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2. Letters

Author

Patricios, N. N., Hester, Marcus, Duncan, Elmer H., Molnar, François, Coler, Myron A., Gibson, James J., Rothschild, Lincoln, Marcheschi, Louis R., Keel, John S., Harrison, Lee, and Goldman, James A.

Published
2017

3. Multi-omic analysis of Huntington’s disease reveals a compensatory astrocyte state

Author

Paryani, Fahad, Kwon, Ji-Sun, Ng, Christopher W., Jakubiak, Kelly, Madden, Nacoya, Ofori, Kenneth, Tang, Alice, Lu, Hong, Xia, Shengnan, Li, Juncheng, Mahajan, Aayushi, Davidson, Shawn M., Basile, Anna O., McHugh, Caitlin, Vonsattel, Jean Paul, Hickman, Richard, Zody, Michael C., Housman, David E., Goldman, James E., Yoo, Andrew S., Menon, Vilas, and Al-Dalahmah, Osama

Published
2024
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4. Letters

Author

M’Bow, Amadou-Mahtar, Topper, David R., Goler, Robert I., Olson, Lynn, Zajec, Edward, Morgan, Robert C., Fisher, John, Goldman, James A., Hurwitz, Al, Emmer, Michele, Rauschenbach, Boris V., Wells, Alan, Goodman, Nelson, and Viora, Jean-Louis

Published
2017

29. Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy

Author

Miller, Katherine E., Rivaldi, Adithe C., Shinagawa, Noriyuki, Sran, Sahib, Navarro, Jason B., Westfall, Jesse J., Miller, Anthony R., Roberts, Ryan D., Akkari, Yassmine, Supinger, Rachel, Hester, Mark E., Marhabaie, Mohammad, Gade, Meethila, Lu, Jinfeng, Rodziyevska, Olga, Bhattacharjee, Meenakshi B., Von Allmen, Gretchen K., Yang, Edward, Lidov, Hart G. W., Harini, Chellamani, Shah, Manish N., Leonard, Jeffrey, Pindrik, Jonathan, Shaikhouni, Ammar, Goldman, James E., Pierson, Christopher R., Thomas, Diana L., Boué, Daniel R., Ostendorf, Adam P., Mardis, Elaine R., Poduri, Annapurna, Koboldt, Daniel C., Heinzen, Erin L., and Bedrosian, Tracy A.

Published
2023
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30. Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia

Author

Zazhytska, Marianna, Kodra, Albana, Hoagland, Daisy A, Frere, Justin, Fullard, John F, Shayya, Hani, McArthur, Natalie G, Moeller, Rasmus, Uhl, Skyler, Omer, Arina D, Gottesman, Max E, Firestein, Stuart, Gong, Qizhi, Canoll, Peter D, Goldman, James E, Roussos, Panos, tenOever, Benjamin R, Overdevest, Jonathan B, and Lomvardas, Stavros

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Neurosciences, Infectious Diseases, Genetics, Prevention, Lung, Biodefense, Vaccine Related, Emerging Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Animals, Anosmia, COVID-19, Cricetinae, Down-Regulation, Humans, Receptors, Odorant, SARS-CoV-2, Smell, anosmia, nuclear architecture, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage in a variety of organs. Thus, deciphering the non-cell-autonomous effects of SARS-CoV-2 infection is imperative for understanding the cellular and molecular disruption it elicits. Neurological and cognitive defects are among the least understood symptoms of COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both in humans and hamsters, SARS-CoV-2 infection causes widespread downregulation of olfactory receptors (ORs) and of their signaling components. This non-cell-autonomous effect is preceded by a dramatic reorganization of the neuronal nuclear architecture, which results in dissipation of genomic compartments harboring OR genes. Our data provide a potential mechanism by which SARS-CoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect, offering insight to its systemic effects in olfaction and beyond.

Published
2022

32. Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

Author

Lim, Ryan G, Al-Dalahmah, Osama, Wu, Jie, Gold, Maxwell P, Reidling, Jack C, Tang, Guomei, Adam, Miriam, Dansu, David K, Park, Hye-Jin, Casaccia, Patrizia, Miramontes, Ricardo, Reyes-Ortiz, Andrea M, Lau, Alice, Hickman, Richard A, Khan, Fatima, Paryani, Fahad, Tang, Alice, Ofori, Kenneth, Miyoshi, Emily, Michael, Neethu, McClure, Nicolette, Flowers, Xena E, Vonsattel, Jean Paul, Davidson, Shawn, Menon, Vilas, Swarup, Vivek, Fraenkel, Ernest, Goldman, James E, and Thompson, Leslie M

Subjects
Biological Sciences, Genetics, Brain Disorders, Neurodegenerative, Neurosciences, Huntington's Disease, Human Genome, Rare Diseases, Nutrition, 2.1 Biological and endogenous factors, Neurological, Animals, Humans, Mice, Biotin, Dietary Supplements, Disease Models, Animal, Huntington Disease, Mice, Transgenic, Nerve Tissue Proteins, Oligodendroglia, Solitary Nucleus, Thiamine
Abstract

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Published
2022

33. Metabolic Enzyme Alterations and Astrocyte Dysfunction in a Murine Model of Alexander Disease With Severe Reactive Gliosis

Author

Heaven, Michael R, Herren, Anthony W, Flint, Daniel L, Pacheco, Natasha L, Li, Jiangtao, Tang, Alice, Khan, Fatima, Goldman, James E, Phinney, Brett S, and Olsen, Michelle L

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Neurosciences, Neurodegenerative, Genetics, Rare Diseases, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Alexander Disease, Animals, Astrocytes, Disease Models, Animal, Gliosis, Humans, Mice, Mice, Transgenic, Mutation, Proteomics, Alexander disease, Fabp7, Ugt8, astrocytes, reactive gliosis, Biochemistry & Molecular Biology
Abstract

Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice.

Published
2022

34. Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

Author

Al-Dalahmah, Osama, Lam, Matti, McInvale, Julie J., Qu, Wenhui, Nguyen, Trang, Mun, Jeong-Yeon, Kwon, Sam, Ifediora, Nkechime, Mahajan, Aayushi, Humala, Nelson, Winters, Tristan, Angeles, Ellen, Jakubiak, Kelly A., Kühn, Rebekka, Kim, Yoon A., De Rosa, Maria Caterina, Doege, Claudia A., Paryani, Fahad, Flowers, Xena, Dovas, Athanassios, Mela, Angeliki, Lu, Hong, DeTure, Michael A., Vonsattel, Jean Paul, Wszolek, Zbigniew K., Dickson, Dennis W., Kuhlmann, Tanja, Zaehres, Holm, Schöler, Hans R., Sproul, Andrew A., Siegelin, Markus D., De Jager, Philip L., Goldman, James E., Menon, Vilas, Canoll, Peter, and Hargus, Gunnar

Published
2024
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35. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Warner, Thomas T, Jaunmuktane, Zane, Boeve, Bradley F, Duara, Ranjan, Graff-Radford, Neill R, Josephs, Keith A, Knopman, David S, Koga, Shunsuke, Murray, Melissa E, Lyons, Kelly E, Pahwa, Rajesh, Petersen, Ronald C, Whitwell, Jennifer L, Grinberg, Lea T, Miller, Bruce, Schlereth, Athena, Spina, Salvatore, Grossman, Murray, Irwin, David J, Suh, EunRan, Trojanowski, John Q, Van Deerlin, Vivianna M, Wolk, David A, Connors, Theresa R, Dooley, Patrick M, Oakley, Derek H, Aldecoa, Iban, Balasa, Mircea, Gelpi, Ellen, Borrego-Écija, Sergi, Gascon-Bayarri, Jordi, Sánchez-Valle, Raquel, Sanz-Cartagena, Pilar, Piñol-Ripoll, Gerard, Bigio, Eileen H, Flanagan, Margaret E, Rogalski, Emily J, Weintraub, Sandra, Schneider, Julie A, Peng, Lihua, Zhu, Xiongwei, Chang, Koping, Troncoso, Juan C, Prokop, Stefan, Newell, Kathy L, Jones, Matthew, Richardson, Anna, Roncaroli, Federico, Snowden, Julie, Allinson, Kieren, Singh, Poonam, Serrano, Geidy E, Flowers, Xena E, Goldman, James E, Heaps, Allison C, Leskinen, Sandra P, Black, Sandra E, Masellis, Mario, King, Andrew, Al-Sarraj, Safa, Troakes, Claire, Hodges, John R, Kril, Jillian J, Kwok, John B, Piguet, Olivier, Roeber, Sigrun, Attems, Johannes, Thomas, Alan J, Evers, Bret M., Bieniek, Kevin F, Sieben, Anne A, Cras, Patrick P, De Vil, Bart B, Bird, Thomas, Castellani, Rudolph J, Chaffee, Ann, Franklin, Erin, Haroutunian, Vahram, Jacobsen, Max, Keene, Dirk, Latimer, Caitlin S, Metcalf, Jeff, Perrin, Richard J, Purohit, Dushyant P, Rissman, Robert A, Schantz, Aimee, Walker, Jamie, De Deyn, Peter P, Duyckaerts, Charles, Le Ber, Isabelle, Seilhean, Danielle, Turbant-Leclere, Sabrina, Ervin, John F, Nennesmo, Inger, Riehl, James, Nacmias, Benedetta, Finger, Elizabeth C, Blauwendraat, Cornelis, Nalls, Mike A, Singleton, Andrew B, Vitale, Dan, Cunha, Cristina, Wszolek, Zbigniew K, Valentino, Rebecca R, Scotton, William J, Roemer, Shanu F, Lashley, Tammaryn, Heckman, Michael G, Shoai, Maryam, Martinez-Carrasco, Alejandro, Tamvaka, Nicole, Walton, Ronald L, Baker, Matthew C, Macpherson, Hannah L, Real, Raquel, Soto-Beasley, Alexandra I, Mok, Kin, Revesz, Tamas, Christopher, Elizabeth A, DeTure, Michael, Seeley, William W, Lee, Edward B, Frosch, Matthew P, Molina-Porcel, Laura, Gefen, Tamar, Redding-Ochoa, Javier, Ghetti, Bernardino, Robinson, Andrew C, Kobylecki, Christopher, Rowe, James B, Beach, Thomas G, Teich, Andrew F, Keith, Julia L, Bodi, Istvan, Halliday, Glenda M, Gearing, Marla, Arzberger, Thomas, Morris, Christopher M, White, Charles L, 3rd, Mechawar, Naguib, Boluda, Susana, MacKenzie, Ian R, McLean, Catriona, Cykowski, Matthew D, Wang, Shih-Hsiu J, Graff, Caroline, Nagra, Rashed M, Kovacs, Gabor G, Giaccone, Giorgio, Neumann, Manuela, Ang, Lee-Cyn, Carvalho, Agostinho, Morris, Huw R, Rademakers, Rosa, Hardy, John A, Dickson, Dennis W, Rohrer, Jonathan D, and Ross, Owen A

Published
2024
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36. Reactive astrocyte nomenclature, definitions, and future directions

Author

Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P, Petzold, Gabor C, Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J, Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E, Bonvento, Gilles, Butt, Arthur M, Chen, Wei-Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E, Goldman, Steven A, Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G, Heiland, Dieter H, Hol, Elly M, Holt, Matthew G, Iino, Masamitsu, Kastanenka, Ksenia V, Kettenmann, Helmut, Khakh, Baljit S, Koizumi, Schuichi, Lee, C Justin, Liddelow, Shane A, MacVicar, Brian A, Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V, Murai, Keith K, Norris, Christopher M, Okada, Seiji, Oliet, Stéphane HR, Oliveira, João F, Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G, Pfrieger, Frank W, Poskanzer, Kira E, Quintana, Francisco J, Ransohoff, Richard M, Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R, Rothstein, Jeffrey D, Rouach, Nathalie, Rowitch, David H, Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A, Vitorica, Javier, Wanner, Ina-Beate, Wood, Levi B, Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R, Zorec, Robert, Sofroniew, Michael V, and Verkhratsky, Alexei

Subjects
Neurosciences, Brain Disorders, Neurological, Aging, Animals, Astrocytes, Brain, Brain Diseases, Brain Injuries, Humans, Spinal Cord, Spinal Cord Injuries, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

Published
2021

44. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Valentino, Rebecca R, primary, Scotton, William J, additional, Roemer, Shanu F, additional, Lashley, Tammaryn, additional, Heckman, Michael G, additional, Shoai, Maryam, additional, Martinez-Carrasco, Alejandro, additional, Tamvaka, Nicole, additional, Walton, Ronald L, additional, Baker, Matthew C, additional, Macpherson, Hannah L, additional, Real, Raquel, additional, Soto-Beasley, Alexandra I, additional, Mok, Kin, additional, Revesz, Tamas, additional, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Seeley, William W, additional, Lee, Edward B, additional, Frosch, Matthew P, additional, Molina-Porcel, Laura, additional, Gefen, Tamar, additional, Redding-Ochoa, Javier, additional, Ghetti, Bernardino, additional, Robinson, Andrew C, additional, Kobylecki, Christopher, additional, Rowe, James B, additional, Beach, Thomas G, additional, Teich, Andrew F, additional, Keith, Julia L, additional, Bodi, Istvan, additional, Halliday, Glenda M, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Morris, Christopher M, additional, White, Charles L, additional, Mechawar, Naguib, additional, Boluda, Susana, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nagra, Rashed M, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Carvalho, Agostinho, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, Ross, Owen A, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, additional, Duara, Ranjan, additional, Graff-Radford, Neill R, additional, Josephs, Keith A, additional, Knopman, David S, additional, Koga, Shunsuke, additional, Murray, Melissa E, additional, Lyons, Kelly E, additional, Pahwa, Rajesh, additional, Petersen, Ronald C, additional, Whitwell, Jennifer L, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, additional, Suh, EunRan, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Wolk, David A, additional, Connors, Theresa R, additional, Dooley, Patrick M, additional, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Schneider, Julie A, additional, Peng, Lihua, additional, Zhu, Xiongwei, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Jones, Matthew, additional, Richardson, Anna, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Singh, Poonam, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Black, Sandra E, additional, Masellis, Mario, additional, King, Andrew, additional, Al-Sarraj, Safa, additional, Troakes, Claire, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Thomas, Alan J, additional, Evers, Bret M., additional, Bieniek, Kevin F, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, Bird, Thomas, additional, Castellani, Rudolph J, additional, Chaffee, Ann, additional, Franklin, Erin, additional, Haroutunian, Vahram, additional, Jacobsen, Max, additional, Keene, Dirk, additional, Latimer, Caitlin S, additional, Metcalf, Jeff, additional, Perrin, Richard J, additional, Purohit, Dushyant P, additional, Rissman, Robert A, additional, Schantz, Aimee, additional, Walker, Jamie, additional, De Deyn, Peter P, additional, Duyckaerts, Charles, additional, Le Ber, Isabelle, additional, Seilhean, Danielle, additional, Turbant-Leclere, Sabrina, additional, Ervin, John F, additional, Nennesmo, Inger, additional, Riehl, James, additional, Nacmias, Benedetta, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, and Wszolek, Zbigniew K, additional

Published
2024
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45. Cyclophilin D-dependent oligodendrocyte mitochondrial ion leak contributes to neonatal white matter injury

Author

Niatsetskaya, Zoya, Sosunov, Sergey, Stepanova, Anna, Goldman, James, Galkin, Alexander, Neginskaya, Maria, Pavlov, Evgeny, and Ten, Vadim

Subjects
Premature infants
Abstract

Introduction In the United States, each year approximately 60,000 infants are delivered prematurely with very low birth weight (VLBW) of less than 1500 g (1). In VLBW infants, white matter [...], Postnatal failure of oligodendrocyte maturation has been proposed as a cellular mechanism of diffuse white matter injury (WMI) in premature infants. However, the molecular mechanisms for oligodendrocyte maturational failure remain unclear. In neonatal mice and cultured differentiating oligodendrocytes, sublethal intermittent hypoxic (IH) stress activated cyclophilin D-dependent mitochondrial proton leak and uncoupled mitochondrial respiration, leading to transient bioenergetic stress. This was associated with development of diffuse WMI: poor oligodendrocyte maturation, diffuse axonal hypomyelination, and permanent sensorimotor deficit. In normoxic mice and oligodendrocytes, exposure to a mitochondrial uncoupler recapitulated the phenotype of WMI, supporting the detrimental role of mitochondrial uncoupling in the pathogenesis of WMI. Compared with WT mice, cyclophilin D-knockout littermates did not develop bioenergetic stress in response to IH challenge and fully preserved oligodendrocyte maturation, axonal myelination, and neurofunction. Our study identified the cyclophilin D-dependent mitochondrial proton leak and uncoupling as a potentially novel subcellular mechanism for the maturational failure of oligodendrocytes and offers a potential therapeutic target for prevention of diffuse WMI in premature infants experiencing chronic IH stress.

Published
2020
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48. The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra

Author

Jakubiak, Kelly, primary, Paryani, Fahad, additional, Kannan, Adithya, additional, Lee, Jaeseung, additional, Madden, Nacoya, additional, Li, Juncheng, additional, Chen, David, additional, Mahajan, Aayushi, additional, Xia, Shengnan, additional, Flowers, Xena, additional, Menon, Vilas, additional, Sulzer, David, additional, Goldman, James, additional, Sims, Peter A., additional, and Al-Dalahmah, Osama, additional

Published
2024
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