Dataset Information

RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

ABSTRACT: Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types.

SUBMITTER: Camacho J

PROVIDER: S-EPMC4324637 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

Camacho Jasmin J Ejaz Ehsan E Ariza Jeanelle J Noctor Stephen C SC Martínez-Cerdeño Verónica V

Neuroscience letters 20140725

Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in lay ...[more]

PMID: 25067827

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Project description:Doublecortin (DCX) is widely regarded as a marker of immature and migrating neurons during development. While DCX expression persists in adults, particularly in the temporal lobe and neurogenic regions, it is unknown how seizures influence its expression. The aim of the present study was to explore the distribution and characteristics of DCX-expressing cells in surgical and postmortem samples from 40 adult and paediatric patients, with epilepsy and with or without hippocampal sclerosis (HS), compared to post mortem controls. The hippocampus (pes and body), parahippocampal gyrus, amygdala, temporal pole and temporal cortex were examined with DCX immunohistochemistry using four commercially-available DCX antibodies, labelled cells were quantified in different regions of interest as well as their co-expression with cell type specific markers (CD68, Iba1, GFAP, GFAP∂, nestin, SOX2, CD34, OLIG2, PDGFRβ, NeuN) and cell cycle marker (MCM2). Histological findings were compared with clinical data, as well as gene expression data obtained from the temporal cortex of 83 temporal lobe epilepsy cases with HS. DCX immunohistochemistry identified immature (Nestin-/NeuN-) neurons in layer II of the temporal neocortex in patients with and without epilepsy. Their number declined significantly with age but was not associated with the presence of hippocampal sclerosis, seizure semiology or memory dysfunction. DCX+ cells were prominent in the paralaminar nuclei and periamygdalar cortex and these declined with age but were not significantly associated with epilepsy history. DCX expressing cells with ramified processes were prominent in all regions, particularly in the hippocampal subgranular zone, where significantly increased numbers were observed in epilepsy samples compared to controls. DCX ramified cells co-expressed Iba1, CD68 and PDGFRβ, and less frequently MCM2, OLIG2 and SOX2, but no co-localization was observed with CD34, nestin or GFAP/GFAP ∂. Gene expression data from neocortical samples in patients with TLE and HS supported ongoing DCX expression in adults. We conclude that DCX identifies a range of morphological cell types in temporal lobe epilepsy, including immature populations, glial and microglial cell types. Their clinical relevance and biological function requires further study but we show some evidence for alteration with age and in epilepsy.

Project description:The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes' auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of 'associative' regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, we used a novel diffusion tensor imaging (DTI) sequence in archival post-mortem brains of a common dolphin (Delphinus delphis) and a pantropical dolphin (Stenella attenuata) to map their sensory and motor systems. Using thalamic parcellation based on traditionally defined regions for the primary visual (V1) and auditory cortex (A1), we found distinct regions of the thalamus connected to V1 and A1. But in addition to suprasylvian-A1, we report here, for the first time, the auditory cortex also exists in the temporal lobe, in a region near cetacean-A2 and possibly analogous to the primary auditory cortex in related terrestrial mammals (Artiodactyla). Using probabilistic tract tracing, we found a direct pathway from the inferior colliculus to the medial geniculate nucleus to the temporal lobe near the sylvian fissure. Our results demonstrate the feasibility of post-mortem DTI in archival specimens to answer basic questions in comparative neurobiology in a way that has not previously been possible and shows a link between the cetacean auditory system and those of terrestrial mammals. Given that fresh cetacean specimens are relatively rare, the ability to measure connectivity in archival specimens opens up a plethora of possibilities for investigating neuroanatomy in cetaceans and other species.

Project description:Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there were decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged amounts of 5hmC present in these regions, suggests the possibility that DNMT1 interacts with and alters MECP2 binding properties to selected promoters. Comparisons between data obtained from the FC with CB studies showed some common themes between brain regions which are discussed.

Dataset Information

RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

Publications

RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

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