Category: Neuroscience Authors: Shu ‐Yi Huang,
Ya‐Ru Zhang,
Liu Yang,
Yu‐Zhu Li,
Bang‐Sheng Wu,
Shi‐Dong Chen,
Jian‐Feng Feng,
Qiang Dong,
Wei Cheng,
Jin‐Tai Yu Tags: ORIGINAL ARTICLE Source Type: research
Immunity impacts cognitive deficits across neurological disorders
Cognitive deficits are a common symptom of many neurodegenerative and neurological diseases such as multiple sclerosis, several dementias, mental health disorders, traumatic brain injury, and even normal aging. These disorders, despite their differences in etiology, feature prominent dysregulation of immune signaling molecules, including cytokines and chemokines. In this review, we highlight the association between several of these molecules with cognitive deficits observed in both patients and animal models, an understudied area of research. Understanding the immune dysregulation-associated commonalities between multiple ...
Source: Journal of Neurochemistry - October 30, 2023 Category: Neuroscience Authors: Benjamin C. Shaw,
Victoria R. Anders,
Rachel A. Tinkey,
Maria L. Habean,
Orion D. Brock,
Benjamin J. Frostino,
Jessica L. Williams Tags: REVIEW Source Type: research
Diet ‐induced diabetes is associated with lower hippocampal glycogen and reduced glycogenolysis following local exogenous insulin
In rats with high-fat diet-induced obesity and diabetes, hippocampal glycogen is reduced and is less responsive to acute intrahippocampal administration of insulin, which significantly reduces glycogen in the hippocampi of control animals: our data suggest that impaired fuel availability from glycogen may be a contributing factor to the cognitive impairment seen in disease states that include central insulin resistance, such as Alzheimer's disease. AbstractBrain fuel (specifically, glucose) supply and metabolism are well-established to be limiting factors for cognitive performance, with the largest body of data being for h...
Source: Journal of Neurochemistry - October 27, 2023 Category: Neuroscience Authors: Ewan C. McNay Tags: ORIGINAL ARTICLE Source Type: research
