Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex

Blagburn-Blanco, Sara V.; Chappell, Megan S.; Biase, Lindsay M. De; DeNardo, Laura A

doi:10.3389/fnmol.2022.965756

Cited by 6 publications

(7 citation statements)

References 134 publications

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“…Conversely, microglial contact with dendritic spines could also increase the possibility of spine retraction by modifying the local extracellular matrix and reducing synaptic stability. Dendritic spine dynamics and synaptic AMPAR transport could be influenced by BDNF and TNFα, respectively, secreted by microglia, which perform their function of partially encapsulating synapses rather than engulfing them ( Blagburn-Blanco et al, 2022 ).…”

Section: Microglia Contribute To Neuroinflammation In Asd By Releasin...mentioning

confidence: 99%

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Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Xiong

Chen

2023

Front. Neurosci.

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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes in ASD has received increasing attention. Microglia prune the synapses or respond to injury by sequestrating the injury site and expressing inflammatory cytokines. Astrocytes maintain homeostasis in the brain microenvironment through the uptake of ions and neurotransmitters. However, the molecular link between ASD and microglia and, or astrocytes remains unknown. Previous research has shown the significant role of microglia and astrocytes in ASD, with reports of increased numbers of reactive microglia and astrocytes in postmortem tissues and animal models of ASD. Therefore, an enhanced understanding of the roles of microglia and astrocytes in ASD is essential for developing effective therapies. This review aimed to summarize the functions of microglia and astrocytes and their contributions to ASD.

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Section: Microglia Contribute To Neuroinflammation In Asd By Releasin...mentioning

confidence: 99%

“…More importantly, inhibitory neuronal function and synapses are modulated by specific ASD risk genes. For example, most of the behavioral features of RTT were reproducible when the risk MECP2 gene was deleted from all GABAergic interneurons ( Blagburn-Blanco et al, 2022 ).…”

Section: Microglia Contribute To Neuroinflammation In Asd By Releasin...mentioning

confidence: 99%

Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Xiong

Chen

2023

Front. Neurosci.

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“…Little is known concerning the microglia’s influence on mPFC development and its function, such as social behavior [ 53 ]. As such, microglia are receiving significantly more attention in psychiatric research [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

Komori,

Okamura,

Ikehara

et al. 2024

Mol Psychiatry

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Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors—associated with the medial prefrontal cortex (mPFC)—has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21–p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf—regulated using doxycycline at different time points—underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45–p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

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“…As such, microglia are receiving significantly more attention in psychiatric research [ 54 , 55 ]. In particular, understanding microglia’s role in the mPFC circuit formation is essential due to the critical implication of the mPFC in the pathobiology of neuropsychiatric disorders [ 53 , 56 – 58 ]. In this study, we first demonstrated that j-SI mice during p21–p35 had increased MG- Bdnf expression and reduced sociability, consistent with previous studies [ 12 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

Makinodan

Komori²,

Okamura³

et al. 2023

Preprint

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Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors—associated with the medial prefrontal cortex (mPFC)—has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21–p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf—regulated using doxycycline at different time points—underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45–p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages.

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Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex

Cited by 6 publications

References 134 publications

Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

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