Endoplasmic Reticulum in Metaplasticity: From Information Processing to Synaptic Proteostasis.

The ER (endoplasmic reticulum) is a Ca2+ reservoir and the unique protein-synthesizing machinery which is distributed throughout the neuron and composed of multiple different structural domains. One such domain is called EMC (endoplasmic reticulum membrane protein complex), pleiotropic nature in cellular functions. The ER/EMC position inside the neurons unmasks its contribution to synaptic plasticity via regulating various cellular processes from protein synthesis to Ca2+ signaling. Since presynaptic Ca2+ channels and postsynaptic ionotropic receptors are organized into the nanodomains, thus ER can be a crucial player in establishing TMNCs (transsynaptic molecular nanocolumns) to shape efficient neural communications. This review hypothesized that ER is not only involved in stress-mediated neurodegeneration but also axon regrowth, remyelination, neurotransmitter switching, information processing, and regulation of pre- and post-synaptic functions. Thus ER might not only be a protein-synthesizing and quality control machinery but also orchestrates plasticity of plasticity (metaplasticity) within the neuron to execute higher-order brain functions and neural repair.

Nutritional, Phytochemical, and In Vitro Antioxidant Activity Analysis of Different States of Soy Products.

Consumer demand for food nutritional content and quality is driving the design of plant-based foods that are enhanced with proteins. In this study, we aimed to reveal the nutrient compositional differences of various states of soy flours. We compared soy protein concentrate (SPC) with full fat (FF), raw soy flour (RSF), and defatted (DF) soy flour for investigating nutritional content, phytochemicals, and in vitro antioxidant activity. The results showed that the SPC contained significantly (p < 0.001) higher protein content (65.14%) and low-fat content (0.54%) than RSF, FF, and DF. Furthermore, the findings revealed that all products contain a significant (ANOVA, p < 0.001) amount of essential minerals. The RSF contains significantly higher (p < 0.001) potassium (1178.6 mg), calcium (216.77 mg), and magnesium (247 mg) per 100 g than FF, DF, and SPC. SPC contains essential amino acids, but we were unable to detect phenylalanine and tryptophan due to a limitation in the method. Furthermore, using methanolic and aqueous extracts of RSF, FF, DF, and SPC, the flavonoid, phenolics, and antioxidant capacity were also evaluated. According to the findings, soy products in methanolic extract had higher phenolic (about 12-34 mg/g) and flavonoid (about 63-150 mg/g) levels than aqueous extract. Results also demonstrated that FF had higher phenolic content, and SPC had higher flavonoid content than the other products. In vitro models such as phosphomolybdenum blue, FRAP, DPPH, and ABTS assays were used to study the total antioxidant and free radical scavenging potential of soy products, and results found that soy products contained a significant (p < 0.001) amount of antioxidant equivalent to gallic acid and vitamin C standard. In the DPPH and ABTS assays, the results also showed that soy products can reduce free radicals in different in vitro models. Altogether, these findings suggest that soy flours, particularly DF and SPC, could be a beneficial food ingredient in the formulation of functional foods.

IGFBP-2 Signaling in the Brain: From Brain Development to Higher Order Brain Functions.

Insulin-like growth factor-binding protein-2 (IGFBP-2) is a pleiotropic polypeptide that functions as autocrine and/or paracrine growth factors. IGFBP-2 is the most abundant of the IGFBPs in the cerebrospinal fluid (CSF), and developing brain showed the highest expression of IGFBP-2. IGFBP-2 expressed in the hippocampus, cortex, olfactory lobes, cerebellum, and amygdala. IGFBP-2 mRNA expression is seen in meninges, blood vessels, and in small cell-body neurons (interneurons) and astrocytes. The expression pattern of IGFBP-2 is often developmentally regulated and cell-specific. Biological activities of IGFBP-2 which are independent of their abilities to bind to insulin-like growth factors (IGFs) are mediated by the heparin binding domain (HBD). To execute IGF-independent functions, some IGFBPs have shown to bind with their putative receptors or to translocate inside the cells. Thus, IGFBP-2 functions can be mediated both via insulin-like growth factor receptor-1 (IGF-IR) and independent of IGF-Rs. In this review, I suggest that IGFBP-2 is not only involved in the growth, development of the brain but also with the regulation of neuronal plasticity to modulate high-level cognitive operations such as spatial learning and memory and information processing. Hence, IGFBP-2 serves as a neurotrophic factor which acts via metaplastic signaling from embryonic to adult stages.

IGFBP2 Plays an Essential Role in Cognitive Development during Early Life.

Identifying the mechanisms underlying cognitive development in early life is a critical objective. The expression of insulin-like growth factor binding protein 2 (IGFBP2) in the hippocampus increases during neonatal development and is associated with learning and memory, but a causal connection has not been established. Here, it is reported that neurons and astrocytes expressing IGFBP2 are distributed throughout the hippocampus. IGFBP2 enhances excitatory inputs onto CA1 pyramidal neurons, facilitating intrinsic excitability and spike transmission, and regulates plasticity at excitatory synapses in a cell-type specific manner. It facilitates long-term potentiation (LTP) by enhancing N-methyl-d-aspartate (NMDA) receptor-dependent excitatory postsynaptic current (EPSC), and enhances neurite proliferation and elongation. Knockout of igfbp2 reduces the numbers of pyramidal cells and interneurons, impairs LTP and cognitive performance, and reduces tonic excitation of pyramidal neurons that are all rescued by IGFBP2. The results provide insight into the requirement for IGFBP2 in cognition in early life.