Inflammation is an established etiopathogenesis factor of infantile spasms（IS）, a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in...Inflammation is an established etiopathogenesis factor of infantile spasms（IS）, a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment（adreno-cortico-tropic-hormone（ACTH） or PMX53）or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53（an antagonist of the complement C5 a receptor） in restoring the normal transcriptome was not expected. In addition to the childhood epilepsy, the recovery of the neurotransmission genomic fabrics by PMX53 also gives hope for the autism spectrum disorders that share a high comorbidity with IS. Our results revealed significant sex dichotomy in both IS-associated transcriptomic alterations（males more affected） and in the efficiency of PMX53 anti-inflammatory treatment（better for males）. Our data further suggest that anti-inflammatory treatments correcting alterations in the inflammatory transcriptome may become successful therapies for refractory epilepsies.展开更多
Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-cal...Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.展开更多
基金supported by Citizens United for Research in Epilepsy (CURE) Infantile Spasms Research Initiative(to LV and DAI)NIH grant NS-072966(to LV)
文摘Inflammation is an established etiopathogenesis factor of infantile spasms（IS）, a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment（adreno-cortico-tropic-hormone（ACTH） or PMX53）or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53（an antagonist of the complement C5 a receptor） in restoring the normal transcriptome was not expected. In addition to the childhood epilepsy, the recovery of the neurotransmission genomic fabrics by PMX53 also gives hope for the autism spectrum disorders that share a high comorbidity with IS. Our results revealed significant sex dichotomy in both IS-associated transcriptomic alterations（males more affected） and in the efficiency of PMX53 anti-inflammatory treatment（better for males）. Our data further suggest that anti-inflammatory treatments correcting alterations in the inflammatory transcriptome may become successful therapies for refractory epilepsies.
文摘Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.
