In utero exposure to selective serotonin re‐uptake inhibitor affects murine mandibular development

Boyce, M. A.; Durham, Emily L.; Kuo, Sharon; Taylor, Jane M; Kishinchand, Rajiv; LaRue, Amanda C.; Cray, James J.

doi:10.1111/ocr.12624

Cited by 2 publications

(5 citation statements)

References 40 publications

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“…Dynamic changes in brain and skull shape track on one another regardless of changes in biomechanical and physiological function [ 18 ]. These data correlate with published data indicating changes in skull form after exposure to SSRI [ 27 , 33 , 36 ].…”

Section: Discussionsupporting

confidence: 91%

“…This timepoint allowed for this assessment as the bone was developed enough to measure these changes in form. SSRIs have been found to specifically affect bone-related cells resulting in an overall decrease in bone in many cases [ 22 , 27 , 33 – 35 ]. This may also account for the increased endocast volume as bone may be thinner in SSRI exposed individuals (however we recorded no significant differences in bone volume between exposed and control skulls (p = 0.6049).…”

Section: Discussionmentioning

confidence: 99%

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Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model

Saluan,

Bauer,

Vyas

et al. 2024

PLoS ONE

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Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model

Saluan,

Bauer,

Vyas

et al. 2024

PLoS ONE

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“…Marine natural products are a proven source of emerging drugs, especially in the treatments of cancers and infectious diseases. − One emerging product that has enjoyed significant attention is manzamine-A (MA), a marine sponge-derived alkaloid that has presented as a promising control for malaria. ,− The utility of manzamine and its derived analogues in medicine is nascent, but it is proposed to include treatment for malaria, − herpes, ,− HIV, ,,− and cancer, ,,,,− ,, and this product demonstrates antibacterial, antifungal, and anti-inflammatory properties. ,,,,,,,− ,,− …”

mentioning

confidence: 99%

“…Our group has a keen interest in the mechanism by which established and emerging drug exposures might alter health of the mineralized tissues of the body, specifically bone. − Understanding these interactions is critical as bone loss diseases are on the rise, notably osteoporosis. , The Center for Disease Control (United States) reports the age-adjusted prevalence of osteoporosis has increased in the past decade from 9.5% in 2008 to 12.6% in 2018 . Our most recent work has focused on MA and how the cells responsible for bone development, maintenance, and remodeling, osteoblasts, are affected by its exposure .…”

mentioning

confidence: 99%

“…1−24 One emerging product that has enjoyed significant attention is manzamine-A (MA), a marine sponge-derived alkaloid that has presented as a promising control for malaria. 19,25−31 The utility of manzamine and its derived analogues in medicine is nascent, but it is proposed to include treatment for malaria, 25−32 herpes, 27,33−35 HIV, 27,30,36−41 and cancer, 6,10,13,35,[37][38][39]44,45 and this product demonstrates antibacterial, antifungal, and anti-inflammatory properties. 15,17,19,20,24,32,34,36−38,43,52−55 Manzamine alkaloids are isolated from Indo-Pacific sponges and represent a group of complex Beta-carboline alkaloids characterized by a unique nitrogen-containing polycyclic system.…”

mentioning

confidence: 99%

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Manzamine-A Alters In Vitro Calvarial Osteoclast Function

Maykovich,

Hardy,

Hamann

et al. 2024

J. Nat. Prod.

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Manzamine-A is a marine-derived alkaloid that has demonstrated antimalarial and antiproliferative properties and is an emerging drug lead compound as a possible intervention in certain cancers. This compound has been found to modulate SIX1 gene expression, a target that is critical for the proliferation and survival of cells via various developmental pathways. As yet, little research has focused on manzamine-A and how its use may affect tissue systems including bone. Here we hypothesized that manzamine-A, through its interaction with SIX1, would alter precursor cells that give rise to the bone cell responsible for remodeling: the osteoclast. We further hypothesized reduced effects in differentiated osteoclasts, as these cells are generally not mitotic. We interrogated the effects of manzamine-A on preosteoclasts and osteoclasts. qrtPCR, MTS cell viability, Caspase 3/7, and TRAP staining were used as a functional assay. Preosteoclasts show responsiveness to manzamine-A treatment exhibited by decreases in cell viability and an increase in apoptosis. Osteoclasts also proved to be affected by manzamine-A but only at higher concentrations where apoptosis was increased and activation was reduced. In summary, our presented results suggest manzamine-A may have significant effects on bone development and health through multiple cell targets, previously shown in the osteoblast cell lineage, the cell responsible for mineralized tissue formation, and here in the osteoclast, the cell responsible for the removal of mineralized tissue and renewal via precipitation of bone remodeling.

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In utero exposure to selective serotonin re‐uptake inhibitor affects murine mandibular development

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 2 publications

References 40 publications

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model

Manzamine-A Alters In Vitro Calvarial Osteoclast Function

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