Microglial Dysfunction in Autism Spectrum Disorder

Meng, Jian; Zhang, Lingliang; Zhang, Yun-wu

doi:10.1177/10738584241252576

Neuroscientist

2024

DOI: 10.1177/10738584241252576

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Microglial Dysfunction in Autism Spectrum Disorder

Jian Meng,

Lingliang Zhang,

Yun-wu Zhang

Abstract: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with onset in childhood. The molecular mechanisms underlying ASD have not yet been elucidated completely. Evidence has emerged to support a link between microglial dysfunction and the etiology of ASD. This review summarizes current research on microglial dysfunction in neuroinflammation and synaptic pruning, which are associated with altered transcriptomes and autophagy in ASD. Dysbiosis of gut microbiota in ASD and its correl… Show more

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Cited by 2 publications

References 143 publications

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Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease

Allen,

Morishita

2024

Sci. Adv.

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Frontal cortical circuits undergo prolonged maturation across childhood and adolescence; however, it remains unknown what specific changes are occurring at the circuit level to establish adult cognitive function. With the recent advent of circuit dissection techniques, it is now feasible to examine circuit-specific changes in connectivity, activity, and function in animal models. Here, we propose that the balance of local and long-range inputs onto frontal cognitive circuits is an understudied metric of circuit maturation. This review highlights research on a frontal-sensory attention circuit that undergoes refinement of local/long-range connectivity, regulated by circuit activity and neuromodulatory signaling, and evaluates how this process may occur generally in the frontal cortex to support adult cognitive behavior. Notably, this balance can be bidirectionally disrupted through various mechanisms relevant to psychiatric disorders. Pharmacological or environmental interventions to normalize or reset the local and long-range balance could hold great therapeutic promise to prevent or rescue cognitive deficits.

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Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease

Allen,

Morishita

2024

Sci. Adv.

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Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome

Asta,

Ricciardello,

Cucinotta

et al. 2024

J Neurodevelop Disord

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Background Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). Objectives To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. Methods 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. Results Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001). Conclusions We replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way.

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Microglial Dysfunction in Autism Spectrum Disorder

Cited by 2 publications

References 143 publications

Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease

Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease

Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome

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