Gene expression profiles in microdissected neurons from human hippocampal subregions

Torres-Muñoz, Jorge; Waveren, Corina van; Keegan, Martha G; Bookman, Richard J.; Petito, Carol K.

doi:10.1016/j.molbrainres.2004.05.017

Cited by 53 publications

(29 citation statements)

References 71 publications

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“…In another study investigating differential expression between CA1 and CA3 neurons in human postmortem brain, surprisingly few differences in gene expression were identified. Using a cDNA microarray representing over 10,000 genes and unknown ESTs, less than 1% of the genes displayed differential expression, which is considerably lower than all the studies so far, be it in rodents, the marmoset monkey or human hippocampus (Datson et al, 2004;Lein et al, 2004;Torres-Munoz et al, 2004;Ginsberg and Che, 2005). Further studies in human brain investigating larger numbers of genes and including the dentate gyrus region are necessary to shed more light on the situation in the human hippocampus.…”

Section: Discussionmentioning

confidence: 83%

“…It has also been shown that within the same subregion molecular heterogeneity exists along the dorsal-ventral axis of the hippocampus (Leonardo et al, 2006). The studies investigating differences in hippocampal gene expression in human brain are sparse and have only focused on CA1 and CA3 (Torres-Munoz et al, 2004;Ginsberg and Che, 2005). However, this has so far never been investigated in the DG of a (nonhuman) primate.…”

Section: Introductionmentioning

confidence: 99%

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A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

Datson¹,

Morsink²,

Steenbergen³

et al. 2009

Hippocampus

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Recent studies in rodents have shown that there are significant differences in gene expression profiles between the hippocampal subregions CA1, CA3, and DG. These differences in molecular make-up within the hippocampus most likely underlie the differences in morphology, physiology, and vulnerability to insults that exist between the subregions of the hippocampus and are as such part of the basic molecular architecture of the hippocampus. The aim of this study was to investigate at large scale whether these subregional differences in gene expression are conserved in the hippocampus of a nonhuman primate, the common marmoset. This study is very timely, given the recent development of the first marmoset-specific DNA microarray, exclusively containing sequences targeting transcripts derived from the marmoset hippocampus. Hippocampal subregions CA1, CA3, and DG were isolated by laser microdissection and RNA was isolated, amplified, and hybridized to the marmoset-specific microarray (EUMAMA) containing more than 1,500 transcripts expressed in the adult marmoset hippocampus. Large differences in expression were observed in particular between the DG region and both pyramidal subregions. Moreover, the subregion-specific patterns of gene expression showed a remarkable conservation with the rodent brain both in terms of individual genes and degree of differential expression. To our knowledge, this is the first study investigating large scale hippocampal gene expression in a nonhuman primate. The obtained expression profiles not only provide novel data on the expression of more than 1,500 transcripts per hippocampal subregion but also are of potential interest to neuroscientists interested in the role of the different subregions in learning and memory in the nonhuman primate brain.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

Datson¹,

Morsink²,

Steenbergen³

et al. 2009

Hippocampus

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“…In addition, CCR2 expression in brain parenchyma is controversial. Studies using immunohistochemistry and autoradiography techniques demonstrated either constitutive or inducible expression of CCR2 both in neurons and astrocytes (Meucci et al, 1998;Zuurman et al, 2003;Torres-Muñoz et al, 2004;Rosténe et al, 2007), and several reports described physiological effects of CCL2 on synaptic transmission (Guyon et al, 2009;Zhou et al, 2011). However, recent analyses of CNS tissues of CCR2-RFP mice provided no evidence of CCR2 expression either on neurons, astrocytes, microglia, or oligodendrocytes (Saederup et al, 2010), apparently limiting CCR2 expression in the brain to pathological conditions with infiltration of Ly6C(hi) monocytes.…”

Section: Discussionmentioning

confidence: 99%

CXCL16 Orchestrates Adenosine A₃Receptor and MCP-1/CCL2 Activity to Protect Neurons from Excitotoxic Cell Death in the CNS

Rosito¹,

Deflorio²,

Limatola³

et al. 2012

J. Neurosci.

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A role for chemokines as molecules mediating neuron-glia cross talk has emerged in recent years, both in physiological and pathological conditions. We demonstrate here for the first time that the chemokine CXCL16 and its unique receptor CXCR6 are functionally expressed in the CNS, and induce neuroprotection against excitotoxic damage due to excessive glutamate (Glu) exposure and oxygen glucose deprivation (OGD). In mice and rats we found that, to exert neuroprotection, CXCL16 requires the presence of extracellular adenosine (ADO), and that pharmacological or genetic inactivation of the ADO A 3 receptor, A 3 R, prevents CXCL16 effect. In experiments with astrocytes cocultured with cxcr6 gfp/gfp hippocampal cells, we demonstrate that CXCL16 acts directly on astrocytes to release soluble factors that are essential to mediate neuroprotection. In particular, we report that (1) upon stimulation with CXCL16 astrocytes release monocyte chemoattractant protein-1/CCL2 and (2) the neuroprotective effect of CXCL16 is reduced in the presence of neutralizing CCL2 antibody. In conclusion, we found that chemokine CXCL16 is able to mediate cross talk between astrocytes and neighboring neurons and, in pathological conditions such as excessive Glu or OGD exposure, is able to counteract neuronal cell death through an ADO-dependent chemokine-induced chemokine-release mechanism.

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“…The physiological significance of this effect is unclear. In the adult hippocampus, CCR5 expression is mainly localized in neurons of the CA1 region and dentate gyrus (Torres-Munoz et al, 2004;Westmoreland et al, 2002) and within neural progenitor cells (Tran et al, 2007). Multipotent neural progenitor cells are still present in the adult hippocampus and are capable of giving rise to functional neurons and glial cells (Lledo et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain

et al. 2008

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Chemokine receptors, and in particular CXCR4 and CCR5 play a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV)4 associated dementia (HAD). Thus, new insight into the expression of CXCR4 in the central nervous system may help develop therapeutic compounds against HAD. Brain-derived neurotrophic factor (BDNF) is neuroprotective in vitro against two strains of the HIV envelope protein gp120 that binds to CXCR4 or CCR5. Therefore, we examined whether BDNF modulates chemokine receptor expression in vivo. The content of CXCR4 mRNA and proteins was determined in the cerebral cortex and hippocampus of 6-month-old BDNF heterozygous mice and wild type littermates by using polymerase chain reaction and immunohistochemistry, respectively. BDNF heterozygous mice exhibited an increase in CXCR4 mRNA compared to wild type. Histological analyses revealed an up-regulation of CXCR4 immunoreactivity mainly in neurons. Most of these neurons were positive for TrkB, the BDNF receptor with a tyrosine kinase activity. Increases in CXCR4 mRNA levels were observed in 18-month-old BDNF heterozygous mice but not in 7 day-old mice, suggesting that the modulatory role of BDNF occurs only in mature animals. To determine whether BDNF affects also CXCR4 internalization, SH-SY5Y neuroblastoma cells were exposed to BDNF and cell surface CXCR4 levels were measured at various times. BDNF induced CXCR4 internalization within minutes. Lastly, BDNF heterozygous mice showed higher levels of CCR5 and CXCR3 mRNA than wild type in the cerebral cortex, hippocampus and striatum. Our data indicate that BDNF may modulate the availability of chemokine receptors implicated in HIV infection.

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Gene expression profiles in microdissected neurons from human hippocampal subregions

Cited by 53 publications

References 71 publications

A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

CXCL16 Orchestrates Adenosine A₃Receptor and MCP-1/CCL2 Activity to Protect Neurons from Excitotoxic Cell Death in the CNS

Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain

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Gene expression profiles in microdissected neurons from human hippocampal subregions

Cited by 53 publications

References 71 publications

A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and DG is conserved in the brain of the common marmoset

CXCL16 Orchestrates Adenosine A3Receptor and MCP-1/CCL2 Activity to Protect Neurons from Excitotoxic Cell Death in the CNS

Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain

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Resources

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CXCL16 Orchestrates Adenosine A₃Receptor and MCP-1/CCL2 Activity to Protect Neurons from Excitotoxic Cell Death in the CNS