Characterization of a population of neural progenitor cells in the infant hippocampus

Paine, Simon; Willsher, Alex R.; Nicholson, Sarah Leigh; Sebire, Neil J.; Jacques, Thomas S.

doi:10.1111/nan.12065

Cited by 8 publications

(7 citation statements)

References 33 publications

(54 reference statements)

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“…We confirmed MCM2-positive cells in both patient groups which were morphologically similar to DCX-positive cells in the dentate gyrus. Similar DCX-positive cells have been recently described in the infant dentate gyrus (Paine et al 2013) but such immature-appearing DCX-positive cells have not previously been reported in the adult human hippocampus or in HS (D'Alessio et al 2010). There were, however, no group differences in the numbers of DCX or MCM2 cells to suggest altered dentate maturation or neurogenesis in HS-P relative to HS-NP patients.…”

Section: Discussionsupporting

confidence: 81%

Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

et al. 2014

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Section: Discussionsupporting

confidence: 81%

Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

et al. 2014

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“…DCX + stellate cells have been reported in the vicinity of acute infarcts with co-expression of astroglial lineage markers (GFAP, S100) rather than microglial or mature neuronal markers as NeuN [ 25 ]. In another study however, DCX + ‘rod’ cells in the infant hippocampal subgranular zone region, that morphologically resembled microglia, lacked CD68 and HLADR expression and were argued to represent neural progenitor cell types [ 34 ]. In adult mammals, DCX + cells are reported to be enriched in the subgranular zone of the hippocampus, and are described as ‘ramified’, although exhibiting more overt neuronal morphology with apical dendrites [ 14 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…We trialed four DCX commercially-available antibodies on selected surgical and PM cases. All four antibodies were previously validated in publications on human tissues [ 9 , 28 , 34 , 40 , 46 ] (Table 2 ; DCX Ab1 to 4). All DCX antibodies showed immunopositive labelling, but DCX Ab1 (clone 4604, Cell signaling, Boston, USA) labelled a greater diversity of cell types, and more intense labelling was observed in both surgical and PM human brain tissues.…”

Section: Methodsmentioning

confidence: 99%

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Doublecortin-expressing cell types in temporal lobe epilepsy

Liu

Matarı́n²,

Reeves

et al. 2018

acta neuropathol commun

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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.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0566-5) contains supplementary material, which is available to authorized users.

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“…To date, the study of microglia in the CNS of the human infant (1–12months) has been limited to a few regions, including the hippocampus ( Del Bigio and Becker, 1994 ; Kinney et al., 2015 ; Paine et al., 2014 ), caudate nucleus and medulla ( Esiri et al., 1991 ), cerebellum ( Maslinska et al., 1998 ), parietal cortex ( Billiards et al., 2006 ), other regions of the neocortex ( Kjær et al., 2016 ), and subcortical white matter and key white matter tracts ( Sigaard et al., 2014 ). While these studies identified unique microglial populations in discrete brain regions, they did not compare microglial populations, microglial morphology or activation state in multiple brain regions in the same subject.…”

Section: Introductionmentioning

confidence: 99%

Microglia in the human infant brain and factors that affect expression

Ambrose

Rodriguez

Waters

et al. 2020

Brain, Behavior, & Immunity - Health

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The present study reports on the microglial populations present in 34 regions of the human infant brain (1–11 months), and whether developmental parameters or extrinsic factors such as cigarette smoke exposure, prone sleeping and an upper respiratory tract infection (URTI) influence their expression. Further, we compare microglia populations amongst three sudden unexpected death in infancy (SUDI) sub-groups: explained SUDI (eSUDI, n = 7), sudden infant death syndrome (SIDS) I (n = 8) and SIDS II (n = 13). Ionised calcium binding adaptor molecule-1 (Iba1) was used to determine the morphology and area covered by microglia in a given brain region. Activation was explored using cluster-of-differentiation factor 68 (CD68) and human leukocyte antigen-DP,DQ,DR (HLA). We found regional heterogeneity in the area covered and activation status of microglia across the infant brain. The hippocampus, basal ganglia, white matter and dentate nucleus of the cerebellum showed larger areas of Iba1, while the brainstem had the smallest. Microglia in regions of the basal ganglia and cortex demonstrated positive correlations with infant developmental parameters, while in nuclei of the rostral medulla, negative correlations between microglia parameters were seen. URTI and cigarette smoke exposure were associated with a reduced microglial area in regions of the hippocampus and cortex (parietal and occipital), respectively. In the context of SIDS, a reduced microglial area was seen in SIDS II and fewer SIDS I infants demonstrated activated phenotypes in the hippocampus. Overall, we identify the distribution of microglia in the infant brain to be heterogenous, and influenced by intrinsic and extrinsic factors, and that the SIDS I group is a useful control group for future research into other infant CNS pathologies.

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Characterization of a population of neural progenitor cells in the infant hippocampus

Cited by 8 publications

References 33 publications

Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

Doublecortin-expressing cell types in temporal lobe epilepsy

Microglia in the human infant brain and factors that affect expression

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