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Cytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits

ABSTRACT: Cytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits

PROVIDER: PRJNA1279066 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR34026167_1.fastq.gz	Fastqsanger.gz
	SRR34026167_2.fastq.gz	Fastqsanger.gz
	SRR34026168_1.fastq.gz	Fastqsanger.gz
	SRR34026168_2.fastq.gz	Fastqsanger.gz

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Cytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits

Project description:We have employed a single-cell sequencing approach using 10x Genomics scRNAseq to study the impact of Disc1 locus impairment (LI) on adult microglia. This study revealed that actin dysregulation and enhanced phagocytosis characterize the transcriptomic profile of Disc1 LI microglia.

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Activation of hypothalaActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseasemic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseaseActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's disease

Project description:Patients with Alzheimer’s disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether modulating AHN is sufficient to improve these cognitive and noncognitive symptoms in AD remains elusive. Here we report that chronic stimulation of hypothalamic supramammillary nucleus (SuM) during early AD restores AHN in an otherwise impaired neurogenic niche. Strikingly, activation of SuM-enhanced adult-born neurons (ABNs) is sufficient to restore memory and emotion deficits in 5×FAD mice. Interestingly, activation of SuM-enhanced ABNs in AD mice increases CA3 and CA1 activity. To probe ABN-activity-dependent changes, we performed quantitative phosphoproteomics and found activation of SuM-enhanced ABNs promotes activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis. Functional assays further confirm increased CA1 long-term potentiation and enhanced microglia phagocytosis of plaques upon activation of SuM-enhanced ABNs. Our findings reveal a robust AHN-promoting strategy that is sufficient to restore AD-associated deficits and highlight ABN-activity-dependent mechanisms underlying functional improvement in AD.

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SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients.

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