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== Factors affecting reelin expression == [[File:Differential reelin levels in the cortex of adult high and low LG rats.gif|thumb|330px|Increased cortical reelin expression in the pups of "High LG" (licking and grooming) rats. A figure from Smit-Righter et al., 2009<ref name="pmid19357777" />]] 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.<ref name="pmid15066269" /> On a higher level, increased maternal care was found to correlate with reelin expression in rat pups; such correlation was reported in hippocampus<ref name="pmid16484373" /> and in the cortex.<ref name="pmid19357777" /> 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 [[Clinical depression|depression]].<ref name="pmid19477232" /> 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.<ref name="pmid19952965" /> ===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.<ref>{{cite journal | vauthors = Ishii K, Kubo KI, Nakajima K | title = Reelin and Neuropsychiatric Disorders | journal = Frontiers in Cellular Neuroscience | volume = 10 | pages = 229 | date = 2016-10-18 | pmid = 27803648 | pmc = 5067484 | doi = 10.3389/fncel.2016.00229 | doi-access = free }}</ref> 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.<ref name="pmid18757738" /> [[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.{{citation needed|date=January 2016}} 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 injection]]s of the following drugs:<ref name="Reelin_book_2008" /> {| class="wikitable" style="text-align:center" |- ! style="width:125px;"| Reelin expression ! style="width:85px;"| [[Clozapine]] ! style="width:85px;"| [[Fluoxetine]] ! style="width:85px;"| [[Haloperidol]] ! style="width:85px;"| [[Lithium (medication)|Lithium]] ! style="width:85px;"| [[Olanzapine]] ! style="width:85px;"| [[Valproic Acid]] |- | protein || '''β''' || '''β''' || '''β''' || '''β''' || '''β''' || '''β''' |- | mRNA || '''β''' || '''β''' || '''β''' || '''β''' || '''β''' || '''β''' |} 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]].<ref name="pmid19359144" />
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