The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia

Targeting the Hippocampal Mossy Fiber Synapse for the Treatment of Psychiatric Disorders

“…Increased frequency of dentate granule cells with basal dendrites [149] Neurotransmitter receptor Glutamate Decrease in [ 3 H]kainate binding [115] Decreases in AMPA receptor subunit GluR1 and GluR2 mRNAs (no significant change in CA1) [116] Decrease in kainate receptor subunits GluR6 and KA2 mRNAs (no significant change in CA1) [117] Decrease in NMDAR receptor subunit NR1mRNAs (no significant change in CA1) [118,120] Acetylcholine Decrease in [ 125 l]-α-bungarotoxin (nicotinic ligand) binding (no significant change in CA1) [121] Decrease in [ 3 H]pirenzepine (muscarinic ligand) binding [122] GABA Increase in [ 3 H]muscimol (GABA A ligand) binding [113] Decrease in GABA B immunoreactive cells [119] Noradrenaline Decrease in [ 125 I]iodopindolol (βreceptor ligand) binding [114] Hormone receptor Decrease in glucocorticoid receptor mRNA [191] Decrease in estrogen receptor α mRNA (dentate gyrus-specific change) [192] Presynaptic protein Decrease in synaptophysin immunoreactivity (no significant change in CA1) [123] Increase in synaptophysin immunoreactivity [124] Decrease in SNAP-25 immunoreactivity [124] Neurodevelopment/Plasticity Decrease in PSA-NCAM immunoreactive cell in hilus [193] Decrease in [ 3 H]forskolin (adenylate cyclase ligand) binding (dentate gyrus-specific change) [194] Decrease in density of reelin immunoreactive cells [136] Increase in retinoic acid receptor α immunoreactive granule cells [138] Decrease in calbindin mRNA (laser captured dentate gyrus) [125] Decrease in reelin mRNA-expressing molecular layer cells [137] Decrease in cells with proliferation maker Ki-67 immunoreactivity…”

Dietary (n-3) Fatty Acids and Brain Development1

“…Together with its retinoic acid receptor (RAR), RXR play key roles in many aspects of development, including neurogenesis during embryogenesis, morphological differentiation of catecholaminergic neurons, and activity-dependent plasticity. RAR and RXR are also highly expressed in the hippocampus, which may be relevant to understanding the role DHA adult brain function (33,34). Further, several studies have provided evidence that (n-3) fatty acid deficiency alters the expression of genes involved in the control of synaptic plasticity, cytoskeleton and membrane assembly, as well as signal transduction and ion channel formation (35), many of which are downstream targets of RAR-RXR signaling.…”

Microarray results suggest altered transport and lowered synthesis of retinoic acid in schizophrenia

“…18 The hypothesis that dysregulated retinoid transport and function contributes to schizophrenia has recently received substantial additional immunohistochemical support with the discovery that expression of retinoic acid receptor alpha (RARA) protein is more than two-fold greater in the dentate gyrus in post-mortem schizophrenia brains compared to controls. 19 RAs and their analogues represent well-studied therapeutic targets in cancer and dermatology. Perusal of the literature from these fields indicates that retinoids modulate cell functioning through diverse mechanisms, including gene silencing and nuclear translocation, as well as through direct transcriptional activation.…”