Faculty Member
Professor
Department of Neurology
David Geffen School of Medicine
University of California, Los Angeles
710 Westwood Blvd.
Los Angeles, CA 90095
Faculty Member
Professor
Department of Medicine
Department of Neurology
David Geffen School of Medicine
University of California, Los Angeles
Center for Health Sciences
650 C. Young Dr. South,
Los Angeles, CA 90095
Lab: 44-127
Office: 44-146
Faculty Member
Professor in Residence
Chief, Neurobiology Research, Sepulveda VA Medical Center
Department of Psychiatry & Biobehavioral Sciences
David Geffen School of Medicine
University of California, Los Angeles
Bldg 7, Greater Los Angeles Health System, Sepulveda
16111 Plummer St, North Hills,
Los Angeles, CA 91343
Research:
Our primary interest is in understanding the evolution, function and disorders of sleep. We are analyzing the brainstem-forebrain interactions responsible for the control of muscle tone in waking and across the sleep cycle. This is of importance in understanding REM sleep behavior disorder, cataplexy and sleep apnea. We are studying the phylogeny of sleep by investigating the physiology and neurochemistry of sleep in reptiles, marine mammals and human hunter gatherers.
A major focus of the laboratory is on narcolepsy, its anatomy, pathophysiology and treatment. We found that human narcolepsy is linked to a loss of locus coeruleus and hypocretin neurons as well as changes in other neuronal groups. The loss of locus coeruleus neurons, which project both rostrally as part of the ascending reticular activating system, and caudally to spinal motor systems, can explain the unique symptoms of narcolepsy, sleepiness and cataplexy. The loss of hypocretin (orexin) neurons, which we find are linked to opioid addiction, can explain the elevated incidence of depression in narcolepsy. We are investigating ways of controlling and reversing the symptoms of narcolepsy in narcoleptic animals and in humans.
See two recent publications below:
Thannickal, T.C., Wu, Ming-Fung, Cornford, M.C. and Siegel, Jerome M., Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons. Nature Communications [PMID 41904178] 2026. https://doi.org/10.1038/s41467-026-70899-x
McGregor, R., Wu, Ming-Fung, Thannickal, T.C., Siegel, Jerome M. Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia. Nature Mental Health. PMCID: PMC11845277 NIHMSID: NIHMS2053716 PMID: 39989723, 2024
Publications
https://www.ncbi.nlm.nih.gov/myncbi/jerome.siegel.1/bibliography/public/
Contrary to some speculation in the media commenting on our recent locus coeruleus paper (above), we see no evidence that the loss of locus coeruleus neurons is responsible for “more severe narcolepsy.” Rather, we conclude that both the sleepiness and cataplexy of narcolepsy are likely due to the loss of locus coeruleus neurons. Locus coeruleus neurons have both ascending projections to the forebrain and descending projections to spinal cord motor neurons (PMID 32943779).
Hypocretin neurons are active in relation to elevated mood (PMID: 36564940: PMID 32963102; PMID: 39989723), not changes in sleepiness or muscle tone, the major symptoms of narcolepsy. The loss of hypocretin neurons may be responsible for the greatly elevated incidence of depression in narcolepsy.
Faculty Member
Associate Professor
Department of Nursing
School of Nursing
University of California, Los Angeles
5-238 Factor Building
700 Tiverton Dr,
Los Angeles, CA 90095
BOX 956919
Biography
Dr. Sokolow has a broad background in pharmacology and neurobiology of Alzheimer’s disease (AD), with specific training and expertise in molecular biology, clinical pharmacy and pharmacogenomics with emphasis in analyzing secondary data of drug response in the treatment of cognitive symptoms of AD and mild cognitive impairment (MCI). Her current research project focuses on the discovery of genetic polymorphisms associated with response to AD medications, such as donepezil and other acetylcholinesterase inhibitors. Areas of Scholarly Expertise and Interest: Alzheimer’s disease, genetics, pharmacogenomics, pharmacology and therapeutics, biomarkers, calcium signaling pathways.
Publications
A selected list of publications:
Sokolow Sophie, Li Xiaohui, Chen Lucia, Taylor Kent D, Rotter Jerome I, Rissman Robert A, Aisen Paul S, Apostolova Liana G Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment Journal of Alzheimer’s disease : JAD, 2017; 56(1): 229-237.
Casamassa Antonella, La Rocca Claudia, Sokolow Sophie, Herchuelz Andre, Matarese Giuseppe, Annunziato Lucio, Boscia Francesca Ncx3 gene ablation impairs oligodendrocyte precursor response and increases susceptibility to experimental autoimmune encephalomyelitis Glia, 2016; 64(7): 1124-37.
Sokolow Sophie, Henkins Kristen M, Bilousova Tina, Gonzalez Bianca, Vinters Harry V, Miller Carol A, Cornwell Lindsey, Poon Wayne W, Gylys Karen H Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer’s disease Journal of neurochemistry, 2015; 133(3): 368-79.
Apostolova Liana G, Hwang Kristy S, Avila David, Elashoff David, Kohannim Omid, Teng Edmond, Sokolow Sophie, Jack Clifford R, Jagust William J, Shaw Leslie, Trojanowski John Q, Weiner Michael W, Thompson Paul M, Thompson Paul M Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures Neurology, 2015; 84(7): 729-37.
Hohendanner Felix, Ljubojević Senka, MacQuaide Niall, Sacherer Michael, Sedej Simon, Biesmans Liesbeth, Wakula Paulina, Platzer Dieter, Sokolow Sophie, Herchuelz André, Antoons Gudrun, Sipido Karin, Pieske Burkert, Heinzel Frank R Intracellular dyssynchrony of diastolic cytosolic [Ca²⁺] decay in ventricular cardiomyocytes in cardiac remodeling and human heart failure Circulation research, 2013; 113(5): 527-38.
Molinaro Pasquale, Cataldi Mauro, Cuomo Ornella, Viggiano Davide, Pignataro Giuseppe, Sirabella Rossana, Secondo Agnese, Boscia Francesca, Pannaccione Anna, Scorziello Antonella, Sokolow Sophie, Herchuelz André, Di Renzo Gianfranco, Annunziato Lucio Genetically modified mice as a strategy to unravel the role played by the Na(+)/Ca (2+) exchanger in brain ischemia and in spatial learning and memory deficits Advances in experimental medicine and biology, 2013; 961: 213-22.
Henkins Kristen M, Sokolow Sophie, Miller Carol A, Vinters Harry V, Poon Wayne W, Cornwell Lindsey B, Saing Tommy, Gylys Karen Hoppens Extensive p-tau pathology and SDS-stable p-tau oligomers in Alzheimer’s cortical synapses Brain pathology (Zurich, Switzerland), 2012; 22(6): 826-33.
Pannaccione Anna, Secondo Agnese, Molinaro Pasquale, D’Avanzo Carla, Cantile Maria, Esposito Alba, Boscia Francesca, Scorziello Antonella, Sirabella Rossana, Sokolow Sophie, Herchuelz André, Di Renzo Gianfranco, Annunziato Lucio A new concept: Aβ1-42 generates a hyperfunctional proteolytic NCX3 fragment that delays caspase-12 activation and neuronal death The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(31): 10609-17.
Sokolow Sophie, Henkins Kristen M, Bilousova Tina, Miller Carol A, Vinters Harry V, Poon Wayne, Cole Gregory M, Gylys Karen Hoppens AD synapses contain abundant Aβ monomer and multiple soluble oligomers, including a 56-kDa assembly Neurobiology of aging, 2012; 33(8): 1545-55.
Boscia F, D’Avanzo C, Pannaccione A, Secondo A, Casamassa A, Formisano L, Guida N, Sokolow Sophie, Herchuelz André, Annunziato L Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs oligodendrocyte differentiation Cell death and differentiation, 2012; 19(4): 562-72.
Sokolow Sophie, Henkins Kristen M, Williams Iris A, Vinters Harry V, Schmid Ingrid, Cole Gregory M, Gylys Karen H Isolation of synaptic terminals from Alzheimer’s disease cortex Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2012; 81(3): 248-54.
Sokolow Sophie, Luu Sanh H, Nandy Karabi, Miller Carol A, Vinters Harry V, Poon Wayne W, Gylys Karen H Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer’s disease cortex Neurobiology of disease, 2012; 45(1): 381-7.
Ringman John M, Schulman Howard, Becker Chris, Jones Ted, Bai Yuchen, Immermann Fred, Cole Gregory, Sokolow Sophie, Gylys Karen, Geschwind Daniel H, Cummings Jeffrey L, Wan Hong I Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations Archives of neurology, 2012; 69(1): 96-104.
Nguidjoe Evrard, Sokolow Sophie, Bigabwa Serge, Pachera Nathalie, D’Amico Eva, Allagnat Florent, Vanderwinden Jean-Marie, Sener Abdullah, Manto Mario, Depreter Marianne, Mast Jan, Joanny Geraldine, Montanya Eduard, Rahier Jacques, Cardozo Alessandra K, Eizirik Décio L, Schurmans Stéphane, Herchuelz André Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass Diabetes, 2011; 60(8): 2076-85.
Molinaro Pasquale, Viggiano Davide, Nisticò Robert, Sirabella Rossana, Secondo Agnese, Boscia Francesca, Pannaccione Anna, Scorziello Antonella, Mehdawy Bisan, Sokolow Sophie, Herchuelz André, Di Renzo Gianfranco F, Annunziato Lucio Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-term potentiation and spatial learning and memory The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(20): 7312-21.
Sokolow Sophie, Luu Sanh H, Headley Alison J, Hanson Alecia Y, Kim Taeree, Miller Carol A, Vinters Harry V, Gylys Karen H High levels of synaptosomal Na(+)-Ca(2+) exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer’s disease Cell calcium, 2011; 49(4): 208-16.
Verwey N A, van der Flier W M, Blennow K, Clark C, Sokolow S, De Deyn P P, Galasko D, Hampel H, Hartmann T, Kapaki E, Lannfelt L, Mehta P D, Parnetti L, Petzold A, Pirttila T, Saleh L, Skinningsrud A, Swieten J C V, Verbeek M M, Wiltfang J, Younkin S, Scheltens P, Blankenstein M A A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease Annals of clinical biochemistry, 2009; 46(Pt 3): 235-40.
Wehling-Henricks Michelle, Sokolow Sophie, Lee Jamie J, Myung Kyu H, Villalta S Armando, Tidball James G Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy Human molecular genetics, 2008; 17(15): 2280-92.
Ringman J M, Younkin S G, Pratico D, Seltzer W, Cole G M, Geschwind D H, Rodriguez-Agudelo Y, Schaffer B, Fein J, Sokolow S, Rosario E R, Gylys K H, Varpetian A, Medina L D, Cummings J L Biochemical markers in persons with preclinical familial Alzheimer disease Neurology, 2008; 71(2): 85-92.
Fein Jeffrey A, Sokolow Sophie, Miller Carol A, Vinters Harry V, Yang Fusheng, Cole Gregory M, Gylys Karen Hoppens Co-localization of amyloid beta and tau pathology in Alzheimer’s disease synaptosomes The American journal of pathology, 2008; 172(6): 1683-92.
Jeffs Graham J, Meloni Bruno P, Sokolow Sophie, Herchuelz Andre, Schurmans Stéphane, Knuckey Neville W NCX3 knockout mice exhibit increased hippocampal CA1 and CA2 neuronal damage compared to wild-type mice following global cerebral ischemia Experimental neurology, 2008; 210(1): 268-73.
Molinaro Pasquale, Cuomo Ornella, Pignataro Giuseppe, Boscia Francesca, Sirabella Rossana, Pannaccione Anna, Secondo Agnese, Scorziello Antonella, Adornetto Annagrazia, Gala Rosaria, Viggiano Davide, Sokolow Sophie, Herchuelz Andre, Schurmans Stèphane, Di Renzo Gianfranco, Annunziato Lucio Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(5): 1179-84.
Sokolow Sophie, Manto Mario, Gailly Philippe, Molgó Jordi, Vandebrouck Clarisse, Vanderwinden Jean-Marie, Herchuelz Andre, Schurmans Stéphane Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3 The Journal of clinical investigation, 2004; 113(2): 265-73.