Minocycline improves autism-related behaviors by modulating microglia polarization in a mouse model of autism

Luo, Yi; Lv, Keyi; Du, Zhulin; Zhang, Dandan; Chen, Mei; Luo, Jia; Wang, Lian; Liu, Tianyao; Gong, Hong; Fan, Xiaotang

doi:10.1016/j.intimp.2023.110594

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…A common theme of microglial dyshomeostasis emerged from these studies, prompting strategies targeting microglia to reverse or delay disease progression. In support of this possibility, treatment using minocycline, a tetracycline derivative, in a BTBR ASD mouse model restored microglia to their homeostatic state and rescued ASD-related sociability changes and repetitive behaviors [37]. As also noted earlier, a further study treated HD patients with cannabinoids which act on cannabinoid receptors, and found that this improved HD related motor symptoms via microglial mechanisms [38].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 56%

Microglial Dyshomeostasis: A Common Substrate in Neurodevelopmental and Neurodegenerative Diseases

Furlan,

MacAuslan,

et al. 2024

Neuroglia

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Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are clinically distinct, yet share synaptic dysfunction as a common brain pathophysiology. Neurodegenerative diseases such as Huntington’s disease (HD) entail a neuroinflammatory cascade of molecular and cellular events which can contribute to the death of neurons. Emerging roles for supportive glial cells such as microglia and astrocytes in the ongoing regulation of neural synapses and brain excitability raise the possibility that some of the synaptic pathology and/or inflammatory events could be a direct consequence of malfunctioning glial cells. Focusing on microglia, we cross-examined 12 recently published studies in which microglial dysfunction was induced/identified in a cell-autonomous manner and its functional consequence on neural development, brain volume, functional connectivity, inflammatory response and synaptic regulation were evaluated; in many cases, the onset of symptoms relevant to all three neurodevelopmental disorders were assessed behaviorally. Challenging the classic notion of microglial activation as an inflammatory response to neuropathology, our compilation clarifies that microglial dyshomeostasis itself can consequently disrupt neural homeostasis, leading to neuropathology and symptom onset. This further warranted defining the molecular signatures of context-specific microglial pathology relevant to human diseases.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 56%

Microglial Dyshomeostasis: A Common Substrate in Neurodevelopmental and Neurodegenerative Diseases

Furlan,

MacAuslan,

et al. 2024

Neuroglia

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“…35 Previous studies that analyzed reciprocal social interactions like nose-to-nose sniffing, nose-to-head sniffing and body sniffing of Fmr1 knockout mice models generally linked a reduction in sniffing time with sociability deficits. 36,37 Although some sniffing behavior like anogenital sniffing has been correlated with the collection of odor information and sexual interest, the reason underlying other individual sniffing behaviors remains unexplored. 38 Deep learning approaches, as displayed by the software used in the present study (REF), enabled the detection and tracking of changes in the positions of defined body parts, that allowed for the investigation of social interactions in a more natural setting.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Dynamics of Social Interactions During the Juvenile Stage in a Mouse Model of Fragile X Syndrome

Bae,

Wang,

Abdullah

et al. 2024

Preprint

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IntroductionFragile X Syndrome (FXS), caused by mutations in theFmr1gene, is a neurodevelopmental condition linked to cognitive and behavioral differences, including atypical interactions and heightened anxiety-like responses in social settings. Previous studies that used FXS mouse models focused mostly on adulthood but not on behaviors displayed by juvenile mice. This is especially concerning considering the extensive body of research conducted in children and adolescents with FXS, which indicates dynamic neurodevelopmental changes from childhood to adulthood. Thus, it is crucial to study how FXS affects social interactions during the juvenile stage, in both female and male mice. In this study, we compared the social behavior ofFmr1knockout (KO) mice, a model of FXS, with wild-type (WT) mice of the C57BL/6J strain.MethodsWe examined both male and female juvenile mice at postnatal day 40 (P40). Social interaction tests were carried out using two mice of the same sex and genotype, who previously had not encountered each other, and were allowed to interact freely in an empty chamber for 10 minutes. Their behaviors were recorded by an overhead camera for 10 minutes. Key social behaviors such as head, body, anogenital sniffing, and physical touch, as well as distance traveled, were analyzed with a recently developed marker-less tracking software.ResultsResults from the social interaction tests showed pronounced sex and genotype differences between juvenile females and males of both the WT and KO genotypes. Overall, sex differences were found in all the behavioral parameters that were measured. Notably, the KO females engaged in more social interaction events compared to WT females in each social behavior. On the other hand, there were no significant differences observed between the WT and KO males.DiscussionThese results highlight the importance of considering the differences that arise during the juvenile stage inFmr1KO mouse model, suggesting that early post-natal phases may be a promising window for therapeutic interventions.

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“…Here, we summarize a few relevant aspects of the glial cell role in ASD. Results of the two types of cells are reported, first concerning their separate effects [58][59][60][61][62] and then working together with coordinate effects [63,64].…”

Section: Contribution Of Glial Cellsmentioning

confidence: 99%

Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies

Lamanna,

Meldolesi

2024

IJMS

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Autism spectrum disorder (ASD), affecting over 2% of the pre-school children population, includes an important fraction of the conditions accounting for the heterogeneity of autism. The disease was discovered 75 years ago, and the present review, based on critical evaluations of the recognized ASD studies from the beginning of 1990, has been further developed by the comparative analyses of the research and clinical reports, which have grown progressively in recent years up to late 2023. The tools necessary for the identification of the ASD disease and its related clinical pathologies are genetic and epigenetic mutations affected by the specific interaction with transcription factors and chromatin remodeling processes occurring within specific complexes of brain neurons. Most often, the ensuing effects induce the inhibition/excitation of synaptic structures sustained primarily, at dendritic fibers, by alterations of flat and spine response sites. These effects are relevant because synapses, established by specific interactions of neurons with glial cells, operate as early and key targets of ASD. The pathology of children is often suspected by parents and communities and then confirmed by ensuing experiences. The final diagnoses of children and mature patients are then completed by the combination of neuropsychological (cognitive) tests and electro-/magneto-encephalography studies developed in specialized centers. ASD comorbidities, induced by processes such as anxieties, depressions, hyperactivities, and sleep defects, interact with and reinforce other brain diseases, especially schizophrenia. Advanced therapies, prescribed to children and adult patients for the control of ASD symptoms and disease, are based on the combination of well-known brain drugs with classical tools of neurologic and psychiatric practice. Overall, this review reports and discusses the advanced knowledge about the biological and medical properties of ASD.

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Minocycline improves autism-related behaviors by modulating microglia polarization in a mouse model of autism

Cited by 14 publications

References 63 publications

Microglial Dyshomeostasis: A Common Substrate in Neurodevelopmental and Neurodegenerative Diseases

Microglial Dyshomeostasis: A Common Substrate in Neurodevelopmental and Neurodegenerative Diseases

Exploring the Dynamics of Social Interactions During the Juvenile Stage in a Mouse Model of Fragile X Syndrome

Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies

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