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1. A consensus protocol for functional connectivity analysis in the rat brain

Author

Grandjean, J., Desrosiers-Gregoire, G., Anckaerts, C., Angeles-Valdez, D., Ayad, F., Barrière, D., Blockx, I., Bortel, A., Broadwater, M., Cardoso, B., Célestine, M., Chavez-Negrete, J., Choi, S., Christiaen, E., Clavijo, P., Colon-Perez, L., Cramer, S., Daniele, T., Dempsey, E., Diao, Y., Doelemeyer, A., Dopfel, D., Dvořáková, L., Falfán-Melgoza, C., Fernandes, F., Fowler, C., Fuentes-Ibañez, A., Garin, C., Gelderman, E., Golden, C., Guo, C., Henckens, M., Hennessy, L., Herman , P., Hofwijks, N., Horien, C., Ionescu, T., Jones, J., Kaesser, J., Kim, E., Lambers, H., Lazari, A., Lee, S., Lillywhite, A., Liu, Y., López-Castro, A., López-Gil , X., Ma, Z., MacNicol, E., Madularu, D., Mandino, F., Marciano, S., McAuslan, M., McCunn, P., McIntosh, A., Meng, X., Meyer-Baese, L., Missault, S., Moro, F., Naessens, D., Nava-Gomez, L., Nonaka, H., Ortiz, J., Paasonen, J., Pais-Roldán, P., Peeters, L., Pereira, M., Perez, P., Pompilus, M., Prior, M., Rakhmatullin, R., Reimann, H., Reinwald, J., Triana Del Rio, R., Rivera-Olvera, A., Ruiz-Pérez, D., Russo, G., Rutten, T., Ryoke, R., Sack, M., Salvan, P., Sanganahalli, B., Schroeter, A., Seewoo , B., Selingue, E., Seuwen, A., Shi, B., Sirmpilatze, N., Smith, J., Smith, C., Sobczak, F., Stenroos, P., Straathof, M., Strobelt, S., Sumiyoshi, A., Takahashi, K., Torres-García, M., Tudela, R., van den Berg, M., van der Marel, K., van Hout, A., Vertullo, R., Vidal, B., Vrooman, R., Wang, X., Wank, I., Watson, D., Yin, T., Zhang, Y., Zurbruegg, S., Achard, S., Alcauter, S., Auer, D., Barbier, E., Baudewig, J., Beckmann, C., Beckmann, N., Becq, G., Blezer, E., Bolbos, R., Boretius, S., Bouvard, S., Budinger, E., Buxbaum, J., Cash, D., Chapman, V., Chuang, K., Ciobanu, L., Coolen, B., Dalley, J., Dhenain, M., Dijkhuizen, R., Esteban, O., Faber, C., Febo, M., Feindel, K., Forloni, G., Fouquet, J., Garza-Villarreal, E., Gass, N., Glennon, J., Gozzi, A., Gröhn, O., Harkin, A., Heerschap, A., Helluy, X., Herfert , K., Heuser, A., Homberg, J., Houwing, D., Hyder, F., Ielacqua, G., Jelescu, I., Johansen-Berg, H., Kaneko, G., Kawashima, R., Keilholz, S., Keliris, G., Kelly, C., Kerskens, C., Khokhar, J., Kind, P., Langlois, J., Lerch, J., López-Hidalgo, M., Manahan-Vaughan, D., Marchand, F., Mars, R., Marsella, G., Micotti , E., Muñoz-Moreno , E., Near, J., Niendorf, T., Otte, W., Pan , W., Prado-Alcalá, R., Quirarte, G., Rodger , J., Rosenow, T., Sampaio-Baptista, C., Sartorius, A., Sawiak, S., Scheenen, T., Shemesh, Shih, Y., Shmuel, A., Soria, G., Stoop, R., Thompson, G., Till, S., Todd, N., Van Der Linden, A., van der Toorn, A., van Tilborg, G., Vanhove, C., Veltien, A., Verhoye, M., Wachsmuth, L., Weber-Fahr, W., Wenk , P., Yu, X., Zerbi , V., Zhang , N., Zhang, B., Zimmer, L., Devenyi, G., Chakravarty, M., and Hess, A.

Subjects
Action, intention, and motor control, General Neuroscience, fmri, Medizin, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Human medicine
Abstract

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience. The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Published
2023

2. Author Correction: A consensus protocol for functional connectivity analysis in the rat brain

Author

Grandjean, J., Desrosiers-Gregoire, G., Anckaerts, C., Angeles-Valdez, D., Ayad, F., Barrière, D., Blockx, I., Bortel, A., Broadwater, M., Cardoso, B., Célestine, M., Chavez-Negrete, J., Choi, S., https://orcid.org/0000-0001-7327-1344, Christiaen, E., Clavijo, P., Colon-Perez, L., Cramer, S., Daniele, T., Dempsey, E., Diao, Y., Doelemeyer, A., Dopfel, D., Dvořáková, L., Falfán-Melgoza, C., Fernandes, F., Fowler, C., Fuentes-Ibañez, A., Garin, C., Gelderman, E., Golden, C., Guo, C., Henckens, M., Hennessy, L., Herman , P., Hofwijks, N., Horien, C., Ionescu, T., Jones, J., Kaesser, J., Kim, E., Lambers, H., Lazari, A., Lee, S., Lillywhite, A., Liu, Y., López-Castro, A., López-Gil , X., Ma, Z., MacNicol, E., Madularu, D., Mandino, F., Marciano, S., McAuslan, M., McCunn, P., McIntosh, A., Meng, X., Meyer-Baese, L., Missault, S., Moro, F., Naessens, D., Nava-Gomez, L., Nonaka, H., Ortiz, J., Paasonen, J., Pais-Roldán, P., https://orcid.org/0000-0002-9381-3048, Peeters, L., Pereira, M., Perez, P., Pompilus, M., Prior, M., Rakhmatullin, R., Reimann, H., Reinwald, J., Triana Del Rio, R., Rivera-Olvera, A., Ruiz-Pérez, D., Russo, G., Rutten, T., Ryoke, R., Sack, M., Salvan, P., Sanganahalli, B., Schroeter, A., Seewoo , B., Selingue, E., Seuwen, A., Shi, B., Sirmpilatze, N., Smith, J., Smith, C., Sobczak, F., Stenroos, P., Straathof, M., Strobelt, S., Sumiyoshi, A., Takahashi, K., Torres-García, M., Tudela, R., van den Berg, M., van der Marel, K., van Hout, A., Vertullo, R., Vidal, B., Vrooman, R., Wang, X., Wank, I., Watson, D., Yin, T., Zhang, Y., Zurbruegg, S., Achard, S., Alcauter, S., Auer, D., Barbier, E., Baudewig, J., Beckmann, C., Beckmann, N., Becq, G., Blezer, E., Bolbos, R., Boretius, S., Bouvard, S., Budinger, E., Buxbaum, J., Cash, D., Chapman, V., Chuang, K., Ciobanu, L., Coolen, B., Dalley, J., Dhenain, M., Dijkhuizen, R., Esteban, O., Faber, C., Febo, M., Feindel, K., Forloni, G., Fouquet, J., Garza-Villarreal, E., Gass, N., Glennon, J., Gozzi, A., Gröhn, O., Harkin, A., Heerschap, A., Helluy, X., Herfert , K., Heuser, A., Homberg, J., Houwing, D., Hyder, F., Ielacqua, G., Jelescu, I., Johansen-Berg, H., Kaneko, G., Kawashima, R., Keilholz, S., Keliris, G., Kelly, C., Kerskens, C., Khokhar, J., Kind, P., Langlois, J., Lerch, J., López-Hidalgo, M., Manahan-Vaughan, D., Marchand, F., Mars, R., Marsella, G., Micotti , E., Muñoz-Moreno , E., Near, J., Niendorf, T., Otte, W., Pan , W., Prado-Alcalá, R., Quirarte, G., Rodger , J., Rosenow, T., Sampaio-Baptista, C., Sartorius, A., Sawiak, S., Scheenen, T., Shemesh, Shih, Y., Shmuel, A., https://orcid.org/0000-0003-3028-6639, Soria, G., Stoop, R., https://orcid.org/0000-0002-3532-1512, Thompson, G., Till, S., Todd, N., Van Der Linden, A., van der Toorn, A., van Tilborg, G., Vanhove, C., Veltien, A., Verhoye, M., Wachsmuth, L., Weber-Fahr, W., Wenk , P., Yu, X., Zerbi , V., Zhang , N., Zhang, B., Zimmer, L., Devenyi, G., Chakravarty, M., and Hess, A.

Subjects
General Neuroscience, Medizin
Abstract

Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. in press

Published
2023

3. Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease

Author

Kara, Firat, Belloy, Michael E., Voncken, Rick, Sarwari, Zahra, Garima, Yadav, Anckaerts, C., Linden, Annemie Van der, Verhoye, Marleen, Jacobs, J., Kara, Firat, Belloy, Michael E., Voncken, Rick, Sarwari, Zahra, Garima, Yadav, Anckaerts, C., Linden, Annemie Van der, Verhoye, Marleen, and Jacobs, J.

Abstract

Contains fulltext : 242956.pdf (Publisher’s version ) (Closed access)

Published
2021

4. Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Author

Grandjean, J., Canella, C., Anckaerts, C., Ayranci, G., Bougacha, S., Bienert, T., Buehlmann, D., Coletta, L., Gallino, D., Gass, N., Garin, C.M., Nadkarni, N.A., Hubner, N.S., Karatas, M., Komaki, Y., Kreitz, S., Mandino, F., Mechling, A.E., Sato, C., Sauer, K., Shah, D., Strobelt, S., Takata, N., Wank, I., Wu, T., Yahata, N., Yeow, L.Y., Yee, Y., Aoki, I., Chakravarty, M.M., Chang, W.T., Dhenain, M., Elverfeldt, D. von, Harsan, L.A., Hess, A., Jiang, T., Keliris, G.A., Lerch, J.P., Meyer-Lindenberg, A., Okano, H., Rudin, M., Sartorius, A., Linden, A. van der, Verhoye, M., Weber-Fahr, W., Wenderoth, N., Zerbi, V., Gozzi, A., Grandjean, J., Canella, C., Anckaerts, C., Ayranci, G., Bougacha, S., Bienert, T., Buehlmann, D., Coletta, L., Gallino, D., Gass, N., Garin, C.M., Nadkarni, N.A., Hubner, N.S., Karatas, M., Komaki, Y., Kreitz, S., Mandino, F., Mechling, A.E., Sato, C., Sauer, K., Shah, D., Strobelt, S., Takata, N., Wank, I., Wu, T., Yahata, N., Yeow, L.Y., Yee, Y., Aoki, I., Chakravarty, M.M., Chang, W.T., Dhenain, M., Elverfeldt, D. von, Harsan, L.A., Hess, A., Jiang, T., Keliris, G.A., Lerch, J.P., Meyer-Lindenberg, A., Okano, H., Rudin, M., Sartorius, A., Linden, A. van der, Verhoye, M., Weber-Fahr, W., Wenderoth, N., Zerbi, V., and Gozzi, A.

Abstract

Contains fulltext : 219632.pdf (publisher's version ) (Open Access), Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

Published
2020

5. A consensus protocol for functional connectivity analysis in the rat brain.

Author

Grandjean J, Desrosiers-Gregoire G, Anckaerts C, Angeles-Valdez D, Ayad F, Barrière DA, Blockx I, Bortel A, Broadwater M, Cardoso BM, Célestine M, Chavez-Negrete JE, Choi S, Christiaen E, Clavijo P, Colon-Perez L, Cramer S, Daniele T, Dempsey E, Diao Y, Doelemeyer A, Dopfel D, Dvořáková L, Falfán-Melgoza C, Fernandes FF, Fowler CF, Fuentes-Ibañez A, Garin CM, Gelderman E, Golden CEM, Guo CCG, Henckens MJAG, Hennessy LA, Herman P, Hofwijks N, Horien C, Ionescu TM, Jones J, Kaesser J, Kim E, Lambers H, Lazari A, Lee SH, Lillywhite A, Liu Y, Liu YY, López-Castro A, López-Gil X, Ma Z, MacNicol E, Madularu D, Mandino F, Marciano S, McAuslan MJ, McCunn P, McIntosh A, Meng X, Meyer-Baese L, Missault S, Moro F, Naessens DMP, Nava-Gomez LJ, Nonaka H, Ortiz JJ, Paasonen J, Peeters LM, Pereira M, Perez PD, Pompilus M, Prior M, Rakhmatullin R, Reimann HM, Reinwald J, Del Rio RT, Rivera-Olvera A, Ruiz-Pérez D, Russo G, Rutten TJ, Ryoke R, Sack M, Salvan P, Sanganahalli BG, Schroeter A, Seewoo BJ, Selingue E, Seuwen A, Shi B, Sirmpilatze N, Smith JAB, Smith C, Sobczak F, Stenroos PJ, Straathof M, Strobelt S, Sumiyoshi A, Takahashi K, Torres-García ME, Tudela R, van den Berg M, van der Marel K, van Hout ATB, Vertullo R, Vidal B, Vrooman RM, Wang VX, Wank I, Watson DJG, Yin T, Zhang Y, Zurbruegg S, Achard S, Alcauter S, Auer DP, Barbier EL, Baudewig J, Beckmann CF, Beckmann N, Becq GJPC, Blezer ELA, Bolbos R, Boretius S, Bouvard S, Budinger E, Buxbaum JD, Cash D, Chapman V, Chuang KH, Ciobanu L, Coolen BF, Dalley JW, Dhenain M, Dijkhuizen RM, Esteban O, Faber C, Febo M, Feindel KW, Forloni G, Fouquet J, Garza-Villarreal EA, Gass N, Glennon JC, Gozzi A, Gröhn O, Harkin A, Heerschap A, Helluy X, Herfert K, Heuser A, Homberg JR, Houwing DJ, Hyder F, Ielacqua GD, Jelescu IO, Johansen-Berg H, Kaneko G, Kawashima R, Keilholz SD, Keliris GA, Kelly C, Kerskens C, Khokhar JY, Kind PC, Langlois JB, Lerch JP, López-Hidalgo MA, Manahan-Vaughan D, Marchand F, Mars RB, Marsella G, Micotti E, Muñoz-Moreno E, Near J, Niendorf T, Otte WM, Pais-Roldán P, Pan WJ, Prado-Alcalá RA, Quirarte GL, Rodger J, Rosenow T, Sampaio-Baptista C, Sartorius A, Sawiak SJ, Scheenen TWJ, Shemesh N, Shih YI, Shmuel A, Soria G, Stoop R, Thompson GJ, Till SM, Todd N, Van Der Linden A, van der Toorn A, van Tilborg GAF, Vanhove C, Veltien A, Verhoye M, Wachsmuth L, Weber-Fahr W, Wenk P, Yu X, Zerbi V, Zhang N, Zhang BB, Zimmer L, Devenyi GA, Chakravarty MM, and Hess A

Subjects
Rats, Animals, Consensus, Neuroimaging, Magnetic Resonance Imaging methods, Brain, Brain Mapping methods
Abstract

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2023
Full Text
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6. Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease.

Author

Kara F, Belloy ME, Voncken R, Sarwari Z, Garima Y, Anckaerts C, Langbeen A, Leysen V, Shah D, Jacobs J, Hamaide J, Bols P, Van Audekerke J, Daans J, Guglielmetti C, Kantarci K, Prevot V, Roßner S, Ponsaerts P, Van der Linden A, and Verhoye M

Subjects
Alzheimer Disease etiology, Alzheimer Disease genetics, Animals, Biomarkers, Disease Models, Animal, Genotype, Magnetic Resonance Imaging, Mice, Inbred C57BL, Mice, Transgenic, Placebos, Risk Factors, Time Factors, White Matter diagnostic imaging, Mice, Alzheimer Disease diagnostic imaging, Alzheimer Disease psychology, Brain Chemistry, Executive Function, Ovariectomy adverse effects, White Matter metabolism, White Matter physiopathology
Abstract

Premenopausal bilateral ovariectomy is considered to be one of the risk factors of Alzheimer's disease (AD). However, the underlying mechanisms remain unclear. Here, we aimed to investigate long-term neurological consequences of ovariectomy in a rodent AD model, TG2576 (TG), and wild-type mice (WT) that underwent an ovariectomy or sham-operation, using in vivo MRI biomarkers. An increase in osmoregulation and energy metabolism biomarkers in the hypothalamus, a decrease in white matter integrity, and a decrease in the resting-state functional connectivity was observed in ovariectomized TG mice compared to sham-operated TG mice. In addition, we observed an increase in functional connectivity in ovariectomized WT mice compared to sham-operated WT mice. Furthermore, genotype (TG vs. WT) effects on imaging markers and GFAP immunoreactivity levels were observed, but there was no effect of interaction (Genotype × Surgery) on amyloid-beta-and GFAP immunoreactivity levels. Taken together, our results indicated that both genotype and ovariectomy alters imaging biomarkers associated with AD., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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7. Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis.

Author

Grandjean J, Canella C, Anckaerts C, Ayrancı G, Bougacha S, Bienert T, Buehlmann D, Coletta L, Gallino D, Gass N, Garin CM, Nadkarni NA, Hübner NS, Karatas M, Komaki Y, Kreitz S, Mandino F, Mechling AE, Sato C, Sauer K, Shah D, Strobelt S, Takata N, Wank I, Wu T, Yahata N, Yeow LY, Yee Y, Aoki I, Chakravarty MM, Chang WT, Dhenain M, von Elverfeldt D, Harsan LA, Hess A, Jiang T, Keliris GA, Lerch JP, Meyer-Lindenberg A, Okano H, Rudin M, Sartorius A, Van der Linden A, Verhoye M, Weber-Fahr W, Wenderoth N, Zerbi V, and Gozzi A

Subjects
Animals, Brain diagnostic imaging, Connectome standards, Female, Image Processing, Computer-Assisted standards, Magnetic Resonance Imaging standards, Male, Mice, Mice, Inbred C57BL, Nerve Net diagnostic imaging, Reproducibility of Results, Brain physiology, Connectome methods, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, Nerve Net physiology
Abstract

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2020
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8. Hypersynchronicity in the default mode-like network in a neurodevelopmental animal model with relevance for schizophrenia.

Author

Missault S, Anckaerts C, Ahmadoun S, Blockx I, Barbier M, Bielen K, Shah D, Kumar-Singh S, De Vos WH, Van der Linden A, Dedeurwaerdere S, and Verhoye M

Subjects
Animals, Behavior, Animal physiology, Brain drug effects, Disease Models, Animal, Female, Immunity, Active physiology, Magnetic Resonance Imaging methods, Male, Motor Activity drug effects, Poly I-C pharmacology, Pregnancy, Prenatal Exposure Delayed Effects metabolism, Prenatal Exposure Delayed Effects physiopathology, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate metabolism, Rest, Schizophrenia metabolism, Weight Gain, Weight Loss, Immunity, Active immunology, Schizophrenia etiology, Schizophrenia immunology
Abstract

Background: Immune activation during pregnancy is an important risk factor for schizophrenia. Brain dysconnectivity and NMDA receptor (NMDAR) hypofunction have been postulated to be central to schizophrenia pathophysiology. The aim of this study was to investigate resting-state functional connectivity (resting-state functional MRI-rsfMRI), microstructure (diffusion tension imaging-DTI) and response to NMDAR antagonist (pharmacological fMRI-phMRI) using multimodal MRI in offspring of pregnant dams exposed to immune challenge (maternal immune activation-MIA model), and determine whether these neuroimaging readouts correlate with schizophrenia-related behaviour., Methods: Pregnant rats were injected with Poly I:C or saline on gestational day 15. The maternal weight response was assessed. Since previous research has shown behavioural deficits can differ between MIA offspring dependent on the maternal response to immune stimulus, offspring were divided into three groups: controls (saline, n = 11), offspring of dams that gained weight (Poly I:C WG, n = 12) and offspring of dams that lost weight post-MIA (Poly I:C WL, n = 16). Male adult offspring were subjected to rsfMRI, DTI, phMRI with NMDAR antagonist, behavioural testing and histological assessment., Results: Poly I:C WL offspring exhibited increased functional connectivity in default mode-like network (DMN). Poly I:C WG offspring showed the most pronounced attenuation in NMDAR antagonist response versus controls. DTI revealed no differences in Poly I:C offspring versus controls. Poly I:C offspring exhibited anxiety., Conclusions: MIA offspring displayed a differential pathophysiology depending on the maternal response to immune challenge. While Poly I:C WL offspring displayed hypersynchronicity in the DMN, altered NMDAR antagonist response was most pronounced in Poly I:C WG offspring., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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9. Early functional connectivity deficits and progressive microstructural alterations in the TgF344-AD rat model of Alzheimer's Disease: A longitudinal MRI study.

Author

Anckaerts C, Blockx I, Summer P, Michael J, Hamaide J, Kreutzer C, Boutin H, Couillard-Després S, Verhoye M, and Van der Linden A

Subjects
Alzheimer Disease diagnostic imaging, Amyloid beta-Protein Precursor genetics, Animals, Brain diagnostic imaging, Brain Mapping, Disease Models, Animal, Female, Longitudinal Studies, Magnetic Resonance Imaging, Neural Pathways diagnostic imaging, Neural Pathways pathology, Neural Pathways physiopathology, Presenilin-1 genetics, Rats, Inbred F344, Rats, Transgenic, Alzheimer Disease pathology, Alzheimer Disease physiopathology, Brain pathology, Brain physiopathology
Abstract

The development and characterization of new improved animal models is pivotal in Alzheimer's Disease (AD) research, since valid models enable the identification of early pathological processes, which are often not accessible in patients, as well as subsequent target discovery and evaluation. The TgF344-AD rat model of AD, bearing mutant human amyloid precursor protein (APPswe) and Presenilin 1 (PSEN1ΔE9) genes, has been described to manifest the full spectrum of AD pathology similar to human AD, i.e. progressive cerebral amyloidosis, tauopathy, neuronal loss and age-dependent cognitive decline. Here, AD-related pathology in female TgF344-AD rats was examined longitudinally between 6 and 18 months by means of complementary translational MRI techniques: resting state functional MRI (rsfMRI) to evaluate functional connectivity (FC) and diffusion tensor imaging (DTI) to assess the microstructural integrity. Additionally, an evaluation of macroscopic changes (3D anatomical MRI) and an image-guided validation of ex vivo pathology were performed. We identified slightly decreased FC at 6 months followed by severe and widespread hypoconnectivity at 10 months of age as the earliest detectable pathological MRI hallmark. This initial effect was followed by age-dependent progressive microstructural deficits in parallel with age-dependent ex vivo AD pathology, without signs of macroscopic alterations such as hippocampal atrophy. This longitudinal MRI study in the TgF344-AD rat model of AD revealed early rsfMRI and DTI abnormalities as seen in human AD patients. The characterization of AD pathology in this rat model using non-invasive MRI techniques further highlights the translational value of this model, as well as its use for potential treatment evaluation., (Copyright © 2018. Published by Elsevier Inc.)

Published
2019
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10. Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury.

Author

Missault S, Anckaerts C, Blockx I, Deleye S, Van Dam D, Barriche N, De Pauw G, Aertgeerts S, Valkenburg F, De Deyn PP, Verhaeghe J, Wyffels L, Van der Linden A, Staelens S, Verhoye M, and Dedeurwaerdere S

Subjects
Animals, Diffusion Tensor Imaging methods, Male, Positron-Emission Tomography methods, Prognosis, Rats, Rats, Sprague-Dawley, Brain Injuries, Traumatic pathology, Encephalitis pathology, Neuroimaging methods, Recovery of Function
Abstract

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to controlled cortical impact (CCI) injury, sham surgery, or skin incision (naïve). CCI-injured (n = 18) and sham-operated rats (n = 6) underwent positron emission tomography (PET) imaging with the translocator protein 18 kDa (TSPO) radioligand [ 18 F]PBR111 and diffusion tensor imaging (DTI) in the subacute phase (≤3 weeks post-injury) to quantify inflammation and microstructural alterations. CCI-injured, sham-operated, and naïve rats (n = 8) underwent behavioral testing in the chronic phase (5.5-10 months post-injury): open field and sucrose preference tests, two one-week video-electroencephalogram (vEEG) monitoring periods, pentylenetetrazole (PTZ) seizure susceptibility tests, and a Morris water maze (MWM) test. In vivo imaging revealed pronounced neuroinflammation, decreased fractional anisotropy, and increased diffusivity in perilesional cortex and ipsilesional hippocampus of CCI-injured rats. Behavioral analysis revealed disinhibition, anhedonia, increased seizure susceptibility, and impaired learning in CCI-injured rats. Subacute TSPO expression and changes in DTI metrics significantly correlated with several chronic deficits (Pearson's |r| = 0.50-0.90). Certain specific PET and DTI parameters had good sensitivity and specificity (area under the receiver operator characteristic [ROC] curve = 0.85-1.00) to distinguish between TBI animals with and without particular behavioral deficits. Depending on the investigated behavioral deficit, PET or DTI data alone, or the combination, could very well predict the variability in functional outcome data (adjusted R 2  = 0.54-1.00). Taken together, both TSPO PET and DTI seem promising prognostic biomarkers to predict different chronic TBI sequelae.

Published
2019
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11. Image-guided phenotyping of ovariectomized mice: altered functional connectivity, cognition, myelination, and dopaminergic functionality.

Author

Anckaerts C, van Gastel J, Leysen V, Hinz R, Azmi A, Simoens P, Shah D, Kara F, Langbeen A, Bols P, Laloux C, Prevot V, Verhoye M, Maudsley S, and Van der Linden A

Subjects
Animals, Brain diagnostic imaging, Brain metabolism, Cell Cycle Proteins, Cellular Senescence genetics, Cognitive Dysfunction genetics, Cognitive Dysfunction metabolism, Female, Gene Expression, Hypothalamo-Hypophyseal System, Magnetic Resonance Imaging, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Inbred C57BL, Nuclear Receptor Subfamily 4, Group A, Member 2 genetics, Nuclear Receptor Subfamily 4, Group A, Member 2 metabolism, Pituitary-Adrenal System, Receptors, Dopamine D3 genetics, Receptors, Dopamine D3 metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Brain pathology, Brain physiopathology, Cognitive Dysfunction etiology, Ovariectomy adverse effects
Abstract

A large proportion of the population suffers from endocrine disruption, e.g., menopausal women, which might result in accelerated aging and a higher risk for developing cognitive disorders. Therefore, it is crucial to fully understand the impact of such disruptions on the brain to identify potential therapeutic strategies. Here, we show using resting-state functional magnetic resonance imaging that ovariectomy and consequent hypothalamus-pituitary-gonadal disruption result in the selective dysconnectivity of 2 discrete brain regions in mice. This effect coincided with cognitive deficits and an underlying pathological molecular phenotype involving an imbalance of neurodevelopmental/neurodegenerative signaling. Furthermore, this quantitative mass spectrometry proteomics-based analysis of molecular signaling patterns further identified a strong involvement of altered dopaminergic functionality (e.g., DAT and predicted upstream regulators DRD3, NR4A2), reproductive signaling (e.g., Srd5a2), rotatin expression (rttn), cellular aging (e.g., Rxfp3, Git2), myelination, and axogenesis (e.g., Nefl, Mag). With this, we have provided an improved understanding of the impact of hypothalamus-pituitary-gonadal dysfunction and highlighted the potential of using a highly translational magnetic resonance imaging technique for monitoring these effects on the brain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
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12. Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition.

Author

Shah D, Praet J, Latif Hernandez A, Höfling C, Anckaerts C, Bard F, Morawski M, Detrez JR, Prinsen E, Villa A, De Vos WH, Maggi A, D'Hooge R, Balschun D, Rossner S, Verhoye M, and Van der Linden A

Subjects
Alzheimer Disease diagnostic imaging, Animals, Autoantibodies pharmacology, Brain diagnostic imaging, Brain Mapping, Cerebrovascular Circulation physiology, Cortical Synchronization physiology, Disease Models, Animal, Disease Progression, Longitudinal Studies, Magnetic Resonance Imaging, Mice, Transgenic, Neural Pathways diagnostic imaging, Neural Pathways physiopathology, Neuroprotective Agents pharmacology, Oxygen blood, Plaque, Amyloid diagnostic imaging, Plaque, Amyloid physiopathology, Plaque, Amyloid prevention & control, Prodromal Symptoms, Rest, Alzheimer Disease drug therapy, Alzheimer Disease physiopathology, Amyloid beta-Peptides antagonists & inhibitors, Amyloid beta-Peptides metabolism, Brain drug effects, Brain physiopathology
Abstract

Introduction: In Alzheimer's disease (AD), pathologic amyloid-beta (Aβ) is synaptotoxic and impairs neuronal function at the microscale, influencing brain networks at the macroscale before Aβ deposition. The latter can be detected noninvasively, in vivo, using resting-state functional MRI (rsfMRI), a technique used to assess brain functional connectivity (FC)., Methods: RsfMRI was performed longitudinally in TG2576 and PDAPP mice, starting before Aβ deposition to determine the earliest FC changes. Additionally, the role of pathologic Aβ on early FC alterations was investigated by treating TG2576 mice with the 3D6 anti-Aβ-antibody., Results: Both transgenic models showed hypersynchronized FC before Aβ deposition and hyposynchronized FC at later stages. Early anti-Aβ treatment in TG2576 mice prevented hypersynchronous FC and the associated synaptic impairments and excitatory/inhibitory disbalances., Discussion: Hypersynchrony of FC may be used as a new noninvasive read out of early AD and can be recovered by anti-Aβ treatment, encouraging preventive treatment strategies in familial AD., (Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Published
2016
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