Bacterial infections activate autophagy and autophagy restricts pathogens such as
Haemophilus parasuis
through specific mechanisms. Autophagy is associated with the pathogenesis of
H. parasuis
. However, the mechanisms have not been clarified. Here, we monitored autophagy processes using confocal microscopy, western blot, and transmission electron microscopy (TEM) and found that
H. parasuis
SH0165 (high-virulent strain) but not HN0001 (non-virulent strain) infection enhanced autophagy flux. The AMPK/mTOR autophagy pathway was required for autophagy initiation and ATG5, Beclin-1, ATG7, and ATG16L1 emerged as important components in the generation of the autophagosome during
H. parasuis
infection. Moreover, autophagy induced by
H. parasuis
SH0165 turned to fight against invaded bacteria and inhibit inflammation. Then we further demonstrated that autophagy blocked the production of the cytokines IL-8, CCL4, and CCL5 induced by SH0165 infection through the inhibition of NF-κB, p38, and JNK MAPK signaling pathway. Therefore, our findings suggest that autophagy may act as a cellular defense mechanism in response to
H. parasuis
and provide a new way that autophagy protects the host against
H. parasuis
infection.
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and the most common known cause of autism spectrum disorders. FXS patients exhibit severe syndromic features and behavioral alterations, including anxiety, hyperactivity, impulsivity, and aggression, in addition to cognitive impairment and seizures. At present, there are no effective treatments or cures for FXS. Previously, we have found the divergence of BDNF-TrkB signaling trajectories is associated with spine defects in early postnatal developmental stages of Fmr1 KO mice. Here, young fragile X mice were intraperitoneal injection of 7,8-Dihydroxy avone (7,8-DHF), which is a high a nity tropomyosin receptor kinase B (TrkB) agonist. 7,8-DHF ameliorated morphological abnormities in dendritic spine and synaptic structure, and rescued synaptic and hippocampus-dependent cognitive dysfunction in young FXS mice. These observed improvement of 7,8-DHF involved decreased protein levels of BDNF, p-TrkB Y816 , p-PLCγ, and p-CaMKII in the hippocampus. In addition, 7,8-DHF intervention in primary hippocampal neurons increased p-TrkB Y816 through activating the PLCγ1-CaMKII signaling pathway leading to improvement of neuronal morphology.This study is the rst to account for early life synaptic impairments, neuronal morphological and cognitive delays in FXS in response to the abnormal BDNF-TrkB pathway. Present studies provide novel evidences about the effective early intervention in FXS mice at developmental stages as a strategy to produce powerful impacts on neural development, synaptic plasticity and behaviors.
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and the most common known cause of autism spectrum disorders. FXS patients exhibit severe syndromic features and behavioral alterations, including anxiety, hyperactivity, impulsivity, and aggression, in addition to cognitive impairment and seizures. At present, there are no effective treatments or cures for FXS. Previously, we have found the divergence of BDNF-TrkB signaling trajectories is associated with spine defects in early postnatal developmental stages of Fmr1 KO mice. Here, young fragile X mice were intraperitoneal injection of 7,8-Dihydroxyflavone (7,8-DHF), which is a high affinity tropomyosin receptor kinase B (TrkB) agonist. 7,8-DHF ameliorated morphological abnormities in dendritic spine and synaptic structure, and rescued synaptic and hippocampus-dependent cognitive dysfunction in young FXS mice. These observed improvement of 7,8-DHF involved decreased protein levels of BDNF, p-TrkBY816, p-PLCγ, and p-CaMKII in the hippocampus. In addition, 7,8-DHF intervention in primary hippocampal neurons increased p-TrkBY816 through activating the PLCγ1-CaMKII signaling pathway leading to improvement of neuronal morphology. This study is the first to account for early life synaptic impairments, neuronal morphological and cognitive delays in FXS in response to the abnormal BDNF-TrkB pathway. Present studies provide novel evidences about the effective early intervention in FXS mice at developmental stages as a strategy to produce powerful impacts on neural development, synaptic plasticity and behaviors.
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