Bradykinin B2 receptor is essential to running-induced cell proliferation in the adult mouse hippocampus

Abstract

Physical exercise is a strong external effector that induces precursor cell proliferation in the adult mouse hippocampus. Research into mechanisms has focused on central changes within the hippocampus and we have established that serotonin is the signaling factor that transduces physical activity into adult neurogenesis. Less focus has been given on potential peripheral signals that may cause pro-mitotic running effects. Vasoactive kinin peptides are important for blood pressure regulation and inflammatory processes to maintain cardiovascular homeostasis. Acting via the two receptors termed B1 (B1R) and B2R, the peptides also function in the brain. In particular, studies attribute B2R a role in cell proliferation and differentiation into neurons in vitro. Here, we determined B1R and B2R mRNA expression levels in the adult mouse hippocampus and prefrontal cortex in vivo, and in response to running exercise. Using mice depleted in either or both receptors, B1-knockout (KO), B2KO and B1/2KO we observed changes in running performance overnight and in running distances. However, voluntary exercise led to the known pro-mitotic effect in the dentate gyrus of B1KO mice while it was attenuated in B2KO accompanied by an increase in microglia cells. Our data identify B2R as an important factor in running-induced precursor cell proliferation.

Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the RVM

“…Alternatively, exercise could enhance synaptogenesis of OFF cell projections in the spinal cord, purported to inhibit nociception, which would result in a lower proportion of ON-cells. In support, there is a substantial body of literature showing cell proliferation, increased synaptic densities, and synaptogenesis in the hippocampus after exercise [64][65][66]. For example, in the hippocampus, blockade of mu-opioid receptors reduces exercise-induced synaptogenesis suggesting endogenous opioids can promote synaptogenesis [47].…”

Kinin B1 receptor deficiency protects mice fed by cafeteria diet from abnormal glucose homeostasis

“…Those results point out to an inhibition of the gluconeogenesis, and were confirmed by the slightly increased AKT phosphorylation observed in the Western blot analysis, which is also consistent with the hyperinsulinemia caused by CAF. AKT phosphorylation is a central intracellular action caused by the insulin signaling [ 26 ]. Phosphorylated AKT phosphorylates FoxO1 cause its exclusion from the nucleus.…”

“…Specific primer sequences for the genes encoding glucose-6-phosphatase, glucokinase, phosphoenolpyruvate, carboxykinase, fructose 1,6-bisphosphatase, and hepatocyte nuclear factor 4-alpha were designed and tested in the samples by analyzing the curve patterns, in order to set the amplification effectiveness of each primer pair. For the Kinin B2 receptor expression Quantitative PCR was performed with the TaqMan system (Applied Biosystems, Carlsbad, CA) and specific kit of oligonucleotides (B2R-Forward- , B2R-Reverse- , the control gene was the Glyceraldehyde-3-phosphate dehydrogenase (GadDH)—Forward- and Reverse- ) [ 26 ], and the thermic protocol was as follows: holding 95°C for 10 min, and a cycle of 95°C for 30 s, 60°C for 30 s, and 72°C for 30 s repeated 40 times. Gene expression was normalized against the GadDH gene expression and defined as relative values utilizing the threshold cycle method (CT; 2-ΔΔCt), following instructions from the manufacturer [ 27 ].…”

Long‐term environmental enrichment reduces microglia morphological diversity of the molecular layer of dentate gyrus

“…Many studies have shown that environmental enrichment including voluntary exercise and somatomotor and visuospatial stimulation is capable of promoting the modulation of cytokines (Pedersen, 2009) and chemokines (Trøseid et al, 2004), natural killer cells (Benaroya‐Milshtein et al, 2004), and T lymphocytes mobilization (Marashi, Barnekow, Ossendorf, & Sachser, 2003; de Sousa et al, 2011; Singhal et al, 2020), microglia (Gomes et al., 2019; de Sousa et al., 2015) and astrocytes numerical and morphological changes (Diniz et al, 2010; Diniz, Silva, et al, 2016; Leardini‐Tristão et al, 2020; Singhal et al, 2020) and neurogenesis (Valero, Paris, & Sierra, 2016; Wasinski, Batista, Bader, Araujo, & Klempin, 2018). Bi‐directional cross talk between microglia, astrocytes and neurons (Singhal et al, 2020; Kofuji & Araque, 2020) are key elements to achieve homeostatic conditions, and chemokine signaling seems to be essential to orchestrate communication among them, preserving brain function (Trettel, Di Castro, & Limatola, 2019).…”