mice, delahaye et al. detected a significant upregulation of both reln and dab1 and speculated on possible protective effects of such over-expression. in 2020, a study reported a novel variant in reln gene (s2486g) which was associated with ankylosing spondylitis in a large family. this suggested a potential insight into the pathophysiological involvement of reelin via inflammation and osteogenesis pathways in ankylosing spondylitis, and it could broaden the horizon toward new therapeutic strategies. a 2020 study from ut southwestern medical center suggests circulating reelin levels might correlate with ms severity and stages, and that lowering reelin levels might be a novel way to treat ms. factors affecting reelin expression increased cortical reelin expression in the pups of "high lg" (licking and grooming) rats. a figure from smit-righter et al., 2009 the expression of reelin is controlled by a number of factors besides the sheer number of cajal-retzius cells. for example, tbr1 transcription factor regulates reln along with other t-element-containing genes. on a higher level, increased maternal care was found to correlate with reelin expression in rat pups; such correlation was reported in hippocampus and in the cortex. according to one report, prolonged exposure to corticosterone significantly decreased reelin expression in murine hippocampi, a finding possibly pertinent to the hypothetical role of corticosteroids in depression. one small postmortem study has found increased methylation of reln gene in the neocortex of persons past their puberty compared with those that had yet to enter the period of maturation. psychotropic medication as reelin is being implicated in a number of brain disorders and its expression is usually measured posthumously, assessing the possible medication effects is important. according to the epigenetic hypothesis, drugs that shift the balance in favour of demethylation have a potential to alleviate the proposed methylation-caused downregulation of reln and gad67. in one study, clozapine and sulpiride but not haloperidol and olanzapine were shown to increase the demethylation of both genes in mice pretreated with l-methionine. valproic acid, a histone deacetylase inhibitor, when taken in combination with antipsychotics, is proposed to have some benefits. but there are studies conflicting the main premise of the epigenetic hypothesis, and a study by fatemi et al. shows no increase in reln expression by valproic acid; that indicates the need for further investigation. fatemi et al. conducted the study in which reln mrna and reelin protein levels were measured in rat prefrontal cortex following a 21-day of intraperitoneal injections of the following drugs: reelin expression clozapine fluoxetine haloperidol lithium olanzapine valproic acid protein↓↔↓↓↑↔ mrna↑↑↓↑↑↓ in 2009, fatemi et al. published the more detailed work on rats using the same medication. here, cortical expression of several participants (vldlr, dab1, gsk3b) of the signaling chain was measured besides reelin itself, and also the expression of gad65 and gad67.