Browsing by Author "Asad, Iqra"

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    Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review
    (PLOS, 2022-03-31) Heng, Yi Yan; Asad, Iqra; Coleman, Bailey; Menard, Laura; Benki-Nugent, Sarah; Were, Faridah Hussein; Karr, Catherine J.; McHenry, Megan S.; Pediatrics, School of Medicine
    Background: The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. Methods: We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. Results: Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. Conclusions and potential impact: We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.
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    Role of Cx43 on the Bone Cell Generation, Function, and Survival
    (Mary Ann Liebert, 2023) Plotkin, Lilian I.; Asad, Iqra; Kritikos, Alex E.; Sanz, Natasha; Anatomy, Cell Biology and Physiology, School of Medicine
    The presence of gap junction intercellular communication structures in bone cells has been known since the early 1970s, further confirmed by Doty and Marotti at the structural level in the 1980-1990s. Work by Civitelli, Donahue, and others showed the expression of Cx43 at the mRNA and protein levels in all bone cell types: osteoclasts (bone resorbing cells), osteoblasts (bone forming cells), and osteocytes (mature osteoblasts embedded in the bone matrix that regulate the function of both osteoclasts and osteoblasts). While Cx45, Cx46, and Cx37 were also shown to be expressed in bone cells, most studies have focused on Cx43, the most abundant member of the connexin (Cx) family of proteins expressed in bone. The role of Cx43 has been shown to be related to the formation of gap junction intercellular channels, to unopposed hemichannels, and to channel independent functions of the molecule. Cx43 participates in the response of bone cells to pharmacological, hormonal, and mechanical stimuli, and it is involved in the skeletal phenotype with old age. Human and murine studies have shown that mutations of Cx43 lead to oculodentodigital dysplasia and craniometaphyseal dysplasia, both conditions associated with abnormalities in the skeleton. However, whereas substantial advances have been made on the skeletal role of Cx43, further research is needed to understand the basis for the effects of mutated Cx43 and potential ways to prevent the effects of these mutations on bone.
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    Sex hormone deficiency in male and female mice expressing the Alzheimer’s disease-associated risk-factor TREM2 R47H variant impacts the musculoskeletal system in a sex- and genotype-dependent manner
    (Oxford University Press, 2024-11-13) Pianeta, Roquelina; Deosthale, Padmini; Sanz, Natasha; Kohler, Rachel; Okpara, Chiebuka; Arnett, Matthew; Asad, Iqra; Rogers, Amber; Gerbig, Madison; Essex, Alyson; Liu, Ziyue; Wallace, Joseph M.; Plotkin, Lilian I.; Anatomy, Cell Biology and Physiology, School of Medicine
    The R47H variant of the triggering receptor expressed on myeloid cells 2 (TREM2) is a risk factor for Alzheimer's disease in humans and leads to lower bone mass accrual in female but not male 12-mo-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery was performed in 4-mo-old TREM2R47H/+ mice and WT male and female littermates (n = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype. Gonadectomy also leads to decreased BMD in males at all sites and in the whole body (total) and spine in female mice for both genotypes. Total and femur BMD was lower in gonadectomized male mice 6-wk post-surgery, independently of the genotype. On the other hand, BMD was only lower in ovariectomized WT but not TREM2R47H/+ mice in all sites measured at this time point. Bone formation and resorption marker levels were not affected by orchiectomy, whereas CTX was higher 3 wk after surgery and P1NP showed a tendency toward lower values at the 6-wk time point only in ovariectomized WT mice. Micro-CT analyses showed no differences resulting from gonadectomy in structural parameters in femoral cortical bone for either sex, but lower tissue mineral density in males of either genotype 6-wk post-surgery. Nevertheless, biomechanical properties were overall lower in gonadectomized males of either genotype, and only for WT ovariectomized mice. Distal femur cancellous bone structure was also affected by gonadectomy in a genotype- and sex-dependent manner, with genotype-independent changes in males, and only in WT female mice. Thus, expression of the TREM2 R47H variant minimally alters the impact of gonadectomy in the musculoskeletal system in males, whereas it partially ameliorates the consequences of ovariectomy in female mice.