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High-frequency head impacts cause chronic synaptic adaptations and long-term cognitive impairment [24h post-HFHI]

ABSTRACT: High-frequency head impacts cause chronic synaptic adaptations and long-term cognitive impairment [24h post-HFHI]

PROVIDER: PRJNA695799 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13575830_1.fastq.gz	Fastqsanger.gz
	SRR13575830_2.fastq.gz	Fastqsanger.gz
	SRR13575831_1.fastq.gz	Fastqsanger.gz
	SRR13575831_2.fastq.gz	Fastqsanger.gz
	SRR13575832_1.fastq.gz	Fastqsanger.gz

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High-frequency head impacts cause chronic synaptic adaptations and long-term cognitive impairment [24h post-HFHI]

Project description:The goal of this study is to use bulk RNA-sequencing of to observe the effects of High Frequency Head Impacts contibuting to cognitive dysfunction in mice. Our results show HF-HI can alter brain function through synaptic adaptation. HF-HI mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling reveals that synapses are a primary target of this effect.

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Project description:Meal frequency regulates postprandial glucose and insulin responses, which may affect substrate partitioning and thus weight control. This study investigated the effects of meal frequency on the metabolic and transcriptomic profiles in subjects with impaired glucose tolerance (IGT). Eleven IGT (2h glucose; 9.0±0.3mmol/L) men stayed 2x 36 hours in a respiration chamber to measure substrate partitioning. All subjects randomly received two isoenergetic diets with a low meal frequency (3x-LFr) or a high meal frequency (14x-HFr) consisting of 15 En% prot, 30 En% fat, and 55 En% carb. Total glucose output (AUC), carbohydrate oxidation and whole body RQ significantly decreased, and FFA levels increased in the LFr diet. The HFr diet resulted in an up-regulation in expression of genes involved in immune function and inflammation after 24h in PBMCs and muscle tissue. Expression of genes involved in PPAR signalling, OXPHOS, and glutathione metabolism were up-regulated in the HFr diet in muscle tissue only. In conclusion, the LFr diet improved the metabolic and transcriptomic profiles, and appetite control compared to the HFr diet. This suggests that a LFr diet might be an effective dietary strategy with anti-inflammatory characteristics to increase metabolic flexibility and body weight control in IGT subjects.

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High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.

Project description:Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.

| S-EPMC8110563 | biostudies-literature

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