Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase‐1, C/EBP‐β and ILAD‐1, a novel gene with homology to arrestins

Abstract

We recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression patterns of a new collection of three genes increased in expression by acute LSD administration. These genes were identified through additional screens of Affymetrix DNA microarrays and examined in experiments to assess dose-response, time course and the receptor mediating the expression changes. The first induced gene, C/EBP-b, is a transcription factor. The second gene, MKP-1, suggests that LSD activates the MAP (mitogen activated protein) kinase pathway. The third gene, ILAD-1, demonstrates sequence similarity to the arrestins. The increase in expression of each gene was partially mediated through LSD interactions at 5-HT 2A (serotonin) receptors. There is evidence of alternative splicing at the ILAD-1 locus. Furthermore, data suggests that various splice isoforms of ILAD-1 respond differently at the transcriptional level to LSD. The genes thus far found to be responsive to LSD are beginning to give a more complete picture of the complex intracellular events initiated by hallucinogens.

Psychedelics

“…For example, Ania3 is a splice variant within the Homer1 gene family that encodes synaptic proteins, and Ania3 has been implicated in metabotropic glutamate receptor (mGluR)-mediated plasticity. C/EBP-b is known to affect memory consolidation and synaptic strength; Ikb-a inhibits nuclear factor kB, which is important in synapse regulation; nor1 is a member of the Nr4a family of activity-dependent transcription factors, demonstrated to be important for transcriptiondependent LTP in the hippocampus; and sgk plays a role in long-term memory and the expression of LTP in hippocampal neurons (see references in Nichols and Sanders-Bush, 2004). The way in which these genes contribute to downstream transcriptional, structural, and functional sequelae of neuronal activation, however, remains poorly understood.…”

C/EBPβ and C/EBPδ transcription factors: Basic biology and roles in the CNS

“…Thus, C/EBPβ levels are increased in rat cerebellum by hypothyroidism (Alvarez et al 2005), in the hippocampus by experimental diabetes (Kazkayasi et al 2013), in rat frontal cortex and midbrain by systemic lysergic acid diethylamide injection (Nichols and Sanders-Bush 2004) and in rat hypothalamic neurons by dehydrationinduced remodeling (Qiu et al 2007). Down-regulation of C/EBPβ in the CNS is rarer and it has been reported in mouse in prefrontal cortex after inflammatory pain by facial carrageenan injection (Poh et al 2011) and in hippocampus after chronic electroconvulsive seizures (Chen et al 2004b).…”

The Interaction of Thioredoxin with Txnip

“…The homologs have been assigned official gene names arrestin domain-containing (Arrdc) 1 through 5. Three have so far been cloned and briefly characterized: human Arrdc4 as "down-regulated in hepatocellular carcinoma 1 (DRH1)" (37), rat Arrdc2 as "induced by lysergic acid diethylamide-1 (ILAD-1)" (38), and most recently, human Arrdc3 as "thioredoxin-binding-protein-2-like inducible membrane protein (TLIMP)" (39). The most distantly related protein, Arrdc5, is notable for its sperm-specific expression.…”