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24-01-2025 | Anorexia Nervosa | Neurology and Preclinical Neurological Studies - Review Article

The brainstem reticular formation pivots abnormal neural transmission in the course of Anorexia Nervosa

Authors: Gloria Lazzeri, Carla L. Busceti, Alessandra Polzella, Alessandro Frati, Stefano Puglisi-Allegra, Francesco Fornai

Published in: Journal of Neural Transmission

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Abstract

Anorexia nervosa (AN) represents an eating disorder, which features the highest rate of mortality among all psychiatric disorders. The disease prevalence is increasing steadily, and an effective cure is missing. The neurobiology of the disease is largely unknown, and only a few studies were designed to disclose specific brain areas, where altered neural transmission may occur. In AN behavioral alterations surpassing altered feeding are present, which often involve archaic behaviors finalized to the survival of the species. In fact, alterations of sleep and reward-driven behavior accompany the eating disorder, where a disruption of peripheral and central circadian rhythms occurs along with effortful behaviors, aberrant learning and mild cognitive impairment. Abnormal behavior often co-exists with a number of metabolic alterations in peripheral organs. The present article wishes to analyze the potential role of altered brain circuitry within the brainstem reticular formation during AN. In fact, this brain area contains neuronal nuclei and pathways, which are pivotal in connecting eating pattern with archaic behaviorsand autonomic activity within peripheral organs. A number of reticular nuclei releasing catecholamine and non-catecholamine neurotransmittersare evidenced in relationship with altered behavioral states and vegetative control to produce this psycho-metabolic disorder. The relevance of the reticular formation in sustaining the disorder is discussed in the light of developing effective therapeutic strategies.
Literature
go back to reference Abdolizadeh A, Hosseini Kupaei M, Kambari Y, Amaev A, Korann V, Torres-Carmona E, Song J, Ueno F, Koizumi MT, Nakajima S, Agarwal SM, Gerretsen P, Graff-Guerrero A (2024) The effect ofsecond-generation antipsychotics on anxiety/depression in patients with schizophrenia: a systematic review and meta-analysis. Schizophr Res 270:11–36. https://doi.org/10.1016/j.schres.2024.05.020CrossRefPubMed Abdolizadeh A, Hosseini Kupaei M, Kambari Y, Amaev A, Korann V, Torres-Carmona E, Song J, Ueno F, Koizumi MT, Nakajima S, Agarwal SM, Gerretsen P, Graff-Guerrero A (2024) The effect ofsecond-generation antipsychotics on anxiety/depression in patients with schizophrenia: a systematic review and meta-analysis. Schizophr Res 270:11–36. https://​doi.​org/​10.​1016/​j.​schres.​2024.​05.​020CrossRefPubMed
go back to reference Dominique M, Legrand R, Galmiche M, Azhar S, Deroissart C, Guérin C, do Rego JL, Leon F, Nobis S, Lambert G, Lucas N, Déchelotte P (2019) Changes in microbiota and bacterial protein Caseinolytic Peptidase B during Food Restriction in mice:relevance for the Onset and Perpetuation of Anorexia Nervosa. Nutrients 11:2514. https://doi.org/10.3390/nu11102514CrossRefPubMedPubMedCentral Dominique M, Legrand R, Galmiche M, Azhar S, Deroissart C, Guérin C, do Rego JL, Leon F, Nobis S, Lambert G, Lucas N, Déchelotte P (2019) Changes in microbiota and bacterial protein Caseinolytic Peptidase B during Food Restriction in mice:relevance for the Onset and Perpetuation of Anorexia Nervosa. Nutrients 11:2514. https://​doi.​org/​10.​3390/​nu11102514CrossRefPubMedPubMedCentral
go back to reference Ellison GD (1975) Behavior and the balance between norepinephrine and serotonin. Acta Neurobiol Exp (Wars) 35:499–515PubMed Ellison GD (1975) Behavior and the balance between norepinephrine and serotonin. Acta Neurobiol Exp (Wars) 35:499–515PubMed
go back to reference Evans R, Kimura H, Nakashima M, Ishikawa T, Yukitake H, Suzuki M, Hazel J, Faessel H, Wu J, Hang Y, Alexander R, Rosen L, Hartman DS, Ratti E (2023) Orexin 2receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals. J Sleep Res 32:e13878. https://doi.org/10.1111/jsr.13878CrossRefPubMed Evans R, Kimura H, Nakashima M, Ishikawa T, Yukitake H, Suzuki M, Hazel J, Faessel H, Wu J, Hang Y, Alexander R, Rosen L, Hartman DS, Ratti E (2023) Orexin 2receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals. J Sleep Res 32:e13878. https://​doi.​org/​10.​1111/​jsr.​13878CrossRefPubMed
go back to reference Kilpatrick LA, Gupta A, Meriwether D, Mahurkar-Joshi S, Li VW, Sohn J, Reist J, Labus JS, Dong T, Jacobs JP, Naliboff BD, Chang L, Mayer EA (2024) Differential brainstem connectivity according to sex and menopausal status in healthy men and women. Res Sq [Preprint]. 12:rs.3.rs-4875269 Kilpatrick LA, Gupta A, Meriwether D, Mahurkar-Joshi S, Li VW, Sohn J, Reist J, Labus JS, Dong T, Jacobs JP, Naliboff BD, Chang L, Mayer EA (2024) Differential brainstem connectivity according to sex and menopausal status in healthy men and women. Res Sq [Preprint]. 12:rs.3.rs-4875269
go back to reference Lambert PD, Couceyro PR, McGirr KM, Dall Vechia SE, Smith Y, Kuhar MJ (1998) CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse 29:293–298 Lambert PD, Couceyro PR, McGirr KM, Dall Vechia SE, Smith Y, Kuhar MJ (1998) CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse 29:293–298
go back to reference Maxwell ND, Smiley CE, Sadek AT, Loyo-Rosado FZ, Giles DC, Macht VA, Woodruff JL, Taylor DL, Glass VM, Wilson SP, Reagan LP, Fadel JR, Grillo CA (2024) Leptin activation of dorsal raphe neurons inhibits feeding behavior. Diabetes 21:db240207. https://doi.org/10.2337/db24-0207CrossRef Maxwell ND, Smiley CE, Sadek AT, Loyo-Rosado FZ, Giles DC, Macht VA, Woodruff JL, Taylor DL, Glass VM, Wilson SP, Reagan LP, Fadel JR, Grillo CA (2024) Leptin activation of dorsal raphe neurons inhibits feeding behavior. Diabetes 21:db240207. https://​doi.​org/​10.​2337/​db24-0207CrossRef
go back to reference Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. ElectroencephalogrClinNeurophysiol 1:455–473 Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. ElectroencephalogrClinNeurophysiol 1:455–473
go back to reference Nakamori H, Naitou K, Horii Y, Shimaoka H, Horii K, Sakai H, Yamada A, Furue H, Shiina T, Shimizu Y (2019) Roles of the noradrenergic nucleus locus coeruleus and dopaminergic nucleus A11 region as supraspinal defecation centers in rats. Am J PhysiolGastrointest Liver Physiol 317:G545–G555. https://doi.org/10.1152/ajpgi.00062.2019CrossRef Nakamori H, Naitou K, Horii Y, Shimaoka H, Horii K, Sakai H, Yamada A, Furue H, Shiina T, Shimizu Y (2019) Roles of the noradrenergic nucleus locus coeruleus and dopaminergic nucleus A11 region as supraspinal defecation centers in rats. Am J PhysiolGastrointest Liver Physiol 317:G545–G555. https://​doi.​org/​10.​1152/​ajpgi.​00062.​2019CrossRef
go back to reference Nimmons D, Bazo-Alvarez JC, Avgerinou C, Hayes J, Osborn D, Cooper C, Petersen I, Walters K (2024) Exploring the co-occurrence of depression, anxiety and insomnia symptoms, diagnoses and treatments in primary care: observational study using UK primary care data. B J Psych Open 10:e76. https://doi.org/10.1192/bjo.2024.20CrossRef Nimmons D, Bazo-Alvarez JC, Avgerinou C, Hayes J, Osborn D, Cooper C, Petersen I, Walters K (2024) Exploring the co-occurrence of depression, anxiety and insomnia symptoms, diagnoses and treatments in primary care: observational study using UK primary care data. B J Psych Open 10:e76. https://​doi.​org/​10.​1192/​bjo.​2024.​20CrossRef
go back to reference Nobis S, Achamrah N, Goichon A, L’Huillier C, Morin A, Guérin C, Chan P, do Rego JL, do, Rego JC, Vaudry D, Déchelotte P, Belmonte L, Coëffier M (2018b) Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia-Induced Malnutrition in Mice. Proteomics 18: e1700395. https://doi.org/10.1002/pmic.201700395 Nobis S, Achamrah N, Goichon A, L’Huillier C, Morin A, Guérin C, Chan P, do Rego JL, do, Rego JC, Vaudry D, Déchelotte P, Belmonte L, Coëffier M (2018b) Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia-Induced Malnutrition in Mice. Proteomics 18: e1700395. https://​doi.​org/​10.​1002/​pmic.​201700395
go back to reference Nobis S, Morin A, Achamrah N, Belmonte L, Legrand R, Chan P, do Rego JL, Vaudry D, Gourcerol G, Déchelotte P, Goichon A, Coëffier M (2018c) Delayed gastric emptying and altered antrum protein metabolism during activity-based anorexia. NeurogastroenterolMotil 30: e13305. https://doi.org/10.1111/nmo.13305 Nobis S, Morin A, Achamrah N, Belmonte L, Legrand R, Chan P, do Rego JL, Vaudry D, Gourcerol G, Déchelotte P, Goichon A, Coëffier M (2018c) Delayed gastric emptying and altered antrum protein metabolism during activity-based anorexia. NeurogastroenterolMotil 30: e13305. https://​doi.​org/​10.​1111/​nmo.​13305
go back to reference Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic, San Diego Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic, San Diego
go back to reference Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press Inc, San Diego Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press Inc, San Diego
go back to reference Pristerà A, Lin W, Kaufmann AK, Brimblecombe KR, Threlfell S, Dodson PD, Magill PJ, Fernandes C, Cragg SJ, Ang SL (2015) Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. Proc Natl AcadSci USA 112:E4929–E4938. https://doi.org/10.1073/pnas.1503911112CrossRef Pristerà A, Lin W, Kaufmann AK, Brimblecombe KR, Threlfell S, Dodson PD, Magill PJ, Fernandes C, Cragg SJ, Ang SL (2015) Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. Proc Natl AcadSci USA 112:E4929–E4938. https://​doi.​org/​10.​1073/​pnas.​1503911112CrossRef
go back to reference Salaün C, Courvalet M, Rousseau L, Cailleux K, Breton J, Bôle-Feysot C, Guérin C, Huré M, Goichon A, do Rego JC, Déchelotte P, Ribet D, Achamrah N, Coëffier M (2024) Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut-microbiota composition during activity-based anorexia in mice. Biol Sex Differ 15:6. https://doi.org/10.1186/s13293-023-00576-xCrossRefPubMedPubMedCentral Salaün C, Courvalet M, Rousseau L, Cailleux K, Breton J, Bôle-Feysot C, Guérin C, Huré M, Goichon A, do Rego JC, Déchelotte P, Ribet D, Achamrah N, Coëffier M (2024) Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut-microbiota composition during activity-based anorexia in mice. Biol Sex Differ 15:6. https://​doi.​org/​10.​1186/​s13293-023-00576-xCrossRefPubMedPubMedCentral
go back to reference Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ, Masad I, Muniz JA, Grant SC, Gold MS, Cadet JL, Volkow ND (2016) Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS One 11: e0155457. https://doi.org/10.1371/journal.pone.0155457. Erratum in: PLoS One (2017) 12: e0172080.doi: 10.1371/journal.pone.0172080 Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ, Masad I, Muniz JA, Grant SC, Gold MS, Cadet JL, Volkow ND (2016) Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS One 11: e0155457. https://​doi.​org/​10.​1371/​journal.​pone.​0155457. Erratum in: PLoS One (2017) 12: e0172080.doi: 10.1371/journal.pone.0172080
Metadata
Title
The brainstem reticular formation pivots abnormal neural transmission in the course of Anorexia Nervosa
Authors
Gloria Lazzeri
Carla L. Busceti
Alessandra Polzella
Alessandro Frati
Stefano Puglisi-Allegra
Francesco Fornai
Publication date
24-01-2025
Publisher
Springer Vienna
Published in
Journal of Neural Transmission
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-025-02881-8

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