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. 2024 Jan-Dec;16(1):2359501.
doi: 10.1080/19490976.2024.2359501. Epub 2024 Jun 6.

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention

Chih-Ming Chen  1   2 , Chien-Chen Wu  2 , Yebeen Kim  3 , Wei-Yu Hsu  3 , Ying-Chieh Tsai  1 , Shu-Ling Chiu  3
Affiliations

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention

Chih-Ming Chen et al. Gut Microbes. 2024 Jan-Dec.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

Keywords: ASD mouse model; Gut microbiota; dendritic arborization; hippocampus; neuronal connectivity; paraventricular nucleus; valproic acid.

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Conflict of interest statement

C.-M.C., and C.-C.W. were employed by Bened Biomedical Co., Ltd. at the time of the study. Y.-C.T. serves as a consultant and owns stock in Bened Biomedical Co., Ltd. None of the other authors had any personal or financial conflict of interest. The funder had no role in the design of the study; in the collection, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1.
Figure 1.
PS128 rescues behavioral abnormalities of the VPA mice.
Figure 2.
Figure 2.
PS128 restores dendritic morphology of VPA mice.
Figure 3.
Figure 3.
PS128 rescues spine loss in VPA mice.
Figure 4.
Figure 4.
PS128 restores reduced kinase activities and synaptic glutamate receptors in the hippocampus of VPA mice.
Figure 5.
Figure 5.
PS128 restores oxytocin expression in the PVN of VPA mice.
Figure 6.
Figure 6.
PS128 loses ability to rescue VPA-induced behaviors in mice lacking oxytocin receptors.
Figure 7.
Figure 7.
PS128 increases Bifidobacterium abundance in the gut, which correlates with improvements in ASD-associated behaviors in VPA mice.
See this image and copyright information in PMC

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