Dendritic beading during early brain development impairs signal transmission and synaptic plasticity.

IF 5.7 2区医学 Q1 NEUROSCIENCES

Acta Neuropathologica Communications Pub Date : 2025-10-06 DOI:10.1186/s40478-025-02123-8

Pratyush Suryavanshi, Satya Murthy Tadinada, Samuel Baule, Naisha Jhaveri-Cruz, Ted Abel, Joseph Glykys

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Abstract

Excessive glutamate receptor activation during brain pathologies causes varicose dendritic swelling, also known as "dendritic beading", yet its impact on developing brain circuits is poorly understood. Using field electrophysiology and two-photon imaging in awake, behaving mice and acute brain slices (P11-19), we found that severe and recurrent seizure-like activity (induced by NMDA and 4-aminopyridine) resulted in widespread, long-lasting dendritic beading and spine loss in cortical and hippocampal neurons, with localization patterns distinct from those described in adults. Beads showed persistently high calcium levels and stopped the spread of dendritic calcium signals. Dendritic beads suppressed hippocampal evoked field potentials, followed by only partial recovery, and reduced hippocampal long-term potentiation. Clinically used hyperosmotic treatments (mannitol or hypertonic saline) reduced seizure-induced beading and restored dendritic signal propagation. These findings suggest that seizure-induced dendritic beading disrupts circuit function and synaptic plasticity and may contribute to cognitive deficits after early-life seizures.

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早期大脑发育中的树突串珠损害信号传递和突触可塑性。

在脑部病变期间，过度的谷氨酸受体激活会导致静脉曲张的树突肿胀，也被称为“树突珠状”，但其对大脑回路发育的影响尚不清楚。通过对清醒、行为正常的小鼠和急性脑切片（P11-19）进行场电生理学和双光子成像，我们发现严重和反复发作的癫痫样活动（由NMDA和4-氨基吡啶诱导）导致皮层和海马神经元广泛、持久的树突珠状突起和脊柱丢失，其定位模式与成人不同。小珠子显示出持续的高钙水平，并阻止了树突钙信号的扩散。树突珠抑制海马诱发场电位，随后仅部分恢复，海马长时程增强减弱。临床上使用高渗治疗（甘露醇或高渗盐水）可减少癫痫引起的脑珠状反应，恢复树突信号传播。这些发现表明，癫痫引起的树突串珠破坏了电路功能和突触可塑性，并可能导致早期癫痫发作后的认知缺陷。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine

CiteScore

11.20

自引率

2.80%

发文量

162

审稿时长

8 weeks

期刊介绍： "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.