المؤلفون: Pan, Shelei, Hale, Andrew T., Lemieux, Mackenzie E., Raval, Dhvanii K., Garton, Thomas P., Sadler, Brooke, Mahaney, Kelly B., Strahle, Jennifer M.

المصدر: Frontiers in Neurology ; volume 14 ; ISSN 1664-2295

الوصف: Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH.

الإتاحة: https://doi.org/10.3389/fneur.2023.1287559Test

المؤلفون: Li, Hao, Namburi, Praneeth, Olson, Jacob M., Borio, Matilde, Lemieux, Mackenzie E., Beyeler, Anna, Calhoon, Gwendolyn G., Hitora-Imamura, Natsuko, Coley, Austin A., Libster, Avraham, Bal, Aneesh, Jin, Xin, Wang, Huan, Jia, Caroline, Choudhury, Sourav R., Shi, Xi, Felix-Ortiz, Ada C., de la Fuente, Veronica, Barth, Vanessa P., King, Hunter O., Izadmehr, Ehsan M., Revanna, Jasmin S., Batra, Kanha, Fischer, Kyle B., Keyes, Laurel R., Padilla-Coreano, Nancy, Siciliano, Cody A., Mccullough, Kenneth M., Wichmann, Romy, Ressler, Kerry J., Fiete, Ila R., Zhang, Feng, Li, Yulong, Tye, Kay M.

المساهمون: Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Salk Institute for Biological Studies, Howard Hughes Medical Institute, JPB Foundation, Alfred P. Sloan Foundation, New York Stem Cell Foundation, Klingenstein Third Generation Foundation, Kavli Foundation, Dolby Family Ventures, Pioneer Fund, Uehara Memorial Foundation

المصدر: https://hal.science/hal-04062021Test ; 2023.

مصطلحات موضوعية: Protein expression, Protein function, Signal transduction, Whole cell patch clamp, Amygdala, Physiology, Reward, Basolateral Nuclear Complex, Calcium, Neurotensin, Neuropeptide, Glutamic acid, Adult, Animal cell, Animal experiment, Animal tissue, Article, Associative learning, Basolateral amygdala, Brain region, C57BL 6 mouse, Cell culture, Cohort analysis, Confocal microscopy, Controlled study, CRISPR-CAS9 system, Female, Human, In situ hybridization, In vivo study

الوصف: The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different basolateral amygdala (BLA) projections are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence specific information is routed to the BLA neurons with the appropriate downstream projections. Nor do we understand how to reconcile the subsecond timescales of synaptic plasticity8–11 with the longer timescales separating the predictive cues from their outcomes. Here, we demonstrate that neurotensin (NT) neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, while PVT-BLA projection-specific Nt gene knockout augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nt gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference to active behavioral strategies to reward and punishment predictive cues. Taken together, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviorally-relevant timescales.

العلاقة: hal-04062021; https://hal.science/hal-04062021Test; https://hal.science/hal-04062021/documentTest; https://hal.science/hal-04062021/file/MAGENDIE_Nature_2022_Li.pdfTest

الإتاحة: https://doi.org/10.1038/s41586-022-04964-yTest
https://hal.science/hal-04062021Test
https://hal.science/hal-04062021/documentTest
https://hal.science/hal-04062021/file/MAGENDIE_Nature_2022_Li.pdfTest

المؤلفون: Shelei Pan, Hale, Andrew T., Lemieux, Mackenzie E., Raval, Dhvanii K., Garton, Thomas P., Sadler, Brooke, Mahaney, Kelly B., Strahle, Jennifer M.

المصدر: Frontiers in Neurology; 2024, p1-27, 27p

مصطلحات موضوعية: IRON in the body, CEREBRAL ventricles, IRON overload, HYDROCEPHALUS, IRON

مستخلص: Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH. [ABSTRACT FROM AUTHOR]

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المؤلفون: Li, Hao, Namburi, Praneeth, Olson, Jacob M., Borio, Matilde, Lemieux, Mackenzie E., Beyeler, Anna, Calhoon, Gwendolyn G., Hitora-Imamura, Natsuko, Coley, Austin A., Libster, Avraham, Bal, Aneesh, Jin, Xin, Wang, Huan, Jia, Caroline, Choudhury, Sourav R., Shi, Xi, Felix-Ortiz, Ada C., de la Fuente, Verónica, Barth, Vanessa P., King, Hunter O., Izadmehr, Ehsan M., Revanna, Jasmin S., Batra, Kanha, Fischer, Kyle B., Keyes, Laurel R., Padilla-Coreano, Nancy, Siciliano, Cody A., McCullough, Kenneth M., Wichmann, Romy, Ressler, Kerry J., Fiete, Ila R., Zhang, Feng, Li, Yulong, Tye, Kay M.

المصدر: Nature ; volume 608, issue 7923, page 586-592 ; ISSN 0028-0836 1476-4687

مصطلحات موضوعية: Multidisciplinary

الإتاحة: https://doi.org/10.1038/s41586-022-04964-yTest
https://www.nature.com/articles/s41586-022-04964-y.pdfTest
https://www.nature.com/articles/s41586-022-04964-yTest