The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice

Ahmed, Md. Mahiuddin; Wang, Athena Ching‐Jung; Elos, Mihret; Chial, Heidi J.; Sillau, Stefan; Solano, Daniel; Coughlan, Christina; Aghili, Leila; Anton, Paige; Markham, Neil E.; Adame, Vanesa; Gardiner, Katheleen; Boyd, Timothy; Potter, Huntington

doi:10.1016/j.nbd.2022.105694

Cited by 16 publications

(12 citation statements)

References 144 publications

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“…Another example is the innate immune system stimulating cytokine granulocytemacrophage colony-stimulating factor, which was shown to improve learning, memory, and interneuron and astrocyte brain pathology in both the Dp16 Down syndrome mouse model and in wild-type mice. 93 Several other comorbidities, especially sleep disorders, congenital heart defects (NCT05312177), and psychiatric disorders have also been postulated to affect cognition in the general population. However, a recent study reported that most health comorbidities, except for autism and epilepsy, are not directly associated with poorer cognitive outcomes in Down syndrome.…”

Section: Mu Lti Moda L Th Er a Py: Accou N Ti Ng For Th E Sy N Drom I...mentioning

confidence: 99%

State‐of‐the‐art therapy for Down syndrome

Lorenzón

Musoles-Lleó

Turrisi

et al. 2023

Develop Med Child Neuro

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Down syndrome is the most common chromosomal disorder, caused by a third copy of all or part of chromosome 21 (HSA21), and the most complex and prevalent genetic cause of intellectual disability. 1 It is a chronic, multifactorial disorder that affects brain development and function, impairing cognition and adaptive behaviour. 2 Moreover, Down syndrome co-occurs with autism and epilepsy and is considered a genetic form of Alzheimer disease. 3 In addition, individuals with Down syndrome have a high prevalence of endocrine disorders and obesity, leading to type 2 diabetes, insulin resistance, and neuroinflammation, 4 which, in turn, contribute to cognitive deficits.In the last decade, an important effort was made to better understand the pathogenetic mechanisms involved in Down

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Section: Mu Lti Moda L Th Er a Py: Accou N Ti Ng For Th E Sy N Drom I...mentioning

confidence: 99%

State‐of‐the‐art therapy for Down syndrome

Lorenzón

Musoles-Lleó

Turrisi

et al. 2023

Develop Med Child Neuro

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“…Intriguingly, an exaggerated microglia response occurs in the Ts65Dn brain in which BFCN degeneration has been induced compared with euploid controls, consistent with the hypothesis that trisomy of Hsa21 perturbs neuroinflammation (Hamlett et al, 2020b ). The use of anti-inflammatory or anti-oxidant treatments in the Ts65Dn model, including treatment with minocycline, vitamin E, resolvin E, granulocyte-macrophage colony-stimulating factor or anti-IL-17, rescues some of these neuroinflammatory phenotypes, neurodegeneration and cognition (Hunter et al, 2004a ; Lockrow et al, 2009 ; Rueda et al, 2018 ; Hamlett et al, 2020a ; Ahmed et al, 2022 ), showing the important role that neuroinflammation may have in AD-DS phenotypes.…”

Section: Pre-clinical Modeling Of Ad-ds: Mechanistic Insightsmentioning

confidence: 99%

Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches

2022

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There are an estimated 6 million people with Down syndrome (DS) worldwide. In developed countries, the vast majority of these individuals will develop Alzheimer's disease neuropathology characterized by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles within the brain, which leads to the early onset of dementia (AD-DS) and reduced life-expectancy. The mean age of onset of clinical dementia is ~55 years and by the age of 80, approaching 100% of individuals with DS will have a dementia diagnosis. DS is caused by trisomy of chromosome 21 (Hsa21) thus an additional copy of a gene(s) on the chromosome must cause the development of AD neuropathology and dementia. Indeed, triplication of the gene APP which encodes the amyloid precursor protein is sufficient and necessary for early onset AD (EOAD), both in people who have and do not have DS. However, triplication of other genes on Hsa21 leads to profound differences in neurodevelopment resulting in intellectual disability, elevated incidence of epilepsy and perturbations to the immune system. This different biology may impact on how AD neuropathology and dementia develops in people who have DS. Indeed, genes on Hsa21 other than APP when in three-copies can modulate AD-pathogenesis in mouse preclinical models. Understanding this biology better is critical to inform drug selection for AD prevention and therapy trials for people who have DS. Here we will review rodent preclinical models of AD-DS and how these can be used for both in vivo and ex vivo (cultured cells and organotypic slice cultures) studies to understand the mechanisms that contribute to the early development of AD in people who have DS and test the utility of treatments to prevent or delay the development of disease.

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“…It is comprised of immune organs, immune cells, and immune molecules. It prevents the invasion of pathogenic genes through the immune response and is essential in maintaining physiological balance [ 8 , 9 ]. Meanwhile, the intestine is the maximum digestive and absorptive organ, which also has vital defensive capabilities [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Major Royal Jelly Proteins on the Immune Response and Gut Microbiota Composition in Cyclophosphamide-Treated Mice

Wang

et al. 2023

Nutrients

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Increasing evidence suggests that royal jelly (RJ) has exceptional biological properties, and that major royal jelly proteins (MRJPs) are the key active factors in RJ. The objective of this study was to compare the difference in the protein content between RJ and MRJPs using non-labeled, quantitative proteomics technology, and to investigate the adjustment features and mechanisms of MRJPs on murine immune functions and the composition of intestinal flora in cyclophosphamide-treated mice. Results showed that, during the process of extracting MRJPs, the ratio of the protein types in the main protein and other proteins decreased significantly, except for MRJP1 and MRJP7, which demonstrated that an enriching effect of MRJP1 and MRJP7 was present during the extraction process. Cyclophosphamide-induced mice were orally administered MRJPs. Results showed that the middle-dose group, which received 0.25 g/(kg·bw) of royal jelly main protein, demonstrated a clear impact on the development of the spleen and liver, the quantity of peripheral blood leukocytes, immunoglobulin content, immune factor level, and the proliferation ability of spleen lymphocytes. A 16S rRNA high-throughput sequencing technology analysis showed that MRJPs could improve the component and richness of intestinal flora and raise the immunity of mice. The above-mentioned results indicated that the application of MRJPs is very likely to have an advantage effect on murine immune functions.

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The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice

Cited by 16 publications

References 144 publications

State‐of‐the‐art therapy for Down syndrome

State‐of‐the‐art therapy for Down syndrome

Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches

Effects of Major Royal Jelly Proteins on the Immune Response and Gut Microbiota Composition in Cyclophosphamide-Treated Mice

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