SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice

Xiang, Ludan; Qian, Wei; Sun, Huankun; Miao, Xuemeng; Lv, Zhaoting; Liu, Huitao; Chen, Lan; Gu, Yanrou; Chen, Jianjun; Zhou, Siyao; Jiang, Hua; Du, Siyu; Zhou, Yixin; Dong, Hui; Fan, Yiren; Miao, Shuangda; Qi, Lü; Chang, Liyun; Wang, Hui; Lu, Yi; Xu, Xingxing; Wang, Wei; Huang, Zhihui

doi:10.1038/s41419-022-05083-2

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…Consistent with previous study [ 45 ], the present study found that SARM1 was mainly expressed in brain neurons, and the expression of neuronal SARM1 was decreased in 9-month-old APP/PS1 model mice ( Fig. 1 ).…”

Section: Discussionsupporting

confidence: 93%

“…Some previous studies have shown that in SARM1 knockdown mice, dendritic arbors of neurons were less complex, and suggested that SARM1 is required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization [ 47 ]. Our previous study has shown that parvalbumin-positive interneurons (PVI)-specific conditional SARM1 deletion (SARM1 PV -CKO) mice exhibited autism-like behaviors and a reduction in the number of PVIs due to apoptosis, suggesting that SARM1 deficiency in PVIs may contribute to the pathogenesis of autism spectrum disorder [ 45 ]. However, our recent studies suggested that there was no significant difference in the neuronal number and distribution in the spinal cords between SARM1 f/f and SARM1 Nestin -CKO mice.…”

Section: Discussionmentioning

confidence: 99%

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SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease

Miao¹,

Qian²,

Du³

et al. 2024

Aging and disease

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Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1 Nestin -CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aβ deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1 Nestin -CKO mice, thereby alleviating the cognitive decline, Aβ deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease

Miao¹,

Qian²,

Du³

et al. 2024

Aging and disease

Self Cite

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“…For example, the emergence of PV neurons in the visual cortex of rodents coincides with the onset of the critical period for visual plasticity (del Río et al, 1994;Sugiyama et al, 2008;Takesian and Hensch, 2013;Cisneros-Franco et al, 2020), and manipulations of PV expression affect plasticity and the timing of critical periods for sensory and cognitive systems (Murray et al, 2015;Wöhr et al, 2015;Hou et al, 2017;Xia et al, 2017;Cisneros-Franco and de Villers-Sidani, 2019;Deng et al, 2019;Miranda et al, 2022). Furthermore, manipulations of PV neuron activity affects neural dynamics across various brain systems (e.g., Spiro et al, 1999;Cardin et al, 2009;Sohal et al, 2009;Pyka et al, 2011;Albéri et al, 2013;Liu et al, 2013;Hu et al, 2014;Xue et al, 2014;Wöhr et al, 2015;Xia et al, 2017;Carceller et al, 2020), and PV neuron dysfunction can lead to cognitive and behavioral dysfunctions (Cardin et al, 2009;Sohal et al, 2009;Hu et al, 2014;Wöhr et al, 2015;Enwright et al, 2016;Favuzzi et al, 2017;Xiang et al, 2022). Therefore, it is important to reveal the factors that influence PV expression.…”

Section: Introductionmentioning

confidence: 99%

Cross-species conservation in the regulation of parvalbumin by perineuronal nets

Wang,

Wan,

Storch

et al. 2023

Front. Neural Circuits

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Parvalbumin (PV) neurons play an integral role in regulating neural dynamics and plasticity. Therefore, understanding the factors that regulate PV expression is important for revealing modulators of brain function. While the contribution of PV neurons to neural processes has been studied in mammals, relatively little is known about PV function in non-mammalian species, and discerning similarities in the regulation of PV across species can provide insight into evolutionary conservation in the role of PV neurons. Here we investigated factors that affect the abundance of PV in PV neurons in sensory and motor circuits of songbirds and rodents. In particular, we examined the degree to which perineuronal nets (PNNs), extracellular matrices that preferentially surround PV neurons, modulate PV abundance as well as how the relationship between PV and PNN expression differs across brain areas and species and changes over development. We generally found that cortical PV neurons that are surrounded by PNNs (PV+PNN neurons) are more enriched with PV than PV neurons without PNNs (PV-PNN neurons) across both rodents and songbirds. Interestingly, the relationship between PV and PNN expression in the vocal portion of the basal ganglia of songbirds (Area X) differed from that in other areas, with PV+PNN neurons having lower PV expression compared to PV-PNN neurons. These relationships remained consistent across development in vocal motor circuits of the songbird brain. Finally, we discovered a causal contribution of PNNs to PV expression in songbirds because degradation of PNNs led to a diminution of PV expression in PV neurons. These findings reveal a conserved relationship between PV and PNN expression in sensory and motor cortices and across songbirds and rodents and suggest that PV neurons could modulate plasticity and neural dynamics in similar ways across songbirds and rodents.

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“…Both SARM1 and ASK1 regulate Toll-like receptor (TLR) signaling, a key signaling arm of innate immunity ( Liu et al, 2014 ; Matsuzawa, 2017 ), and act via JNK to promote “forgetting” in C. elegans olfactory neurons ( Inoue et al, 2013 ). Loss of SARM1 also leads to impairments in synaptic plasticity ( Lin et al, 2014 ) and loss of parvalbumin neurons associated with autism-like behaviors ( Xiang et al, 2022 ).…”

Section: Sarm1-regulated Signaling Mediates Diverse Functions Includi...mentioning

confidence: 99%

Multifaceted roles of SARM1 in axon degeneration and signaling

Waller

Collins

2022

Front. Cell. Neurosci.

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Axons are considered to be particularly vulnerable components of the nervous system; impairments to a neuron’s axon leads to an effective silencing of a neuron’s ability to communicate with other cells. Nervous systems have therefore evolved plasticity mechanisms for adapting to axonal damage. These include acute mechanisms that promote the degeneration and clearance of damaged axons and, in some cases, the initiation of new axonal growth and synapse formation to rebuild lost connections. Here we review how these diverse processes are influenced by the therapeutically targetable enzyme SARM1. SARM1 catalyzes the breakdown of NAD+, which, when unmitigated, can lead to rundown of this essential metabolite and axonal degeneration. SARM1’s enzymatic activity also triggers the activation of downstream signaling pathways, which manifest numerous functions for SARM1 in development, innate immunity and responses to injury. Here we will consider the multiple intersections between SARM1 and the injury signaling pathways that coordinate cellular adaptations to nervous system damage.

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SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice

Cited by 9 publications

References 42 publications

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease

Cross-species conservation in the regulation of parvalbumin by perineuronal nets

Multifaceted roles of SARM1 in axon degeneration and signaling

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