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1. The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism

Author

Bressan, Elisangela, Reed, Xylena, Bansal, Vikas, Hutchins, Elizabeth, Cobb, Melanie M, Webb, Michelle G, Alsop, Eric, Grenn, Francis P, Illarionova, Anastasia, Savytska, Natalia, Violich, Ivo, Broeer, Stefanie, Fernandes, Noémia, Sivakumar, Ramiyapriya, Beilina, Alexandra, Billingsley, Kimberley J, Berghausen, Joos, Pantazis, Caroline B, Pitz, Vanessa, Patel, Dhairya, Daida, Kensuke, Meechoovet, Bessie, Reiman, Rebecca, Courtright-Lim, Amanda, Logemann, Amber, Antone, Jerry, Barch, Mariya, Kitchen, Robert, Li, Yan, Dalgard, Clifton L, Center, The American Genome, Rizzu, Patrizia, Hernandez, Dena G, Hjelm, Brooke E, Nalls, Mike, Gibbs, J Raphael, Finkbeiner, Steven, Cookson, Mark R, Van Keuren-Jensen, Kendall, Craig, David W, Singleton, Andrew B, Heutink, Peter, and Blauwendraat, Cornelis

Subjects
Biological Sciences, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Neurosciences, Stem Cell Research, Aging, Parkinson's Disease, Neurodegenerative, Brain Disorders, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, American Genome Center, Parkinson disease, dopaminergic neurons, genetic risk, induced pluripotent stem cell, omics single-cell RNA sequencing single-cell ATAC sequencing SNCA LRRK2 GBA1
Abstract

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.

Published
2023

2. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author

Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martinez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernandez, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, and Morris, Huw R.

Published
2023
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3. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

Author

Okubadejo, Njideka, Ojo, Oluwadamilola, Abiodun, Oladunni, Achoru, Charles, Agabi, Osigwe, Agulanna, Uchechi, Akinyemi, Rufus, Ali, Mohammed, Ani-Osheku, Ifeyinwa, Arigbodi, Ohwotemu, Bello, Abiodun, Erameh, Cyril, Farombi, Temitope, Fawale, Michael, Imarhiagbe, Frank, Iwuozo, Emmanuel, Komolafe, Morenikeji, Nwani, Paul, Nwazor, Ernest, Nyandaiti, Yakub, Obiabo, Yahaya, Odeniyi, Olanike, Odiase, Francis, Ojini, Francis, Onwuegbuzie, Gerald, Osaigbovo, Godwin, Osemwegie, Nosakhare, Oshinaike, Olajumoke, Otubogun, Folajimi, Oyakhire, Shyngle, Ozomma, Simon, Samuel, Sarah, Taiwo, Funmilola, Wahab, Kolawole, Zubair, Yusuf, Gams Massi, Daniel, Gueumekane Bila lamou, Eric, Njamnshi Nfor, Leonard, Magnerou, Mélanie Annick, Fogang Fogoum, Yannick, Shalash, Ali, El-FawaI, Hassan, Khedr, Eman, Fawi, Gharib, A. Eltantawi, Mohamed, Salama, Mohamed, El-Jaafary, Shaimaa, Hamed, Sharifa, Tafesse Mengesha, Abenet, Alemayehu Ayele, Biniyam, Melka Oda, Dereje, Zenebe Zewde, Yared, Debebe Gelan, Yohanesse, AkpaIu, Albert, Charway-Felli, Augustina, Stephen Sarfo, Fred, Adjei, Patrick, Obese, Vida, Bocoum, Abdoulaye, Koita, Abdou, Oumar Guinto, Cheick, Coulibaly, Toumany, Maiga, Youssoufa, Kone, Zaynab, Bell, Abiodun, Adebowale, Akintunde A., Akpekpe, John, lyagba, Alagoma, Wulgo, Ali Mohammed, Arabambi, Babawale, Agu, Christian, Dike, Franklin, Ishola, Ismail, Abiodun, Kehinde, Ekenze, Oluchi, Agabi Osigwe, Paul, Balarabe, Salisu, Abubakar, Sani, Williams, Uduak, Fall, Maouly, Mamadou Diop, Alassane, Hilaire Dominique, Ewodo Touna, Mochan, Andre, Modi, Girish, Dindayal, Saiesha, Ali Awadelkareem, Eman, Elsayed, Inas, Dahawi, Maha, Awadelkareem, Mosab Ali, Misbah, Sarah, Mushengez, Brighton, Kimambo, Henrika, Msango, Leonard, Adebayo, Philip, OKeng, Kigocha, Diekker, Marieke, URassa, Sarah, Gouider, Riadh, Ben Djebara, Mouna, Gargouri, Amina, Kacem, Imen, Nasri, Amina, Mrabet, Saloua, Sghaier, Ikram, Mkada, Imen, Atadzhanov, Masharip, Chishimba, Lorraine, Rizig, Mie, Jama, Fatumah, Okunoye, Olaitan, Hardy, John, Houlden, Henry, Singleton, Andrew, Nalls, Mike, Shamim, Ejaz, Jonas, Cabell, Williamson, Jared, Hall, Deborah A., Rosenbaum, Marc, Davis, Staci, Dean, Marissa, Cromer, Candace, Smith, Jenna, Ruffrage, Lauren, Richardson, Joseph, Sipma, Rebeka, Xie, Tao, Padmanaban, Manesh, Warren, Natalie, Mercado, Tomas, Disbrow, Elizabeth, Chauppeta, Brian, Thomas-Dean, Fermine, Toms, Jamie, Lofton, Katelyn, Rawls, Ashley, Rizer, Kyle, Black, Nieci, Solle, Justin, O'Grady, Alyssa, Sherer, Todd, Fiske, Brian, Başak, A. Nazlı, Tan, Ai Huey, Noyce, Alastair, Akpalu, Albert, Espay, Alberto, Martínez-Carrasco, Alejandro, Medina, Alex, Zimprich, Alexander, Brice, Alexis, Karimova, Altynay, Hernandez, Alvaro, Illarionova, Anastasia, Quattrone, Andrea, Singleton, Andrew B, Sobering, Andrew K., Vinuela, Angel, Sanyaolu, Arinola, Schumacher-Schuh, Artur F., Kishore, Asha, Ahmad-Annuar, Azlina, Al Mubarak, Bashayer, Tang, Beisha, Pizarro Galleguillos, Benjamin, Jeon, Beomseok, Siddiqi, Bernadette, Casey, Bradford, Mollenhauer, Brit, Carroll, Camille, Rieder, Carlos, Pantazis, Caroline B., Comart, Charisse, Lin, Chin-Hsien, Klein, Christine, Bale, Claire, Shepherd, Claire E, Wegel, Claire, Blauwendraat, Cornelis, Vitale, Dan, Martinez-Ramirez, Daniel, Hall, Deborah, Hernandez, Dena, KP, Divya, Nguyen, Duan, Fon, Edward A., Dadiotis, Efthymios, Riley, Ekemini, Iakovenko, Elena, Stafford, Ellie, Gatto, Emilia M, Valente, Enza Maria, Vollstedt, Eva-Juliane, Faghri, Faraz, Genc, Gencer, Xiromerisiou, Georgia, Hadjigorgiou, Georgios, Hiu-Fai Chan, Germaine, Arboleda, Gonzalo, Kaishibayeva, Gulnaz, Höglinger, Günter, Leonard, Hampton, Madoev, Harutyun, Iwaki, Hirotaka, Chen, Honglei, Wu, Hsiu-Chuan, Shang, Huifang, Morris, Huw R, F. Mata, Ignacio, Keller Sarmiento, Ignacio Juan, Dagklis, Ioannis, Tarnanas, Ioannis, Aasly, Jan O., Hoenicka, Janet, Corvol, Jean-Christophe, Foo, Jia Nee, Guo, Jifeng, Junker, Johanna, Carr, Jonathan, Kim, Jonggeol Jeff, Orozco, Jorge, Jankovic, Joseph, Shulman, Joshua, Hunter, Julie, Solle, Justin C., Murphy, Kaileigh, Nuytemans, Karen, Kieburtz, Karl, Lohmann, Katja, Marek, Kenneth, Mok, Kin Ying, Kumar, Kishore, Levine, Kristin, Chahine, Lana M., Lange, Lara M., Pihlstrøm, Lasse, Screven, Laurel, Stefanis, Leonidas, Shulman, Lisa, Marsili, Luca, Parnetti, Lucilla, Kuhl, Maggie, Funayama, Manabu, Sharma, Manu, Tan, Manuela, Kauffman, Marcelo, Miranda, Marcelo, Bustamante, Maria Leonor, Stamelou, Maria, Periñan Tocino, Maria Teresa, Cornejo-Olivas, Mario, Jimenez del Rio, Marlene, Makarious, Mary B, Koretsky, Mathew, Rodriguez-Violante, Mayela, Ellis, Melina, Avenali, Micol, Rentería, Miguel E., Inca-Martines, Miguel z, Nalls, Mike A., Ibrahim Norlinah, Mohamed, Umair, Muhammad, Ip, Nancy, Louie, Naomi, Cheung, Nelson Yuk-Fai, Mencacci, Niccolò Emanuele, Wood, Nicholas, Williams, Nigel, Hattori, Nobutaka, Abdul Murad, Nor Azian, Ibrahim, Norlinah Mohamed, Monchi, Oury, Öztop Çakmak, Özgür, Öztop Çakmak, Patricio Öztop Çakmak, Lewis, Patrick Alfryn, Pastor, Pau, Reyes-Pérez, Paula, Saffie Awad, Paula, Chana, Pedro, Chan, Phillip, Kung, Pin-Jui, Chan, Piu, Pal, Pramod, Lingappa Kukkle, Prashanth, Ojha, Rajeev, Kaiyrzhanov, Rauan, Krüger, Rejko, Amouri, Rim, Weil, Rimona, Rajan, Roopa, Alcalay, Roy, Wu, Ruey-Meei, Borgohain, Rupam, Sassi, Samia Ben, Khachatryan, Samson, Bandres-Ciga, Sara, El-Sadig, Sarah, Wu, Serena, Groppa, Sergio, Azmin, Shahrul, Lim, Shen-Yang, Ur-Rehman, Shoaib, Ertan, Sibel, Stott, Simon, Jasaitye, Simona, Chowdhury, Sohini, Dumanis, Sonya, Bardien, Soraya, Lubbe, Steven, Koks, Sulev, Dey, Sumit, Foroud, Tatiana, Fon, Ted, Beach, Thomas, Gasser, Thomas, Anderson, Tim, Nguyen, Toan, Schirinzi, Tommaso, Shiraishi, Tomotaka, Pitcher, Toni, Tumas, Vitor, Mohamed, Wael, Kamel, Walaa A., Luo, Wei, Zhou, Xiaopu, Zewde, Yared Z., Song, Yeajin, Wen, Yi, Wu, Yihru, Joong Kim, Yun, Tavadyan, Zaruhi, Fang, Zih-Hua, Ojo, Oluwadamilola Omolara, Crea, Peter Wild, Abiodun, Oladunni Victoria, Levine, Kristin S, Abubakar, Sani Atta, Achoru, Charles Obiora, Adeniji, Olaleye Akinmola, Agabi, Osigwe Paul, Koretsky, Mathew J, Hall, Deborah A, Akinyemi, Rufus Olusola, Ali, Mohammed Wulgo, Shamim, Ejaz A, Padmanaban, Mahesh, Arigbodi, Ohwotemu Michael, Standaert, David G, Bello, Abiodun Hamzat, Dean, Marissa N, Erameh, Cyril Oshomah, Farombi, Temitope Hannah, Fawale, Michael Bimbola, Billingsley, Kimberley J, Imarhiagbe, Frank Aiwansoba, Jerez, Pilar Alvarez, Iwuozo, Emmanuel Uzodinma, Baker, Breeana, Komolafe, Morenikeji Adeyoyin, Malik, Laksh, Nwani, Paul Osemeke, Daida, Kensuke, Nwazor, Ernest Okwundu, Miano-Burkhardt, Abigail, Nyandaiti, Yakub Wilberforce, Obiabo, Yahaya Olugbo, Kluss, Jillian H, Odeniyi, Olanike Adedoyin, Hernandez, Dena G, Odiase, Francis Ehidiamen, Tayebi, Nahid, Ojini, Francis Ibe, Sidranksy, Ellen, Onwuegbuzie, Gerald Awele, D'Souza, Andrea M, Osaigbovo, Godwin Osawaru, Berhe, Bahafta, Reed, Xylena, Oshinaike, Olajumoke Olufemi, Leonard, Hampton L, Otubogun, Folajimi Morenikeji, Alvarado, Chelsea X, Oyakhire, Shyngle Imiewan, Ozomma, Simon Izuchukwu, Samuel, Sarah Chabiri, Taiwo, Funmilola Tolulope, Wahab, Kolawole Wasiu, Zubair, Yusuf Agboola, Kim, Jonggeol Jeffrey, Nalls, Mike A, Heilbron, Karl, Norcliffe-Kaufmann, Lucy, and Okubadejo, Njideka Ulunma

Published
2023
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6. Harnessing diversity to study Alzheimer’s disease: A new iPSC resource from the NIH CARD and ADNI

Author

Screven, Laurel A., primary, Pantazis, Caroline B., additional, Andersh, Katherine M., additional, Hong, Samantha, additional, Vitale, Dan, additional, Lara, Erika, additional, Ku, Ray Yueh, additional, Heutink, Peter, additional, Meyer, Jason, additional, Faber, Kelley, additional, Nho, Kwangsik, additional, Saykin, Andrew J., additional, Foroud, Tatiana M., additional, Nalls, Mike A., additional, Blauwendraat, Cornelis, additional, Singleton, Andrew, additional, and Narayan, Priyanka S., additional

Published
2024
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8. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

Author

Rizig, Mie, primary, Bandres-Ciga, Sara, additional, Makarious, Mary B, additional, Ojo, Oluwadamilola Omolara, additional, Crea, Peter Wild, additional, Abiodun, Oladunni Victoria, additional, Levine, Kristin S, additional, Abubakar, Sani Atta, additional, Achoru, Charles Obiora, additional, Vitale, Dan, additional, Adeniji, Olaleye Akinmola, additional, Agabi, Osigwe Paul, additional, Koretsky, Mathew J, additional, Agulanna, Uchechi, additional, Hall, Deborah A, additional, Akinyemi, Rufus Olusola, additional, Xie, Tao, additional, Ali, Mohammed Wulgo, additional, Shamim, Ejaz A, additional, Ani-Osheku, Ifeyinwa, additional, Padmanaban, Mahesh, additional, Arigbodi, Ohwotemu Michael, additional, Standaert, David G, additional, Bello, Abiodun Hamzat, additional, Dean, Marissa N, additional, Erameh, Cyril Oshomah, additional, Elsayed, Inas, additional, Farombi, Temitope Hannah, additional, Okunoye, Olaitan, additional, Fawale, Michael Bimbola, additional, Billingsley, Kimberley J, additional, Imarhiagbe, Frank Aiwansoba, additional, Jerez, Pilar Alvarez, additional, Iwuozo, Emmanuel Uzodinma, additional, Baker, Breeana, additional, Komolafe, Morenikeji Adeyoyin, additional, Malik, Laksh, additional, Nwani, Paul Osemeke, additional, Daida, Kensuke, additional, Nwazor, Ernest Okwundu, additional, Miano-Burkhardt, Abigail, additional, Nyandaiti, Yakub Wilberforce, additional, Fang, Zih-Hua, additional, Obiabo, Yahaya Olugbo, additional, Kluss, Jillian H, additional, Odeniyi, Olanike Adedoyin, additional, Hernandez, Dena G, additional, Odiase, Francis Ehidiamen, additional, Tayebi, Nahid, additional, Ojini, Francis Ibe, additional, Sidranksy, Ellen, additional, Onwuegbuzie, Gerald Awele, additional, D'Souza, Andrea M, additional, Osaigbovo, Godwin Osawaru, additional, Berhe, Bahafta, additional, Osemwegie, Nosakhare, additional, Reed, Xylena, additional, Oshinaike, Olajumoke Olufemi, additional, Leonard, Hampton L, additional, Otubogun, Folajimi Morenikeji, additional, Alvarado, Chelsea X, additional, Oyakhire, Shyngle Imiewan, additional, Ozomma, Simon Izuchukwu, additional, Samuel, Sarah Chabiri, additional, Taiwo, Funmilola Tolulope, additional, Wahab, Kolawole Wasiu, additional, Zubair, Yusuf Agboola, additional, Iwaki, Hirotaka, additional, Kim, Jonggeol Jeffrey, additional, Morris, Huw R, additional, Hardy, John, additional, Nalls, Mike A, additional, Heilbron, Karl, additional, Norcliffe-Kaufmann, Lucy, additional, Blauwendraat, Cornelis, additional, Houlden, Henry, additional, Singleton, Andrew, additional, Okubadejo, Njideka Ulunma, additional, Okubadejo, Njideka, additional, Ojo, Oluwadamilola, additional, Abiodun, Oladunni, additional, Achoru, Charles, additional, Agabi, Osigwe, additional, Akinyemi, Rufus, additional, Ali, Mohammed, additional, Arigbodi, Ohwotemu, additional, Bello, Abiodun, additional, Erameh, Cyril, additional, Farombi, Temitope, additional, Fawale, Michael, additional, Imarhiagbe, Frank, additional, Iwuozo, Emmanuel, additional, Komolafe, Morenikeji, additional, Nwani, Paul, additional, Nwazor, Ernest, additional, Nyandaiti, Yakub, additional, Obiabo, Yahaya, additional, Odeniyi, Olanike, additional, Odiase, Francis, additional, Ojini, Francis, additional, Onwuegbuzie, Gerald, additional, Osaigbovo, Godwin, additional, Oshinaike, Olajumoke, additional, Otubogun, Folajimi, additional, Oyakhire, Shyngle, additional, Ozomma, Simon, additional, Samuel, Sarah, additional, Taiwo, Funmilola, additional, Wahab, Kolawole, additional, Zubair, Yusuf, additional, Gams Massi, Daniel, additional, Gueumekane Bila lamou, Eric, additional, Njamnshi Nfor, Leonard, additional, Magnerou, Mélanie Annick, additional, Fogang Fogoum, Yannick, additional, Shalash, Ali, additional, El-FawaI, Hassan, additional, Khedr, Eman, additional, Fawi, Gharib, additional, A. Eltantawi, Mohamed, additional, Salama, Mohamed, additional, El-Jaafary, Shaimaa, additional, Hamed, Sharifa, additional, Tafesse Mengesha, Abenet, additional, Alemayehu Ayele, Biniyam, additional, Melka Oda, Dereje, additional, Zenebe Zewde, Yared, additional, Debebe Gelan, Yohanesse, additional, AkpaIu, Albert, additional, Charway-Felli, Augustina, additional, Stephen Sarfo, Fred, additional, Adjei, Patrick, additional, Obese, Vida, additional, Bocoum, Abdoulaye, additional, Koita, Abdou, additional, Oumar Guinto, Cheick, additional, Coulibaly, Toumany, additional, Maiga, Youssoufa, additional, Kone, Zaynab, additional, Bell, Abiodun, additional, Adebowale, Akintunde A., additional, Akpekpe, John, additional, lyagba, Alagoma, additional, Wulgo, Ali Mohammed, additional, Arabambi, Babawale, additional, Agu, Christian, additional, Dike, Franklin, additional, Ishola, Ismail, additional, Abiodun, Kehinde, additional, Ekenze, Oluchi, additional, Agabi Osigwe, Paul, additional, Balarabe, Salisu, additional, Abubakar, Sani, additional, Williams, Uduak, additional, Fall, Maouly, additional, Mamadou Diop, Alassane, additional, Hilaire Dominique, Ewodo Touna, additional, Mochan, Andre, additional, Modi, Girish, additional, Dindayal, Saiesha, additional, Ali Awadelkareem, Eman, additional, Dahawi, Maha, additional, Awadelkareem, Mosab Ali, additional, Misbah, Sarah, additional, Mushengez, Brighton, additional, Kimambo, Henrika, additional, Msango, Leonard, additional, Adebayo, Philip, additional, OKeng, Kigocha, additional, Diekker, Marieke, additional, URassa, Sarah, additional, Gouider, Riadh, additional, Ben Djebara, Mouna, additional, Gargouri, Amina, additional, Kacem, Imen, additional, Nasri, Amina, additional, Mrabet, Saloua, additional, Sghaier, Ikram, additional, Mkada, Imen, additional, Atadzhanov, Masharip, additional, Chishimba, Lorraine, additional, Rizig, Mie, additional, Jama, Fatumah, additional, Nalls, Mike, additional, Shamim, Ejaz, additional, Jonas, Cabell, additional, Williamson, Jared, additional, Hall, Deborah A., additional, Rosenbaum, Marc, additional, Davis, Staci, additional, Dean, Marissa, additional, Cromer, Candace, additional, Smith, Jenna, additional, Ruffrage, Lauren, additional, Richardson, Joseph, additional, Sipma, Rebeka, additional, Padmanaban, Manesh, additional, Warren, Natalie, additional, Mercado, Tomas, additional, Disbrow, Elizabeth, additional, Chauppeta, Brian, additional, Thomas-Dean, Fermine, additional, Toms, Jamie, additional, Lofton, Katelyn, additional, Rawls, Ashley, additional, Rizer, Kyle, additional, Black, Nieci, additional, Solle, Justin, additional, O'Grady, Alyssa, additional, Sherer, Todd, additional, Fiske, Brian, additional, Başak, A. Nazlı, additional, Tan, Ai Huey, additional, Noyce, Alastair, additional, Akpalu, Albert, additional, Espay, Alberto, additional, Martínez-Carrasco, Alejandro, additional, Medina, Alex, additional, Zimprich, Alexander, additional, Brice, Alexis, additional, Karimova, Altynay, additional, Hernandez, Alvaro, additional, Illarionova, Anastasia, additional, Quattrone, Andrea, additional, Singleton, Andrew B, additional, Sobering, Andrew K., additional, Vinuela, Angel, additional, Sanyaolu, Arinola, additional, Schumacher-Schuh, Artur F., additional, Kishore, Asha, additional, Ahmad-Annuar, Azlina, additional, Al Mubarak, Bashayer, additional, Tang, Beisha, additional, Pizarro Galleguillos, Benjamin, additional, Jeon, Beomseok, additional, Siddiqi, Bernadette, additional, Casey, Bradford, additional, Mollenhauer, Brit, additional, Carroll, Camille, additional, Rieder, Carlos, additional, Pantazis, Caroline B., additional, Comart, Charisse, additional, Lin, Chin-Hsien, additional, Klein, Christine, additional, Bale, Claire, additional, Shepherd, Claire E, additional, Wegel, Claire, additional, Martinez-Ramirez, Daniel, additional, Hall, Deborah, additional, Hernandez, Dena, additional, KP, Divya, additional, Nguyen, Duan, additional, Fon, Edward A., additional, Dadiotis, Efthymios, additional, Riley, Ekemini, additional, Iakovenko, Elena, additional, Stafford, Ellie, additional, Gatto, Emilia M, additional, Valente, Enza Maria, additional, Vollstedt, Eva-Juliane, additional, Faghri, Faraz, additional, Genc, Gencer, additional, Xiromerisiou, Georgia, additional, Hadjigorgiou, Georgios, additional, Hiu-Fai Chan, Germaine, additional, Arboleda, Gonzalo, additional, Kaishibayeva, Gulnaz, additional, Höglinger, Günter, additional, Leonard, Hampton, additional, Madoev, Harutyun, additional, Chen, Honglei, additional, Wu, Hsiu-Chuan, additional, Shang, Huifang, additional, F. Mata, Ignacio, additional, Keller Sarmiento, Ignacio Juan, additional, Dagklis, Ioannis, additional, Tarnanas, Ioannis, additional, Aasly, Jan O., additional, Hoenicka, Janet, additional, Corvol, Jean-Christophe, additional, Foo, Jia Nee, additional, Guo, Jifeng, additional, Junker, Johanna, additional, Carr, Jonathan, additional, Kim, Jonggeol Jeff, additional, Orozco, Jorge, additional, Jankovic, Joseph, additional, Shulman, Joshua, additional, Hunter, Julie, additional, Solle, Justin C., additional, Murphy, Kaileigh, additional, Nuytemans, Karen, additional, Kieburtz, Karl, additional, Lohmann, Katja, additional, Marek, Kenneth, additional, Mok, Kin Ying, additional, Kumar, Kishore, additional, Levine, Kristin, additional, Chahine, Lana M., additional, Lange, Lara M., additional, Pihlstrøm, Lasse, additional, Screven, Laurel, additional, Stefanis, Leonidas, additional, Shulman, Lisa, additional, Marsili, Luca, additional, Parnetti, Lucilla, additional, Kuhl, Maggie, additional, Funayama, Manabu, additional, Sharma, Manu, additional, Tan, Manuela, additional, Kauffman, Marcelo, additional, Miranda, Marcelo, additional, Bustamante, Maria Leonor, additional, Stamelou, Maria, additional, Periñan Tocino, Maria Teresa, additional, Cornejo-Olivas, Mario, additional, Jimenez del Rio, Marlene, additional, Koretsky, Mathew, additional, Rodriguez-Violante, Mayela, additional, Ellis, Melina, additional, Avenali, Micol, additional, Rentería, Miguel E., additional, Inca-Martines, Miguel z, additional, Nalls, Mike A., additional, Ibrahim Norlinah, Mohamed, additional, Umair, Muhammad, additional, Ip, Nancy, additional, Louie, Naomi, additional, Cheung, Nelson Yuk-Fai, additional, Mencacci, Niccolò Emanuele, additional, Wood, Nicholas, additional, Williams, Nigel, additional, Hattori, Nobutaka, additional, Abdul Murad, Nor Azian, additional, Ibrahim, Norlinah Mohamed, additional, Monchi, Oury, additional, Öztop Çakmak, Özgür, additional, Öztop Çakmak, Patricio Öztop Çakmak, additional, Lewis, Patrick Alfryn, additional, Pastor, Pau, additional, Reyes-Pérez, Paula, additional, Saffie Awad, Paula, additional, Chana, Pedro, additional, Chan, Phillip, additional, Kung, Pin-Jui, additional, Chan, Piu, additional, Pal, Pramod, additional, Lingappa Kukkle, Prashanth, additional, Ojha, Rajeev, additional, Kaiyrzhanov, Rauan, additional, Krüger, Rejko, additional, Amouri, Rim, additional, Weil, Rimona, additional, Rajan, Roopa, additional, Alcalay, Roy, additional, Wu, Ruey-Meei, additional, Borgohain, Rupam, additional, Sassi, Samia Ben, additional, Khachatryan, Samson, additional, El-Sadig, Sarah, additional, Wu, Serena, additional, Groppa, Sergio, additional, Azmin, Shahrul, additional, Lim, Shen-Yang, additional, Ur-Rehman, Shoaib, additional, Ertan, Sibel, additional, Stott, Simon, additional, Jasaitye, Simona, additional, Chowdhury, Sohini, additional, Dumanis, Sonya, additional, Bardien, Soraya, additional, Lubbe, Steven, additional, Koks, Sulev, additional, Dey, Sumit, additional, Foroud, Tatiana, additional, Fon, Ted, additional, Beach, Thomas, additional, Gasser, Thomas, additional, Anderson, Tim, additional, Nguyen, Toan, additional, Schirinzi, Tommaso, additional, Shiraishi, Tomotaka, additional, Pitcher, Toni, additional, Tumas, Vitor, additional, Mohamed, Wael, additional, Kamel, Walaa A., additional, Luo, Wei, additional, Zhou, Xiaopu, additional, Zewde, Yared Z., additional, Song, Yeajin, additional, Wen, Yi, additional, Wu, Yihru, additional, Joong Kim, Yun, additional, and Tavadyan, Zaruhi, additional

Published
2023
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10. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author

National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), Periñán, María Teresa, National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), and Periñán, María Teresa

Abstract

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia.

Published
2023

11. A Fully Automated FAIMS-DIA Mass Spectrometry-Based Proteomic Pipeline

Author

Reilly, Luke, primary, Lara, Erika, additional, Ramos, Daniel M., additional, Li, Ziyi, additional, Pantazis, Caroline B., additional, Stadler, Julia, additional, Santiana, Marianita, additional, Roberts, Jessica, additional, Faghri, Faraz, additional, Nalls, Mike A., additional, Narayan, Priyanka, additional, Liu, Yansheng, additional, Singleton, Andrew B., additional, Cookson, Mark R., additional, Ward, Michael E., additional, and Qi, Yue, additional

Published
2023
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12. A reference human induced pluripotent stem cell line for large-scale collaborative studies

Author

Pantazis, Caroline B., primary, Yang, Andrian, additional, Lara, Erika, additional, McDonough, Justin A., additional, Blauwendraat, Cornelis, additional, Peng, Lirong, additional, Oguro, Hideyuki, additional, Kanaujiya, Jitendra, additional, Zou, Jizhong, additional, Sebesta, David, additional, Pratt, Gretchen, additional, Cross, Erin, additional, Blockwick, Jeffrey, additional, Buxton, Philip, additional, Kinner-Bibeau, Lauren, additional, Medura, Constance, additional, Tompkins, Christopher, additional, Hughes, Stephen, additional, Santiana, Marianita, additional, Faghri, Faraz, additional, Nalls, Mike A., additional, Vitale, Daniel, additional, Ballard, Shannon, additional, Qi, Yue A., additional, Ramos, Daniel M., additional, Anderson, Kailyn M., additional, Stadler, Julia, additional, Narayan, Priyanka, additional, Papademetriou, Jason, additional, Reilly, Luke, additional, Nelson, Matthew P., additional, Aggarwal, Sanya, additional, Rosen, Leah U., additional, Kirwan, Peter, additional, Pisupati, Venkat, additional, Coon, Steven L., additional, Scholz, Sonja W., additional, Priebe, Theresa, additional, Öttl, Miriam, additional, Dong, Jian, additional, Meijer, Marieke, additional, Janssen, Lara J.M., additional, Lourenco, Vanessa S., additional, van der Kant, Rik, additional, Crusius, Dennis, additional, Paquet, Dominik, additional, Raulin, Ana-Caroline, additional, Bu, Guojun, additional, Held, Aaron, additional, Wainger, Brian J., additional, Gabriele, Rebecca M.C., additional, Casey, Jackie M., additional, Wray, Selina, additional, Abu-Bonsrah, Dad, additional, Parish, Clare L., additional, Beccari, Melinda S., additional, Cleveland, Don W., additional, Li, Emmy, additional, Rose, Indigo V.L., additional, Kampmann, Martin, additional, Calatayud Aristoy, Carles, additional, Verstreken, Patrik, additional, Heinrich, Laurin, additional, Chen, Max Y., additional, Schüle, Birgitt, additional, Dou, Dan, additional, Holzbaur, Erika L.F., additional, Zanellati, Maria Clara, additional, Basundra, Richa, additional, Deshmukh, Mohanish, additional, Cohen, Sarah, additional, Khanna, Richa, additional, Raman, Malavika, additional, Nevin, Zachary S., additional, Matia, Madeline, additional, Van Lent, Jonas, additional, Timmerman, Vincent, additional, Conklin, Bruce R., additional, Johnson Chase, Katherine, additional, Zhang, Ke, additional, Funes, Salome, additional, Bosco, Daryl A., additional, Erlebach, Lena, additional, Welzer, Marc, additional, Kronenberg-Versteeg, Deborah, additional, Lyu, Guochang, additional, Arenas, Ernest, additional, Coccia, Elena, additional, Sarrafha, Lily, additional, Ahfeldt, Tim, additional, Marioni, John C., additional, Skarnes, William C., additional, Cookson, Mark R., additional, Ward, Michael E., additional, and Merkle, Florian T., additional

Published
2022
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13. A reference human induced pluripotent stem cell line for collaborative studies

Author

Pantazis, Caroline B, Yang, Andrian, Lara, Erika, McDonough, Justin A, Blauwendraat, Cornelis, Peng, Lirong, Oguro, Hideyuki, Kanaujiya, Jitendra, Zou, Jizhong, Sebesta, David, Pratt, Gretchen, Cross, Erin, Blockwick, Jeffrey, Buxton, Philip, Kinner-Bibeau, Lauren, Medura, Constance, Tompkins, Christopher, Hughes, Stephen, Santiana, Marianita, Faghri, Faraz, Nalls, Mike A, Vitale, Daniel, Ballard, Shannon, Qi, Yue A, Ramos, Daniel M, Anderson, Kailyn M, Stadler, Julia, Narayan, Priyanka, Papademetriou, Jason, Reilly, Luke, Nelson, Matthew P, Aggarwal, Sanya, Rosen, Leah U, Kirwan, Peter, Pisupati, Venkat, Coon, Steven L, Scholz, Sonja W, Priebe, Theresa, Ottl, Miriam, Dong, Jian, Meijer, Marieke, Janssen, Lara JM, Lourenco, Vanessa S, van der Kant, Rik, Crusius, Dennis, Paquet, Dominik, Raulin, Ana-Caroline, Bu, Guojun, Held, Aaron, Wainger, Brian J, Gabriele, Rebecca MC, Casey, Jackie M, Wray, Selina, Abu-Bonsrah, Dad, Parish, Clare L, Beccari, Melinda S, Cleveland, Don W, Li, Emmy, Rose, Indigo VL, Kampmann, Martin, Aristoy, Carles Calatayud, Verstreken, Patrik, Heinrich, Laurin, Chen, Max Y, Schule, Birgitt, Dou, Dan, Holzbaur, Erika LF, Zanellati, Maria Clara, Basundra, Richa, Deshmukh, Mohanish, Cohen, Sarah, Khanna, Richa, Raman, Malavika, Nevin, Zachary S, Matia, Madeline, Van Lent, Jonas, Timmerman, Vincent, Conklin, Bruce R, Chase, Katherine Johnson, Zhang, Ke, Funes, Salome, Bosco, Daryl A, Erlebach, Lena, Welzer, Marc, Kronenberg-Versteeg, Deborah, Lyu, Guochang, Arenas, Ernest, Coccia, Elena, Sarrafha, Lily, Ahfeldt, Tim, Marioni, John C, Skarnes, William C, Cookson, Mark R, Ward, Michael E, and Merkle, Florian T

Subjects
Science & Technology, Cell Biology, DOPAMINE NEURONS, RISK LOCI, GENE, DISEASE, DIRECTIONAL GENOMIC HYBRIDIZATION, COPY NUMBER, DIFFERENTIATION, Cell & Tissue Engineering, HETEROGENEITY, Life Sciences & Biomedicine, A-BETA, GENERATION
Abstract

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field. ispartof: CELL STEM CELL vol:29 issue:12 pages:1685-+ ispartof: location:United States status: published

Published
2022

14. A reference human induced pluripotent stem cell line for large-scale collaborative studies

Author

Pantazis, Caroline B., Bu, Guojun, Skarnes, William C., Cookson, Mark R., Ward, Michael E., Merkle, Florian T., Pantazis, Caroline B., Bu, Guojun, Skarnes, William C., Cookson, Mark R., Ward, Michael E., and Merkle, Florian T.

Abstract

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

Published
2022

15. A reference induced pluripotent stem cell line for large-scale collaborative studies

Author

Pantazis, Caroline B., primary, Yang, Andrian, additional, Lara, Erika, additional, McDonough, Justin A., additional, Blauwendraat, Cornelis, additional, Peng, Lirong, additional, Oguro, Hideyuki, additional, Kanaujiya, Jitendra, additional, Zou, Jizhong, additional, Sebesta, David, additional, Pratt, Gretchen, additional, Cross, Erin, additional, Blockwick, Jeffrey, additional, Buxton, Philip, additional, Kinner-Bibeau, Lauren, additional, Medura, Constance, additional, Tompkins, Christopher, additional, Hughes, Stephen, additional, Santiana, Marianita, additional, Faghri, Faraz, additional, Nalls, Mike A., additional, Vitale, Daniel, additional, Ballard, Shannon, additional, Qi, Yue A., additional, Ramos, Daniel M., additional, Anderson, Kailyn M., additional, Stadler, Julia, additional, Narayan, Priyanka, additional, Papademetriou, Jason, additional, Reilly, Luke, additional, Nelson, Matthew P., additional, Aggarwal, Sanya, additional, Rosen, Leah U., additional, Kirwan, Peter, additional, Pisupati, Venkat, additional, Coon, Steven L., additional, Scholz, Sonja W., additional, Priebe, Theresa, additional, Öttl, Miriam, additional, Dong, Jian, additional, Meijer, Marieke, additional, Janssen, Lara J.M., additional, Lourenco, Vanessa S., additional, van der Kant, Rik, additional, Crusius, Dennis, additional, Paquet, Dominik, additional, Raulin, Ana-Caroline, additional, Bu, Guojun, additional, Held, Aaron, additional, Wainger, Brian J., additional, Gabriele, Rebecca M.C., additional, Casey, Jackie M, additional, Wray, Selina, additional, Abu-Bonsrah, Dad, additional, Parish, Clare L., additional, Beccari, Melinda S., additional, Cleveland, Don W., additional, Li, Emmy, additional, Rose, Indigo V.L., additional, Kampmann, Martin, additional, Aristoy, Carles Calatayud, additional, Verstreken, Patrik, additional, Heinrich, Laurin, additional, Chen, Max Y., additional, Schüle, Birgitt, additional, Dou, Dan, additional, Holzbaur, Erika L.F., additional, Zanellati, Maria Clara, additional, Basundra, Richa, additional, Deshmukh, Mohanish, additional, Cohen, Sarah, additional, Khanna, Richa, additional, Raman, Malavika, additional, Nevin, Zachary S., additional, Matia, Madeline, additional, Lent, Jonas Van, additional, Timmerman, Vincent, additional, Conklin, Bruce R., additional, Chase, Katherine Johnson, additional, Zhang, Ke, additional, Funes, Salome, additional, Bosco, Daryl A., additional, Erlebach, Lena, additional, Welzer, Marc, additional, Kronenberg-Versteeg, Deborah, additional, Lyu, Guochang, additional, Arenas, Ernest, additional, Coccia, Elena, additional, Sarrafha, Lily, additional, Ahfeldt, Tim, additional, Marioni, John C., additional, Skarnes, William C., additional, Cookson, Mark R., additional, Ward, Michael E., additional, and Merkle, Florian T., additional

Published
2021
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16. A fully automated FAIMS-DIA proteomic pipeline for high-throughput characterization of iPSC-derived neurons

Author

Reilly, Luke, primary, Peng, Lirong, additional, Lara, Erika, additional, Ramos, Daniel, additional, Fernandopulle, Michael, additional, Pantazis, Caroline B., additional, Stadler, Julia, additional, Santiana, Marianita, additional, Dadu, Anant, additional, Iben, James, additional, Faghri, Faraz, additional, Nalls, Mike A., additional, Coon, Steven L., additional, Narayan, Priyanka, additional, Singleton, Andrew B., additional, Cookson, Mark R., additional, Ward, Michael E., additional, and Qi, Yue A., additional

Published
2021
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20. Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system

Author

Pantazis, Caroline B.

Subjects
nervous system, mental disorders, psychological phenomena and processes
Abstract

Drug addiction is a disorder characterized by pathological motivation for drug. Our laboratory has recently developed a behavioral economics (BE) paradigm that uniquely assesses demand for drugs of abuse. Animals’ individual lever-pressing data can be fitted to demand curves to determine two important measures of cocaine demand: baseline consumption (Q0) and motivation (α). As α is the slope of the demand curve, it inversely scales with motivation, such that animals with greater demand elasticity (α) have lower motivation for cocaine. Here, we utilized our BE paradigm with pharmacological, morpholino antisense, and retrograde tracing approaches and determined that lateral septum (LS) and lateral hypothalamus (LH) orexin neurons are important neuronal populations for cocaine demand elasticity (α).We demonstrate that inhibiting LS reduced motivation (increased demand elasticity; α) and that the benzodiazepine diazepam blocked this effect, pointing to opposing roles of the two manipulations on ventral tegmental area (VTA) dopamine signaling. The two manipulations were similarly found to be anxiolytic, indicating that changes in drug taking occurred independently of effects on anxiety. Similarly, we show that orexin signaling contributes to motivation for cocaine (α) and that the involvement of orexin in motivated drug taking is mediated primarily by orexin neurons in LH. Animals sacrificed after BE had greater expression of orexin neurons in LH, and unilateral knockdown of LH orexin cells attenuated motivation during BE. The number of spared LH orexin neurons predicted α value in antisense-infused animals and in animals sacrificed two weeks after BE testing. We then blocked orexin-1 receptor signaling in VTA using the oreceptor antagonist SB-334867 (SB) and found that intra-VTA SB reduced motivation. The effects of SB specifically occurred in animals trained and tested on BE with cues and removing cocaine-paired cues reduced SB efficacy. Finally, using retrograde tract tracing, we observed that a greater proportion of LH orexin neurons project to VTA than do other subregions of the orexin cell field.Collectively, these studies implicate two important neuronal populations in motivation for cocaine and indicate that both LS and LH orexin connections to the mesolimbic dopamine system mediate their effects on motivation.

Published
2019
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25. The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand.

Author

Pantazis, Caroline B., James, Morgan H., Bentzley, Brandon S., Aston‐Jones, Gary, and Aston-Jones, Gary

Subjects
*INDIVIDUAL differences, *ELASTICITY (Economics), *COCAINE, *NEURONS, *HYPOTHALAMUS, *PREOPTIC area
Abstract

Lateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in motivation (demand) for cocaine in our behavioral economics (BE) paradigm, and whether knockdown of these cells predicted changes in economic demand. We quantified LH orexin cell numbers in animals immediately following our BE paradigm, as well as after a 2-week period of abstinence, to relate the number of LH orexin cells to economic demand for cocaine. We also knocked down LH orexin expression with an orexin morpholino antisense to determine how reduced orexin numbers impacted cocaine demand. We found that animals with greater baseline motivation for cocaine (lower demand elasticity) had more LH orexin neurons. Following a 2-week abstinence from cocaine, the number of LH orexin neurons predicted economic demand for cocaine prior to abstinence, indicating that orexin expression is a persistent marker for demand. Reducing LH orexin cell numbers with antisense decreased motivation for cocaine (increased demand elasticity) without affecting baseline consumption. In addition, the number of spared LH orexin neurons after antisense treatment correlated with individual motivation for cocaine. These studies point to a role for the endogenous number of LH orexin neurons in individual differences in motivation for cocaine. [ABSTRACT FROM AUTHOR]

Published
2020
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27. Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam.

Author

Pantazis, Caroline B., Aston‐Jones, Gary, and Aston-Jones, Gary

Subjects
*DOPAMINERGIC neurons, *COCAINE, *PHARMACOLOGY, *ELASTICITY (Economics), *TREATMENT effectiveness, *PREOPTIC area, *ANIMAL behavior, *ANIMALS, *BIOLOGICAL models, *DIAZEPAM, *DOPAMINE uptake inhibitors, *MOTIVATION (Psychology), *RATS, *SUBSTANCE abuse, *TELENCEPHALON, *GABA modulators, *PHARMACODYNAMICS
Abstract

The lateral septum (LS) is a brain region implicated in motivation, addiction, anxiety, and affect. We recently found that LS is necessary for cocaine-seeking behaviors including conditioned place preference and reinstatement of extinguished drug seeking, which involve LS input to limbic regions including ventral tegmental area (VTA) and orexin neurons in hypothalamus. Here, we microinjected baclofen-muscimol (B-M) in LS prior to testing in a behavioral economics (BE) paradigm. We found that intra-LS B-M decreased motivation (increased demand elasticity; α) for cocaine, but did not change consumption at low effort (Q0 ). We also compared the effects of LS inhibition with the effects of treatment with the benzodiazepine diazepam, which has been shown to facilitate reward pathways and disinhibit VTA dopamine neurons. Pretreatment with diazepam blocked the effects of LS inhibition and restored cocaine demand to that following vehicle treatment. These changes in cocaine demand after LS inhibition or diazepam were not due to effects on anxiety, as both manipulations produced similar effects on anxiety measures but opposing effects on drug taking. Collectively, these studies point to LS as a critical region driving motivation for cocaine, likely through its interactions with the mesolimbic dopamine system. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Drug addiction co-morbidity with alcohol: Neurobiological insights.

Author

McGinn MA, Pantazis CB, Tunstall BJ, Marchette RCN, Carlson ER, Said N, Koob GF, and Vendruscolo LF

Subjects
Comorbidity, Humans, Alcoholism epidemiology, Alcoholism physiopathology, Substance-Related Disorders epidemiology, Substance-Related Disorders physiopathology
Abstract

Addiction is a chronic disorder that consists of a three-stage cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages involve, respectively, neuroadaptations in brain circuits involved in incentive salience and habit formation, stress surfeit and reward deficit, and executive function. Much research on addiction focuses on the neurobiology underlying single drug use. However, alcohol use disorder (AUD) can be co-morbid with substance use disorder (SUD), called dual dependence. The limited epidemiological data on dual dependence indicates that there is a large population of individuals suffering from addiction who are dependent on more than one drug and/or alcohol, yet dual dependence remains understudied in addiction research. Here, we review neurobiological data on neurotransmitter and neuropeptide systems that are known to contribute to addiction pathology and how the involvement of these systems is consistent or divergent across drug classes. In particular, we highlight the dopamine, opioid, corticotropin-releasing factor, norepinephrine, hypocretin/orexin, glucocorticoid, neuroimmune signaling, endocannabinoid, glutamate, and GABA systems. We also discuss the limited research on these systems in dual dependence. Collectively, these studies demonstrate that the use of multiple drugs can produce neuroadaptations that are distinct from single drug use. Further investigation into the neurobiology of dual dependence is necessary to develop effective treatments for addiction to multiple drugs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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