1. Academic Validation
  2. Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice

Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice

  • Mol Psychiatry. 2024 May 13. doi: 10.1038/s41380-024-02596-4.
Jun Ju # 1 Xuanyi Li # 1 Yifan Pan 1 Jun Du 2 Xinyi Yang 1 Siqi Men 1 Bo Liu 1 Zhenyu Zhang 1 Haolin Zhong 1 Jinyuan Mai 1 Yizheng Wang 3 Sheng-Tao Hou 4
Affiliations

Affiliations

  • 1 Brain Research Centre, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, 1088 Xueyuan Blvd, Nanshan District, Shenzhen, 518055, Guangdong, PR China.
  • 2 The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850, Beijing, China.
  • 3 Huashan Hospital, Fudan University, Shanghai, PR China.
  • 4 Brain Research Centre, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, 1088 Xueyuan Blvd, Nanshan District, Shenzhen, 518055, Guangdong, PR China. hou.st@sustech.edu.cn.
  • # Contributed equally.
Abstract

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and Others demonstrated that visual sensory stimulation using rhythmic 40 Hz LIGHT flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz LIGHT flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz LIGHT stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz LIGHT treatment. Importantly, the 40 Hz LIGHT flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz LIGHT flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz LIGHT flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz LIGHT flicker treatment. The 40 Hz LIGHT stimulation warrants further development as a non-invasive ASD therapeutics.

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