Intra-day variations of blood reelin levels in healthy individuals

Abstract

Introduction: Reelin (RELN) is an extracellular glycoprotein best known to be crucial for neuronal migration during the embryonic period and regulation of synaptic plasticity in the adult brain, with recent studies pointing to reelin playing an important part in the organization of peripheral organs as well. Abnormalities in RELN function are associated with a variety of medical conditions in human beings. These alterations partly also reflect in RELN's blood levels, which gives it a clinical relevance as a potential biomarker. Requirement for a possible clinical use is a profound understanding of RELN's physiology. We hypothesized blood RELN levels could underlie time-dependent variations and therefore examined individuals' serum reelin concentrations in the course of one day. Material and methods: We obtained blood samples from healthy individuals (n = 10) at several times of measurement over a time period of 24 h. We subsequently determined the respective serum RELN concentrations utilizing an enzyme-linked immunosorbent assay and tested for intra-and interindividual variations in serum RELN concentrations over time. Results: All tested individuals' serum RELN levels displayed significant intraindividual variations in the course of 24 h. Test subjects' reelin day profiles showed substantial divergence among each other. Conclusions: Our findings point to short-term fluctuations in blood RELN levels being part of physiological RELN homeostasis. This is of special interest with regard to a potential clinical use of RELN as a biomarker.

Disease-Specific Changes in Reelin Protein and mRNA in Neurodegenerative Diseases

“…Furthermore, available Reelin ELISA Kits are useful for plasma-derived samples (i.e., [69,70]) but not in CSF or postmortem brains. In addition, a recent study demonstrates that Reelin levels displayed significant intraindividual variation in the course of 24 h in the plasma in healthy individuals [71]. As previously noted, the plasma level of Reelin are largely conditioned by liver production and show relevant changes in some liver-associated diseases [72][73][74][75].…”

Reelin Signaling and Synaptic Plasticity in Schizophrenia

“…Post-mortem examinations have revealed a decrease in reelin expression within the central nervous system (CNS) among affected individuals, a trend also observed in vivo [26][27][28]. Intriguingly, schizophrenic patients exhibited significantly elevated serum levels of major reelin isoforms [29]. Furthermore, alterations in the activity of reelin-specific receptors, such as very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (Apo-ER2), were noted during antipsychotic treatment [30][31][32].…”

“…Reports indicate reelin's potential role in schizophrenia development, possibly due to its impact on the laminar structure of the cortex and synaptic signaling, which in turn would result in changes in the expression of reelin in the CNS and serum as well as changes in the expression of its receptors during treatment [26][27][28][29][30][31][32]45]. Currently, systematic research is needed to link the clinical effects of treatment with changes in the reelin signaling pathway as the primary target of antipsychotic therapy.…”

“…Since reelin is a secreted extracellular matrix protein, measurements of its serum isoforms have been performed for various psychiatric disorders, including schizophrenia [29]. The serum levels of reelin 410 kDa and 330 kDa, but not 180 kDa, were significantly increased in schizophrenic patients, contrary to bipolar and unipolar mood disorders vs. normal controls [29]. Regarding the 410 kDa fragment, only the results in schizophrenic patients were significantly different (increased) vs. the control group.…”

The Alzheimer risk factor CD2AP causes dysfunction of the brain vascular network

“…Reelin is well characterized for its role in synaptic plasticity in the mature brain [71][72][73][74][75] , and promotes angiogenesis in the developing brain 76 . Interestingly, the glycoprotein is secreted from liver stellate cells into the bloodstream 77,78 and expressed in BECs 79 . However, the role of Reelin in the adult brain vasculature remains unknown.…”