Proyectos activos como investigador principal
1. APP-35358 (Morales)
USDA/APHIS
Dates: 09/30/2023 – 09/29/2024
Role: Principal Investigator
Identification and characterization of CWD contaminated meats.
This study will measure the CWD prion infectivity titers in contaminated meats using in vitro and in vivo assays. In this project, we will also develop new screening techniques for these products.
2. APP-35369 (Morales)
USDA/APHIS
Dates: 09/30/2023 – 09/29/2024
Role: Principal Investigator
Feral swine as spreaders of Chronic Wasting Disease prions.
Here, we will identify the presence of prions in feces and intestinal tissues from wild hogs living in CWD endemic areas using prion replication assays.
3. Just Missed Funds (Morales)
McGovern Medical School – UTHealth
Dates: 06/01/2023 – 11/30/2023
Role: Principal Investigator
Aβ seeding activity in eyes from AD patients.
This pilot project will preliminarily analyze the seeding activity of disease-associated Aβ in the eyes of AD patients using in vitro and in vivo assays.
4. APP-20115 (Morales)
USDA/APHIS
Dates: 10/01/2022 – 09/30/2023
Role: Principal Investigator
Exploring new uses for PMCA and RT-QuIC diagnosis: prion strain discrimination and soil contamination.
This project will characterize different CWD prion strains recently identified in Texas, and standardize prion diagnostic methods to screen different soil types found in Texas.
5. AARGD-22-972125 (Morales)
Alzheimer’s Association
Dates: 01/01/2023 – 12/31/2025
Role: Principal Investigator
Cross-seeding between bacterial and mammalian amyloids.
This study will explore whether specific bacterial components (bacterial amyloids) accelerate AD/PD phenotypes by “cross-seeding” the misfolding of Aβ, tau, or α-synuclein.
6. G21AC10486 (Morales)
United States Geological Survey (USGS)
Dates: 09/01/2022 – 08/31/2024
Role: Principal Investigator
Going up in smoke: assessing the ability of incineration to inactivate CWD prions from carcasses.
The main goal of this study is to quantify prion titers in tissues derived from CWD-infected white-tailed deer. These characterized samples will then made available to the scientific community for standardization purposes. This is a subcontract from a larger project provided to the University of Wisconsin-Madison.
7. AGT009122 (Morales/Barichello, MPI)
Texas Alzheimer’s Research and Care Consortium (TARCC)
Dates: 09/01/2022 – 08/31/2024
Role: Principal Investigator
Effect of COVID-19 in AD, PD and associated protein misfolding.
Here, we will measure biomarkers of AD and PD in longitudinally collected blood plasma samples from COVID-19 patients. Results will be confronted with inflammatory profiles and psychiatric statuses.
8. CJDF2022/2024 (Morales)
Creutzfeldt-Jakob Disease Foundation
Dates: 03/01/2022 – 02/28/2024
Role: Principal Investigator
Development of a high throughput system for screening anti-prion molecules.
The objective of this proposal is to develop an in vitro high throughput screening system to identify strain-specific anti-prion molecules.
9. 22-7100-0453-CA UTH (Morales)
USDA/APHIS
Dates: 10/15/2021 – 10/14/2023
Role: Principal Investigator
In vitro and in vivo evaluation of CWD prions in feral swine.
The goal of this project is to identify the presence of infectious prions in biological samples derived from wild feral swine using PMCA and bioassays.
10. R01AI132695-05S1 (Morales)
NIH/NIAID/NIA
Dates: 06/08/2021 – 05/31/2023 (NCE)
Role: Principal Investigator
Shedding, retention and spreading of chronic wasting disease prions in the environment (supplement).
In this project, we will assess the potential of surgical materials exposed to disease-associated Aβ and tau proteins to propagate protein misfolding.
11. RF1AG072491 (Morales/Barichello, MPI)
NIH/NIA
Dates: 05/15/2021 – 04/30/2024
Role: Principal Investigator
Infection-driven mechanisms associated with Alzheimer’s disease pathology
In this project we will evaluate whether peripheral infection mediated by sepsis and brain infection induced by meningitis represent a causal component of AD.
12. RF1AG059321 (Soto/Morales, MPI)
NIH/NIA
Dates: 09/01/2020 – 08/31/2024
Role: Principal Investigator
Role of circulating Abeta seeds and peripheral tissue damage in Alzheimer’s disease pathogenesis.
The experiments listed in this proposal will help to elucidate the contribution of circulating amyloid-beta aggregates in Alzheimer’s disease (AD) pathogenesis. Specifically, we will explore whether decreased amyloid-beta clearance due to liver damage represent a risk factor for AD dementia.
13. 1R01AI132695-03S1 (Morales)
NIH/NIAID
Dates: 08/25/2019 – 05/31/2023 (NCE)
Role: Principal Investigator
Shedding, retention and spreading of chronic wasting disease prions in the environment (supplement).
This project will focus in assessing whether chronic wasting disease and scrapie prions can induce the misfolding of proteins involved in Alzheimer’s disease (Aβ and tau). This will be done using in vitro systems and transgenic mice.
14. R01AI132695 (Morales)
NIH/NIAID
Dates: 06/01/2017 – 05/31/2023 (NCE)
Role: Principal Investigator
Shedding, retention and spreading of chronic wasting disease prions in the environment.
This project will explore the contamination dynamics of Chronic Wasting Disease in the environment, focusing specifically in natural and manmade components as vectors for disease transmission.
- Refereed Original Articles in Journals
- Pastrana, M.A.; Sajnani, G; Onisko, B.; Castilla, J.; Morales, R.; Soto, C.; Requena, J. R. “Isolation and characterization of a proteinase K sensitive PrPSc fraction”. Biochemistry. 2006; 45 (51): 15710-15717
- Castilla, J.; Gonzalez-Romero, D.; Saa, P.; Morales, R.; De Castro, J. and Soto C. “Crossing the species barrier by PrPSc replication in vitro generates unique infectious prions”. Cell. 2008; 134 (5): 757-768.
- Gonzalez-Romero, D.; Barria, M.; Leon, P. Morales, R. and Soto, C. “Detection of infectious prions in urine”. FEBS Lett. 2008; 582 (21-22): 3161-3166.
- Castilla, J.*; Morales, R.*; Saa, P.; Barria, M.; Gambetti, P. and Soto, C. “Cell-free propagation of prion strains”. EMBO Journal. 2008; 27: 2557-2566. (*These authors contributed equally to this work)
- Morales, R.; Buytaert-Hoefen, K.; Gonzalez-Romero, D.; Castilla, J.; Hansen, E.; Hlavinka, D.; Goodrich, R. and Soto, C. “Reduction of prion infectivity in packed red blood cells”. Biochemical and Biophysical Research Communications. 2008; 377 (2): 373-378.
- Piro, J.R.; Harris, B.T.; Nishina, K.; Soto, C.; Morales, R.; Rees, J.R. and Supattapone, S. “Prion protein glycosylation is not required for strain-specific neurotropism”. Journal of Virology. 2009; 83 (11): 5321-5328
- Barria, M.A.; Mukherjee, A.; Gonzalez-Romero, D.; Morales, R. and Soto, C. “De novo generation of infectious prions in vitro produces a new disease phenotype”. PLoS Pathogens. 2009; 5 (5): e1000421
- Morales, R.; Estrada, L.D.; Diaz-Espinoza, R.; Morales-Scheihing, D.; Jara, M.C.; Castilla, J. and Soto, C. “Molecular cross talk between misfolded proteins in animal models of Alzheimer’s and prion diseases”. The Journal of Neuroscience. 2010; 301 (13): 4528-4535.
- Abid, K. Morales, R. and Soto, C. “Cellular factors implicated in prion replication.” FEBS Letters. 2010; 584 (11) :2409-2414
- Chen, B.; Morales, R.; Barria, M.A. and Soto, C. “Estimating prion concentration in fluids and tissues by quantitative PMCA.” Nature Methods. 2010; 7 (7): 519-520.
- Urayama, A.; Morales, R.; Niehoff, M.L.; Banks W.A. and Soto, C. “Initial Fate of Prions upon Peripheral Infection: Half-life, Distribution, Clearance and Tissue Uptake”. FASEB J. 2011; 25(8): 2792-2803
- Morales, R.; Duran-Aniotz, C.A.; Castilla, J.; Estrada, L.D. and Soto, C. “De Novo Induction of amyloid-β Deposition in vivo”. Molecular Psychiatry. 2012; 17: 1347–1353
- Morales, R.; Duran-Aniotz, C.A.; Diaz-Espinoza, R.; Camacho, M. and Soto, C. “Protein Misfolding Cyclic Amplification (PMCA) of Infectious Prions”. Nature Protocols. 2012; 7 (7): 1397-1409.
- Duran-Aniotz, C.A.; Moreno-Gonzalez, I. and Morales, R. “Agregados Amiloides: Rol en Desórdenes de Conformación Proteica” (“Amyloid Aggregates: Role in Protein Misfolding Disorders”). Revista Médica de Chile. 2013; 141, 494-504. (Article in Spanish).
- Morales, R.; Pritzkow, S.; Hu, P.P.; Duran-Aniotz, C. and Soto, C. “Lack of prion transmission by sexual or parental routes in experimentally infected hamsters”. Prion. 2013; 7 (5). 4161/pri.26747
- Duran-Aniotz, C.; Morales, R.; Moreno-Gonzalez, I.; Hu, P.P. and Soto, C. “Brains from Non-Alzheimer’s individuals containing amyloid deposits accelerate Aβ deposition in vivo”. Acta Neuropathologica Communications. 2013; 1:76.
- Chen, B.; Soto, C. and Morales, R. “Peripherally administrated prions reach the brain at sub-infectious quantities in experimental hamsters”. FEBS Letters. 2014; 588, 795-800.
- Duran-Aniotz, C.; Morales, R.; Moreno-Gonzalez, I.; Hu, P.P.; Fedynyshyn, J. and Soto, C. “Aggregate-depleted brain fails to induce Aβ deposition in a mouse model of Alzheimer’s disease”. PLoS One. 2014; 9(2): e89014.
- Morales, R.*; Bravo-Alegria, J.*; Duran-Aniotz, C.; and Soto, C. “Titration of biologically active amyloid–β seeds in a transgenic mouse model of Alzheimer’s disease”. Scientific Reports. 2015; 5: 9349. (*These authors contributed equally to this work).
- Pritzkow, S.; Morales, R.; Moda, F.; Khan, U.; Telling, G.; Hoover, E. and Soto, C. “Grass plants bind, retain, uptake and transport infectious prions”. Cell Reports. 2015; http:// dx.doi.org/10.1016/j.celrep.2015.04.036.
- Morales, R.*,¥; Hu, P. P.*; Duran-Aniotz, C.; Moda, F.; Diaz-Espinoza, R.; Chen, B.; Bravo-Alegria, J.; Makarava, N.; Baskakov, I. V. and Soto, C¥. “Strain-dependent profile of misfolded prion protein aggregates”. Scientific Reports. 6, 20526. (*These authors contributed equally to this work. ¥Corresponding authors).
- Hu, P. P.; Morales, R.; Duran-Aniotz, C.; Moreno-Gonzalez, I.; Khan, U. and Soto, C. “Role of prion replication in the strain-dependent brain regional distribution of prions”. Journal of Biological Chemistry. 2016; 291, 12880-12887.
- Park, K-W.; Kim, G. E.; Morales, R.; Moda, F.; Moreno-Gonzalez, I.; Concha-Marambio, L.; Lee, A. S.; Hetz, C. and Soto, C. “The endoplasmic reticulum chaperone GRP78/BiP modulates prion propagation in vitro and in vivo”. Scientific Reports. 2017; 7, 44723.
- Kramm, C.; Pritzkow, S.; Lyon, A.; Nichols, T. Morales, R.* and Soto, C.*. “Detection of prions in blood of cervids at the asymptomatic stage of chronic wasting disease”. Scientific Reports. 2017; 7:17241. (*Corresponding authors).
- Diaz-Espinoza, R.; Morales, R.; Concha-Marambio, L.; Moreno-Gonzalez, I.; Moda, F. and Soto, C. “Treatment with a non-toxic, self-replicating anti-prion delays or prevents prion disease in vivo”. Molecular Psychiatry. 2018; 23 (3), 777-788.
- Pritzkow, S.; Morales, R.; Lyon, A.; Concha-Marambio, L.; Urayama, A. and Soto, C. “Efficient prion disease transmission through environmental materials”. Journal of Biological Chemistry. 2018; 293 (9), 3363-3373.
- Mays, C.; Armijo, E.; Morales, R.; Kramm, C.; Flores, A.; Tiwari, A.; Bian, J.; Telling, G.C.; Pandita, T.K.; Hunt, C.R. and Soto, C. “Prion disease is accelerated in mice devoid of stress-induced heat shock protein 70 (HSP70)”. Journal of Biological Chemistry. 2019; 294 (37): 13619-13628.
- Edwards, G.; Gamez, N.; Armijo, E.; Kramm, C.; Morales, R.; Taylor-Presse, K.; Schulz, P.; Soto, C. and Moreno-Gonzalez, I. “Peripheral delivery of neural precursors cells ameliorates Parkinson’s disease-associated pathology”. Cells. 2019; 8 (11), 1359; https://doi.org/10.3390/cells8111359.
- Kramm, C.; Gomez-Gutierrez, R.; Soto, C.; Telling, G.; Nichols, T. A. and Morales, R. “In vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white-tailed deer bucks (Odocoileus virginianus)”. PLoS One. 2019; 14 (12): e0226560.
- Gomez, W.; Morales, R.; Maracaja-Coutinho, V.; Parra, V. and Nassif, M. “Down syndrome and Alzheimer’s disease: common molecular traits beyond the amyloid precursor protein”. Aging. 2020; 12 (1): 1011-1033.
- Huang, Y.; Ma, J.; Morales, R.; and Tang, H. “Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N- homozygous 129M genotype”. Prion. 2020; 14 (1): 232-237.
- Kramm, C.; Soto, P.; Nichols, T.A. and Morales, R. “Chronic wasting disease (CWD) prion detection in blood from pre-symptomatic white-tailed deer harboring PRNP polymorphic variants”. Scientific Reports. 2020; 10, 19763.
- Morales, R.*, ¥; Duran-Aniotz, C.*; Bravo-Alegria, J.; Estrada, L. D.; Shahnawaz, M.; Hu, P.P.; Kramm, C.; Morales-Scheihing, D.; Urayama, A. and Soto, C¥. “Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease”. Acta Neuropathologica Communications. 2020; 8: 213. (*These authors contributed equally to this work. ¥Corresponding authors).
- Duran-Aniotz, C.; Moreno-Gonzalez, I; Gamez, N; Perez-Urrutia, N.; Vegas-Gomez, L.; Soto, C. and Morales, R. “Amyloid pathology arrangements in Alzheimer’s disease brains modulate in vivo seeding capability”. Acta Neuropathologica Communications. 2021; 9:56.
- Morales, R.*, ¥; Bravo-Alegria, J.*; Moreno-Gonzalez, I.; Duran-Aniotz, C.; Gamez, N.; Edwards, G. and Soto, C¥. “Transmission of cerebral amyloid pathology by peripheral administration of misfolded Aβ aggregates”. Molecular Psychiatry. 2021; 26:5690-5701. (*These authors contributed equally to this work. ¥Corresponding authors).
- Huang, Y.; Wang, P.; Morales, R.; Luo, Q. and Ma, J. “Map2k5 deficient mice manifest phenotypes and pathological changes of dopamine deficiency in the central nervous system”. Frontiers in Aging Neuroscience. 2021. 13:651638. doi: 10.3389/fnagi.2021.651638.
- Kim, E.; Nohara, K.; Wirianto, M.; Escobedo, G.; Lim, J.Y.; Morales, R.; Yoo, S-H. and Chen, Z. “Effects of the clock modulator nobiletin on circadian rhythms and pathophysiology in female mice of an Alzheimer’s disease model”. 2021. 11, 1004. doi.org/10.3390/biom11071004.
- Bravo-Risi, F.; Soto, P.; Eckland, T.; Dittmar, R.; Ramirez, S.; Catumbela, C.S.G.; Soto, C.; Lockwood, M.; Nichols, T. and Morales, R. “Detection of CWD prions in naturally infected white-tailed deer fetuses and gestational tissues by PMCA”. Scientific Reports. 2021. 11:18385.
- Pritzkow, S.; Morales, R.; Camacho, M. and Soto, C. “Earthworms as carriers of infectious prions”. Emerging Infectious Diseases. 2021; 27(12): 3151-3154.
- Loureiro, J.A.; Andrade, S.; Goderis, L.; Gomez-Gutierrez, R.; Soto, C.; Morales, R.; and Pereira, M.C. “(De)stabilization of alpha-synuclein fibrillary aggregation by charged and uncharged surfactants”. International Journal of Molecular Sciences. 2021; 22:12509.
- Dandekar, M.P.; Yin, X.; Peng, T.; Devaraj, S.; Morales, R.; McPherson, D.D. and Huang, S-L. “Repetitive Xenon treatment improves post-stroke sensorimotor and neuropsychiatric dysfunction”. Journal of Affective Disorders. 2022; 301: 315-330.
- Moreno-Gonzalez, I.; Edwards III, G.; Morales, R.; Duran-Aniotz, C.; Escobedo, G.; Marquez, M.; Pumarola, M. and Soto, C. “Aged cattle brain displays Alzheimer’s disease-like pathology and promotes brain amyloidosis in transgenic animal model”. Frontiers in Aging Neuroscience. 2022; 13:815361.
- Wirianto, M.; Wang, C-Y; Kim, E.; Koike, N.; Gomez-Gutierrez, R.; Nohara, K.; Escobedo, G.; Choi, J.M.; Han, C.; Yagita, K.; Jung, S.J.; Soto, C.; Lee, H.K.; Morales, R.; Yoo, S-H. and Chen, Z. “The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Alzheimer’s disease model”. FASEB Journal. 2022; 36(3):e22186.
- Mudimela, S.; Vishwanath, N. K.; Pillai, A.; Morales, R.; Marelli, S. P.; Barichello, T. and Giridharan, V. V. “Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders – state of the art review”. Drug Discovery Today. 2022; 27(11):103334.
- Andrade, S.; Loureiro, J.A.; Ramirez, S.; Catumbela, C.; Soto, C.; Morales, R.*; do Carmo Pereira, M.* “Multi-dose intravenous administration of neutral and cationic liposomes in mice: an extensive toxicity study”. Pharmaceuticals. 2022; 15(6): 761. (*Corresponding authors).
- Gamez, N.; Bravo-Alegria, J; Huang, Y.; Perez-Urrutia, N.; Dongarwar, D.; Soto, C.; Morales, R. “Altering brain amyloidosis by intra-lingual and extra-nasal exposure of Aβ aggregates”. Cells. 2022; 11(21):3442.
- Azevedo Cardoso, T.; Silva, R. H.; Fernandes, J. L.; Arent, C. O.; Amboni, G.; Borba, L. A.; Padilha A. P. Z.; Botelho, M. E. M.; Maciel, A. L.; Barichello, T.; Morales, R.; Soares, S. J. B.; Bagatini, M. D.; Dallagnol, C.; Brighentini, M. E.; Ignacio, Z. M.; Quevedo, J.; Ceretta, L. B. and Zilli-Reus, G. “Stress levels, psychological symptoms, and C-reactive protein levels in COVID-19: a cross-sectional study”. Journal of Affective Disorders. 2023; 330:216-226.
- Inzalaco, H. N.; Bravo-Risi, F.; Morales, R.; Walsh, D. P.; Storm, D. J.; Pedersen, J. A.; Turner, W. C. and Lichtenberg, S. S. “Ticks harbor and excrete chronic wasting disease prions”. Scientific Reports. 2023. Accepted.
- Gomez-Gutierrez, R.; Ghosh, U.; Yau, W-M.; Gamez, N.; Do, K.; Kramm, C.; Shirani, H. Vegas-Gomez, L.; Schulz, J.; Moreno-Gonzalez, I.; Gutierrez, A.; Nilsson, P. R.; Tycko, R.; Soto, C. and Morales, R. “Two structurally defined Aβ polymorphs promote different pathological changes in susceptible mice”. EMBO Reports. 2023. Accepted.
- Catumbela, C. S. G.; Giridharan, V. V.; Barichello, T. and Morales, R. “Clinical Evidence of Human Pathogens Implicated in AD Pathology and the Therapeutic Efficacy of Antimicrobials: An Overview”. Translational Neurodegeneration. 2023. Accepted.
- V.; Catumbela, C. S. G.; Catalão, C. H.; Juneyoung, J.; Ganesh, B.; Petronilho, F.; Dal-Pizzol, F.; Morales, R. and Barichello, T. “Sepsis exacerbates Alzheimer’s disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden”. Molecular Psychiatry. 2023. Accepted.
- Invited Articles in Journals (peer reviewed)
- Saá, P.; Castilla, J.; Morales, R.; Abid, K.; Maundrell, K. and Soto, C. “Protein Misfolding Cyclic Amplification for diagnosis and prion propagation studies” in Amyloid, Prions, and Other Protein Aggregates, Part B. Methods in Enzymology. 2006; 412: 3-21.
- Morales, R.; Abid, K.; and Soto, C. “The prion strain phenomenon: Molecular basis and unprecedented features”. Biochimica and Biophysica Acta. 2007; 1772 (6): 681-691.
- Morales, R.; Green, K.M.; and Soto, C. “Cross currents in protein misfolding disorders: interactions and therapy”. CNS & Neurological Disorders – Drug Targets. 2009; 8(5): 363-371.
- Morales, R.; Moreno-Gonzalez, I.; and Soto, C. “Cross-seeding of Misfolded Proteins: Implications for Etiology and Pathogenesis of Protein Misfolding Diseases”. PLOS Pathogens. 2013; 9(9): e1003537.
- Morales, R.; Callegari, K.; and Soto, C. “Prion-like features of misfolded Aβ and tau aggregates”. Virus Research. 2015; 207:106-112.
- Morales, R. “Prion strains in mammals: different conformations leading to disease”. PLOS Pathogens. 13(7): e1006323.
- Gomez-Gutierrez, R.; Morales, R. “The prion-like phenomenon in Alzheimer’s disease: evidence of pathology transmission in humans”. PLOS Pathogens. 2020; 16(10): e1009004.
- Yakubu, U.¥; Catumbela, C. S. G.¥; Morales, R.* and Morano, K.* “Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit”. Open Biology. 2020; 10: 200282. (*Corresponding authors).
- Barichello, T; Giridharan, V.V.; Comim, C.M., and Morales, R. “What is the role of microbial infection in Alzheimer’s disease”. Brazilian Journal of Psychiatry. 2022; 44(3): 245-247.
- Gamez, N. and Morales, R. “The role of circulating Aβ seeds in the progression of cerebral amyloidosis”. Neuroscience Insights. 2022; 17: 26331055221123072.
- Kelley, S.; Perez-Urrutia, N. and Morales, R. “Misfolded Aβ strains and their potential roles in the clinical and pathological variability of Alzheimer’s disease”. Neural Regeneration Research. 2023; 18(1): 119–120.
- Catumbela, C. S. G. and Morales, R. “Transmission of amyloid-β pathology in humans: a perspective on clinical evidence”. Neural Regeneration Research. Accepted.
- Kumar, V.; Morales, R. and Tsvetkov, A. S. “G-quadruplexes and associated proteins in aging and Alzheimer’s disease”. Frontiers in Aging. Accepted.
C) Editorials (peer reviewed)
- Moreno-Gonzalez, I.; Morales, R.; Baglietto-Vargas, D. and Sanchez-Varo, R. “Editorial: Risk factors for Alzheimer’s disease”. Frontiers in Aging Neuroscience. 2020. 12:124. doi: 10.3389/fnagi.2020.00124
- Generoso, J.S.; Morales, R. and Barichello, T. “Editorial: Biomarkers in Alzheimer’s disease: are we there yet?”. Brazilian Journal of Psychiatry. 2020. 42(4):337-339. doi:10.1590/1516-4446-2020-0013.
- Duran-Aniotz, C.; Moreno-Gonzalez, I.; Bilches-Medinas, D. and Morales, R. “Editorial: Protein misfolding and proteostasis impairment in aging and neurodegeneration: from spreading studies to therapeutic approaches”. Frontiers in Aging Neuroscience. 2022; 13:830779.
