2. Academic Validation
  3. Prenatal alcohol exposure enhanced alcohol preference and susceptibility to PTSD in a sex-dependent manner through the synaptic HCN1 channel

Prenatal alcohol exposure enhanced alcohol preference and susceptibility to PTSD in a sex-dependent manner through the synaptic HCN1 channel

  • J Affect Disord. 2022 Dec 29;324:143-152. doi: 10.1016/j.jad.2022.12.069.
Hui Yao 1,  Changliang Wang 2,  Zhixiu Xia 3
Affiliations

Affiliations

  • 1 Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, P. R. China.
  • 2 The People's Procuratorate of Liaoning Province Judicial Authentication Center, No. 46, Cong San East Road, Shenyang, Liaoning 110032, PR China.
  • 3 Colorectal Tumor Surgery Ward, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. Electronic address: [email protected].
PMID: 36587902 DOI: 10.1016/j.jad.2022.12.069
Abstract

Background: Prenatal alcohol exposure (PAE) adversely affects the neurobiological and behavioral functions of offspring. Increasing evidence indicates that alcohol-use disorders and post-traumatic stress disorder (PTSD) commonly co-occur. Enhanced function of hyperpolarization-activated gated channel 1 (HCN1) may be involved in the pathogenesis of PTSD. This study aimed to explore the effect of PAE on fear extinction, spontaneous recovery, alcohol preference, and function of HCN1 channels in offspring of both sexes.

Methods: The PAE model was established with a 20 % (m/V) ethanol solution, and offspring were treated with 0.5, 1, and 2 μg/mL ZD7288 to block the HCN1 channel. Behavioral tests were used to detect the mental state and fear of extinction of the mice. Western blot was used to detect HCN1 expression in the synaptosomes. The BDNF/TrkB-pmTOR pathway was also examined.

Results: ZD7288 administration ameliorated PAE-induced impairment of fear extinction and depression-like behavior. ZD7288 administration also alleviated PAE-induced inhibition of the HCN1 channel in the prefrontal cortex (PFC) and the BDNF/TrkB-pmTOR pathway in the hippocampus of offspring. In addition, the therapeutic effect of ZD7288 in males was better than that in females.

Conclusions: Overall, these results suggest that PAE enhances alcohol preference and susceptibility to PTSD through synaptic HCN1 channels in the PFC. In addition, ZD7288 may be a promising candidate for preventing alcohol-associated PTSD-like syndrome, particularly in males.

Limitations: The effects of ZD7288 were only studied in PAE Animals and not in healthy Animals.

Keywords

BDNF; HCN1 channel; PAE; PTSD; Synaptosome.

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