Damage Of Maternal Separation On Prefrontal Cortical And Hippocampal Dendritic Spines And Improvement Of Lactobacillus Plantarum WLPL04 On Cognitive Functions

Maternal separation produces a dramatic and negative impact on brain development and functions of offspring.A previous study shows that neonatal maternal separation(NMS)impairs prefrontal cortical myelination in rats via activating Wnt signaling pathway(Yang et al.,Cerebral Cortex,27:2871-2884,2017).Here,we report that NMS significantly reduced dendritic spines in layer 5 pyramidal cells of the medial prefrontal cortex(mPFC)and in CA1 pyramidal cells of the hippocampus,as revealed via Golgi-Cox staining technique.In accordance,NMS produced severe deficits in mPFC-and/or hippocampus-dependent behaviors and such deficits were still maintained in adulthood.For example,NMS rats exhibited increased anxiety in elevated plus maze,impaired novel object recognition and social interaction ability,and destroyed T-maze working memory and water maze spatial learning and memory.The present results indicate that NMS produces a negative and profound impact on the precise structures and cognitive functions of the mPFC and the hippocampus.Background/Aims The gut-brain axis is involved in the regulation of host metabolism,neurodevelopment and brain function.Intestinal microorganisms play an important role in regulating the neurodevelopment and brain functions of host by the gut-brain axis.Lactobacillus,one of the most representative intestinal probiotics,produces important effects on human physiological functions.Our previous studies revealed that Lactobacillus plantarum WLPL04 has a series of beneficial actions.However,its effects on brain functions are still unknown.The present study aimed to evaluate the potential effect of Lactobacillus plantarum WLPL04 on anxiety/depressive-like behaviors in chronically-restrained mice.Methods Newly-weaned C57BL/6 mice were exposed to chronic restraint stress for 4 weeks and raised daily with or without Lactobacillus plantarum WLPL04 water supplement.16 SrRNA sequencing was performed to analyze the intestinal flora structure.Animals were then behaviorally assessed for anxiety/depression and cognitive functions.Medial prefrontal cortical(m PFC)BDNF/Trk B and serum 5-hydroxytryptamine(5-HT)levels were examined using western blotting and ELISA.Results 16 SrRNA sequencing analysis showed that the chronic stress reduced the diversity and richness of intestinal flora,which were rescued by treatment with Lactobacillus plantarum WLPL04.The levels of BDNF and Trk B in the mPFC and the concentration of 5-HT in serum remained unchanged in chronically-restrained mice treated with Lactobacillus plantarum WLPL04.The chronic stress induced anxiety/depression-like behaviors and cognitive deficits,which were significantly alleviated by Lactobacillus plantarum WLPL04 treatment.Conclusions Lactobacillus plantarum WLPL04 has the potential to reverse the abnormal change in intestinal flora,alleviate the reduced levels of 5-HT,BDNF and TrkB,and rescue anxiety/depressive-like behaviors and cognitive dysfunctions induced by chronic stress in mice,providing an experimental basis for the therapeutic application of Lactobacillus plantarum on anxiety/depression.