Regulation Of Synaptic Proteins Research Articles

Gene Expression at the Tripartite Synapse: Bridging the Gap Between Neurons and Astrocytes.

Astrocytes, a major class of glial cells, are an important element at the synapse where they engage in bidirectional crosstalk with neurons to regulate numerous aspects of neurotransmission, circuit function, and behavior. Mutations in synapse-related genes expressed in both neurons and astrocytes are central factors in a vast number of neurological disorders, making the proteins that they encode prominent targets for therapeutic intervention. Yet, while the roles of many of these synaptic proteins in neurons are well established, the functions of the same proteins in astrocytes are largely unknown. This gap in knowledge must be addressed to refine therapeutic approaches. In this chapter, we integrate multiomic meta-analysis and a comprehensive overview of current literature to show that astrocytes express an astounding number of genes that overlap with the neuronal and synaptic transcriptomes. Further, we highlight recent reports that characterize the expression patterns and potential novel roles of these genes in astrocytes in both physiological and pathological conditions, underscoring the importance of considering both cell types when investigating the function and regulation of synaptic proteins.

Acupuncture Interventions for Alzheimer's Disease and Vascular Cognitive Disorders: A Review of Mechanisms.

Cognitive impairment (CI) related to Alzheimer's disease (AD) and vascular cognitive disorders (VCDs) has become a key problem worldwide. Importantly, CI is a neuropsychiatric abnormality mainly characterized by learning and memory impairments. The hippocampus is an important brain region controlling learning and memory. Recent studies have highlighted the effects of acupuncture on memory deficits in AD and VCDs. By reviewing the literature published on this topic in the past five years, the present study intends to summarize the effects of acupuncture on memory impairment in AD and VCDs. Focusing on hippocampal synaptic plasticity, we reviewed the mechanisms underlying the effects of acupuncture on memory impairments through regulation of synaptic proteins, AD characteristic proteins, intestinal microbiota, neuroinflammation, microRNA expression, orexin system, energy metabolism, etc., suggesting that hippocampal synaptic plasticity may be the common as well as the core link underlying the above mechanisms. We also discussed the potential strategies to improve the effect of acupuncture. Additionally, the effects of acupuncture on synaptic plasticity through the regulation of vascular–glia–neuron unit were further discussed.

Proteomics Analysis of Dorsal Striatum Reveals Changes in Synaptosomal Proteins following Methamphetamine Self-Administration in Rats.

Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain’s reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that result from drug use. Therefore, using large scale proteomics studies we aim to identify global protein expression changes within the dorsal striatum, a key brain region involved in the modulation of addiction. We performed LC-MS/MS analyses on rat striatal synaptosomes following 30 days of methamphetamine self-administration (2 hours/day) and 14 days abstinence. We identified a total of 84 differentially-expressed proteins with known roles in neuroprotection, neuroplasticity, cell cytoskeleton, energy regulation and synaptic vesicles. We identify significant expression changes in stress-induced phosphoprotein and tubulin polymerisation-promoting protein, which have not previously been associated with addiction. In addition, we confirm the role of amphiphysin and phosphatidylethanolamine binding protein in addiction. This approach has provided new insight into the effects of methamphetamine self-administration on synaptic protein expression in a key brain region associated with addiction, showing a large set of differentially-expressed proteins that persist into abstinence. The mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD001443.

Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons

Although fucose-alpha(1-2)-galactose [Fucalpha(1-2)Gal] carbohydrates have been implicated in cognitive processes such as long-term memory, the molecular mechanisms by which these sugars influence neuronal communication are not well understood. Here, we present molecular insights into the functions of Fucalpha(1-2)Gal sugars, demonstrating that they play a role in the regulation of synaptic proteins and neuronal morphology. We show that synapsins Ia and Ib, synapse-specific proteins involved in neurotransmitter release and synaptogenesis, are the major Fucalpha(1-2)Gal glycoproteins in mature cultured neurons and the adult rat hippocampus. Fucosylation has profound effects on the expression and turnover of synapsin in cells and protects synapsin from degradation by the calcium-activated protease calpain. Our studies suggest that defucosylation of synapsin has critical consequences for neuronal growth and morphology, leading to stunted neurite outgrowth and delayed synapse formation. We also demonstrate that Fucalpha(1-2)Gal carbohydrates are not limited to synapsin but are found on additional glycoproteins involved in modulating neuronal architecture. Together, our studies identify important roles for Fucalpha(1-2)Gal sugars in the regulation of neuronal proteins and morphological changes that may underlie synaptic plasticity.

Autocrine loops as a regulatory mechanism of estrogen action in rat hippocampus

In a previous study we have shown that synaptic plasticity in rat hippocampus is regulated by hippocampus-derived estradiol in a paracrine manner. Here, we ask whether this paracrine regulation is related to specific hippocampal regions, suggesting autocrine loops. To this end we studied the expression of stereogenic acute regulatory protein (StAR) and aromatase in tissue sections. Immunohistochemistry followed by semiquantitative image analysis revealed a three- fold higher expression of StAR and aromatase in neurons of the CA3 than of the CA1 region and in granule cells. Next, we reduced hippocampal estrogen synthesis in vitro with letrozole, an aromatase inhibitor. Letrozole treatment resulted in a dose-dependent decrease of 17β-estradiol in the medium of hippcampal slice cultures and in a dose-dependent downregulation of synaptic protein expression in hippocampal dispersion cultures. In hippocampal slice cultures spinophilin and synaptophysin are downregulated in a region-specific manner. The downregulation of both proteins was significantly higher in CA1 neurons and in granule cells, than in the CA3 region of the same slice. Our results strongly suggest independent autocrine loops in the regulation of synaptic proteins by hippocampus-derived estradiol and point to distinct functions of locally synthesized estradiol in closely defined hippocampal areas. Support contributed by the DFG.