Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

IF 4.3 2区 生物学 Q1 BIOLOGY Biological Research Pub Date : 2024-06-18 DOI:10.1186/s40659-024-00522-0
Bastián I Cortés, Rodrigo C Meza, Carlos Ancatén-González, Nicolás M Ardiles, María-Ignacia Aránguiz, Hideaki Tomita, David R Kaplan, Francisca Cornejo, Alexia Nunez-Parra, Pablo R Moya, Andrés E Chávez, Gonzalo I Cancino
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Abstract

Background: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.

Results: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.

Conclusions: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

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蛋白酪氨酸磷酸酶受体δ PTPRD的缺失会增加成年小鼠大脑皮层神经元的数量、损害突触功能并诱发类似自闭症的行为。
背景:大脑皮层负责许多高级认知功能。大脑皮层发育过程中的干扰会对大脑功能产生长期影响,并与脑部疾病的病因有关。我们之前发现,蛋白酪氨酸磷酸酶受体δ Ptprd 是大脑皮层发育的关键,它与几种人类神经发育障碍有遗传关联。Ptprd 的表达缺失会过度激活神经前体细胞中的促神经再生受体 TrkB 和 PDGFRβ,从而诱发胚胎和新生小鼠兴奋性神经元的异常增加。然而,这些改变是否会对成年期产生长期影响仍是未知数:结果:在这里,我们发现在 Ptprd+/- 或 Ptprd-/- 小鼠中,兴奋性神经元的发育增加会持续到成年,从而影响内侧前额叶皮层的兴奋性突触功能。同样,Ptprd 的杂合性或同源性也会诱导抑制性皮质 GABA 能神经元的增加,并损害抑制性突触传递。最后,Ptprd+/- 或 Ptprd-/- 小鼠表现出类似自闭症的行为,但没有学习和记忆障碍或焦虑:这些结果表明,Ptprd 的缺失会对大脑皮层神经元数量和突触功能产生长期影响,并可能对类似 ASD 的行为产生异常影响。
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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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