The function of connective tissues depends on the physical and biochemical properties of their extracellular matrix (ECM), which are in turn dictated by ECM protein composition. With the primary objective of obtaining quantitative estimates for absolute and relative amounts of ECM proteins, we performed a systematic review of papers reporting protein composition of human connective tissues. Articles were included in meta-analysis if they contained absolute or relative quantification of proteins found in the ECM of human bone, adipose tissue, tendon, ligament, cartilage and skeletal muscle. We generated absolute quantitative estimates for collagen in articular cartilage, intervertebral disk (IVD), skeletal muscle, tendon, and adipose tissue. In addition, sulfated glycosaminoglycans were quantified in articular cartilage, tendon and skeletal muscle; total proteoglycans in IVD and articular cartilage, fibronectin in tendon, ligament and articular cartilage, and elastin in tendon and IVD cartilage. We identified significant increases in collagen content in the annulus fibrosus of degenerating IVD and osteoarthritic articular cartilage, and in elastin content in degenerating disc. In contrast, collagen content was decreased in the scoliotic IVD. Finally, we built quantitative whole-tissue component breakdowns. Quantitative estimates improve our understanding of composition of human connective tissues, providing insights into their function in physiology and pathology.
Stress-related psychiatric disorders including depression involve complex cellular and molecular changes in the brain, and GABAergic signaling dysfunction is increasingly implicated in the etiology of mood disorders. Parvalbumin (PV)-expressing neurons are fast-spiking interneurons that, among other roles, coordinate synchronous neuronal firing. Mounting evidence suggests that the PV neuron phenotype is altered by stress and in mood disorders. In this systematic review, we assessed PV interneuron alterations in psychiatric disorders as reported in human postmortem brain studies and animal models of environmental stress. This review aims to 1) comprehensively catalog evidence of PV cell function in mood disorders (humans) and stress models of mood disorders (animals); 2) analyze the strength of evidence of PV interneuron alterations in various brain regions in humans and rodents; 3) determine whether the modulating effect of antidepressant treatment, physical exercise, and environmental enrichment on stress in animals associates with particular effects on PV function; and 4) use this information to guide future research avenues. Its principal findings, derived mainly from rodent studies, are that stress-related changes in PV cells are only reported in a minority of studies, that positive findings are region-, age-, sex-, and stress recency-dependent, and that antidepressants protect from stress-induced apparent PV cell loss. These observations do not currently translate well to humans, although the postmortem literature on the topic remains limited.
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