Study | Methods | Age | Tissue | Markers | Main results | Tissue processing |
---|---|---|---|---|---|---|
Eriksson et al., 1998 | IHC | 67-72 yr | Postmortem | BrdU, calbindin, NSE, GFAP, NeuN | Incorporation of BrdU into the adult human DG | 4% PFA for 24 h, sliding microtome sectioning |
Blümcke et al., 2001 | IHC | 4 GW-46 yr | Biopsy (epilepsy and controls) and postmortem (controls) | Nestin, vimentin, Tuj1, Ki67, MAP1b/5, MAP2a-d, NF-L, NeuN, S100β, GFAP, calbindin, CD68, CD45 | Increased number of Nestin+ and Ki67+ cells in epileptic patients | 4% PFA for 24 h (biopsy) or formalin for > 2 w (autopsies); vibratome sectioning |
Jin et al., 2004 | IHC, WB | 13-90 yr | Postmortem | DCX, PSA-NCAM, TUC4, NeuroD1 | Increased expression levels of markers of immature neurons in AD patients measured by means of WB | Frozen samples (WB), or PFA 4% (unknown fixation time) plus embedding in paraffin |
Boekhoorn et al., 2006 | IHC | 63-70 yr (controls), 63-69 yr (AD) | Postmortem | DCX, Ki67, GFAP | Unaltered AHN in presenile AD cases | 10% formalin for 30-646 d; microtome sectioning |
Manganas et al., 2007 | Functional magnetic spectroscopy | — | Living humans | — | Identification of NSCs in the adult human hippocampus | NA |
Monje et al., 2007 | IHC | 10 mo-63 yr (controls), 10 mo-61 yr (Cancer) | Postmortem | DCX, Ki67, Olig2, CD68, CD20, CD3 | AHN is abolished by cancer treatment | Undisclosed fixation protocol and duration; embedding in paraffin |
Liu et al., 2008 | IHC, WB, RT-PCR | 18-78 yr (controls), 13-57 yr (epilepsy) | Biopsy (epilepsy) and postmortem (controls) | DCX, PCNA, MCM2, PSA-NCAM,Tuj1, NeuN, Reelin, calretinin, calbindin | Increased AHN in epilepsy | Perfusion/immersion in 15% formalin (following Waldvogel et al., 2006) |
Boldrini et al., 2009 | IHC | 17-53 yr (controls), 34-62 yr (MDD), 24-61 yr (MDDT-SSRI), 28-61 yr (MDDT-TCA) | Postmortem | Nestin, Ki67, NeuN, GFAP | Decreased number of progenitor cells with age; increased number of progenitor cells in females; antidepressant treatment increased the number of progenitor cells | Frozen tissue, fixed in 4% PFA for 1 wk and freezing |
Mattiesen et al., 2009 | IHC | 35-81 yr (controls), 35-85 yr (HIE) | Postmortem | TUC-4, calretinin, PCNA | Increased AHN and apoptosis after hypoxic-ischemic encephalopathy | Formalin fixation (undisclosed time and concentration) and embedding in paraffin |
Geha et al., 2010 | IHC | 22-35 yr (epileptic), 25-66 yr (control) | Biopsy (epilepsy and controls) and postmortem (controls) | Ki67, MCM2, Tuj1, MAP2, NeuN, calretinin, GFAP, Nestin, vimentin | Fixation affects cycle-related immunostaining; persistence of cycling cells in the adult SGZ; these cells were more abundant in epileptic patients | Formalin-zinc (formol 5%; zinc 3 g/L; sodium chloride 8 g/L) for 3 mo (postmortem) or 16 h (surgical), and embedding in paraffin |
Lucassen et al., 2010 | IHC | 45-85 yr | Postmortem | MCM2, PH3 | Reduction in the number of MCM2+ cells in depressed patients | 4% formaldehyde for 4-5 wk, and embedding in paraffin |
Knoth et al., 2010 | IHC, ISH, WB | 11 GW-100 yr | Postmortem | DCX, PCNA, Ki67, MCM2, Sox2, Nestin, TUC4, Tuj1, Prox1, PSA-NCAM, NeuroD1, GFAP, calretinin, NeuN | Murine features of human AHN; mild decrease of AHN with age | Formalin fixation (undisclosed fixation protocol) embedding in paraffin |
Crews et al., 2010 | IHC, qRT-PCR | 87 ± 4.6 yr (controls), 86.1 ± 1.7 yr (early/moderate AD), 80 ± 1.9 yr (severe AD) | Postmortem | DCX, Sox2 | Reduction in the number of DCX+ and Sox2+ cells in patients with AD | 4% PFA (undisclosed duration); vibratome sectioning |
D'Alessio et al., 2010 | IHC | 40.1 ± 6 yr (epileptic), 45.8 ± 14 yr (controls) | Biopsy (epilepsy) and postmortem (controls) | DCX | Reduced number of DCX+ cells in patients with epilepsy | Formalin for 5 d (undisclosed concentration), and embedding in paraffin; microtome sectioning |
Johnson et al., 2011 | IHC | 71-101 yr (controls), 75-87 yr (LBD) | Postmortem | PCNA, DCX, GFAP, Musashi | Decrease in the number of Musashi+ and increase in the number of DCX+ cells in the GCL in patients with Lewy body dementia | Undisclosed fixation protocol; embedding in paraffin; microtome sectioning |
Perry et al., 2012 | IHC | 81.2 ± 7 yr (AD), 80.9 ± 8.5 yr (controls) | Postmortem | Musashi, Nestin, PSA-NCAM, DCX, Tuj1 | Reduced numbers of Musashi+ cells, increased numbers of Nestin+ and PSA-NCAM+ cells, and unchanged numbers of DCX+ and Tuj1+ cells in patients with AD; the expression of DCX was specifically increased in the GCL | 4% formaldehyde for 4 wk and embedding in paraffin; microtome sectioning |
Boldrini et al., 2012 | IHC | 41.8 ± 14.6 yr (Control), 43.6 ± 13.3 yr (MD), 38.8 ± 13.8 yr (MD-SSRI), 43.2 ± 17.1 yr (MD-TCA) | Postmortem | Ki67, Nestin | Decreased number of Nestin+ cells with age; SSRI increased the number of Nestin+ cells in the DG of depressed patients | 4% formaldehyde (undisclosed duration) and freezing; freezing microtome sectioning |
Epp et al., 2013 | IHC | 46.8 ± 3.49 yr (Control), 42.83 ± 2.92 yr (MD), 41.5 ± 3.47 yr (MD-Psy) | Postmortem | DCX, p21, NeuN | Increased number of DCX+ cells in depressed patients | Frozen tissue, fixed for 15 min in 4% formaldehyde |
Spalding et al., 2013 | 14C dating, IHC | 19-92 yr | Postmortem | — | Mild decrease in the AHN rate with aging | Frozen tissue; undisclosed fixation protocol |
Gómez-Nicola et al., 2014 | IHC | 20-34 yr (Creutzfeldt-Jakob), 58-76 yr (AD), 20-35 yr or 58-79 yr (controls) | Postmortem | Ki67, Sox2, calretinin | Increased number of Ki67+ and calretinin+ cells in patients with Creutzfeldt-Jakob and ADs; decrease in these cell populations in aged controls | Formalin fixation (undisclosed fixation protocol) and embedding in paraffin |
D'Alessio et al., 2015 | IHC | 22-60 yr (controls), 22-51 yr (TLE) | Biopsy (epilepsy) and postmortem (controls) | Nestin | Reduced number of Nestin+ cells in patients with epilepsy | Formalin (undisclosed concentration) for 5 d, and embedding in paraffin; microtome sectioning |
Bayer et al., 2015 | IHC | 17-45 yr | Postmortem | Musashi, Nestin, Ki67, calretinin, GFAP, NeuN, Tuj1, DCX | Reduced number of Musashi+ and Nestin+ progenitor and proliferating cells in heroin-addict patients | 4% formaldehyde for 48 h-5 yr and embedding in paraffin; microtome sectioning |
Dennis et al., 2016 | IHC | 0.2-59 yr | Postmortem | Ki67, DCX, Tuj1, Olig2, EGFR, GFAP, PCNA | Marked decrease in proliferation with age; only microglial cells were identified among the proliferating cell population | 15%-20% formalin for 2-3 wk, and embedding in paraffin |
Allen et al., 2016 | IHC | 21-81 yr (controls), 55–75 yr (schizophrenia) | Postmortem | Ki67, NeuN | Reduced number of Ki67+ cells in patients with schizophrenia | Undisclosed fixation protocol |
Le Maître et al, 2018 | IHC | 24-78 yr | Postmortem | NeuN, DCX, Sox2, Ki67 | Reduction in AHN markers in alcohol addicts | Flash-frozen tissue, fixed in 4% formaldehyde for 15-30 min |
Mathews et al., 2017 | qPCR, IHC | 18-88 yr | Postmortem | Ki67, DCX, GFAP, Tbr2 | Reduced mRNA expression of DCX and Ki67 with aging | Frozen tissue (qPCR); fixation in formalin (undisclosed fixation protocol) and embedding in paraffin (IHC) |
Liu et al., 2018 | IHC | 12 GW-76 yr | Biopsy (epilepsy) and postmortem (epilepsy and controls) | Nestin, DCX, Mushashi, Tuj1, NeuN, GFAP, MAP2, Olig2, MCM2 | Increased densities of Nestin+ cells in patients with epilepsy | Formalin fixation (undisclosed fixation protocol) and embedding in paraffin |
Cipriani et al., 2018 | IHC | 13 GW-72 yr (controls), 74-89 yr (AD) | Postmortem | Nestin, GFAP, DCX, Ki67, MCM2, Sox2, Pax6, Tbr2, vimentin, Tuj1 | Sharp reduction of radial glia-like, proliferative, and DCX+ cells in the adult human DG | Frozen tissue was fixed in 4% PFA (undisclosed duration); other tissues were fixed in formalin (undisclosed duration) embedded in paraffin |
Sorrells et al., 2018 | IHC, EM | 14 GW-77 yr | Biopsy (epilepsy) and postmortem (controls) | Ascl1, BLBP, DCX, BrdU, GFAP, Hopx, Ki67, MCM2, Nestin, NeuN, NeuroD, Olig2, Pax6, Prox1, PSA-NCAM, Sox1, Sox2, Tbr2, Tuj1, vimentin | Absence of AHN markers in the adult human DG | Perfusion with 4% PFA, immersion in either 4% PFA or 10% formalin (undisclosed duration); additional fixation in 4% PFA for 2 d |
Boldrini et al., 2018 | IHC | 14-79 yr | Postmortem | PSA-NCAM, Sox2, Nestin, Ki67, DCX, NeuN, GFAP, BLBP | Preserved numbers of progenitor and immature cells throughout aging | Flash-frozen tissue, fixed in 4% PFA (undisclosed duration) |
Tartt et al., 2018 | IHC, RNAscope | 19-67 yr | Postmortem | DCX, NF, Sox2, PSA-NCAM, NeuN | Detection of AHN markers by means of RNAscope | Flash-frozen tissue and short fixation (undisclosed fixation protocol) |
Stepień et al., 2018 | IHC | 70 ± 6.03 yr (nonhemorragic stroke), 64.75 ± 12.23 yr (hemorrhagic), 64 ± 10.95 yr (controls) | Postmortem | GFAP, PH3 | Increased number of PH3+ cells in patients with hemorrhagic stroke | Undisclosed fixation method and embedding in paraffin; rotary microtome sectioning |
Moreno-Jiménez et al., 2019 | IHC | 43-97 yr | Postmortem | DCX, PH3, GFAP, Prox1, Tau, NeuN, calretinin, calbindin, Tuj1, PSA-NCAM | Persistence of AHN markers in neurologically healthy control subjects, mild decrease in AHN markers with aging, and sharp decrease in AD patients | 4% PFA for 24 h and vibratome sectioning |
Tobin et al., 2019 | IHC | 79-99 yr | Postmortem | DCX, PCNA, Nestin, Sox2, Ki67 | Persistence of AHN markers during aging and AD patients; correlation between AHN and cognitive scores | Undisclosed fixation method and embedding in paraffin |
Seki et al., 2019 | IHC | 9-49 yr | Biopsy | PSA-NCAM, Ki67, HuB, DCX | Reduced numbers of Ki67+/HuB+/DCX+ cells in the adult DG | 4% PFA for 3 d and freezing |
Flor-García et al., 2020 | IHC | 43-97 yr | Postmortem | DCX, NeuN, PSA-NCAM, MAP2, calbindin, Prox1, calretinin, PH3, GFAP, Tuj1, Tau | Reduced expression of NeuN in DCX+ compared with fully mature DGCs | 4% PFA for 24 h and vibratome sectioning |
↵aFor each study, the first author's last name, journal, year of publication, methodological approach, age of the subjects studied, type of samples, markers analyzed, main results obtained, and tissue processing protocol are indicated. As shown, most of these studies used postmortem human hippocampal samples and immunohistochemistry. PFA, Paraformaldehyde; IHC, Immunohistochemistry; ISH, in situ hydridization; RT-PCR, real time-polymerase chain reaction; qPCR, quantitative polymesare chain reaction; WB, Western blot; SGZ, subgranular zone; EM, electron microscopy; GCL, granule cell layer; GW, gestational week; MDD, major depression; MDDT-SSRI, MD patients treated with selective serotonin reuptake inhibitors; MDDT-TCA, MD patients treated with tricyclic antidepressants; MD-Psy, MD patients with psychotic symptoms; HIE, hypoxic-ischemic encephalopathy; LBD, Lewy body dementia; TLE, temporal lobe epilepsy; NSE, neuron-specific enolase; NeuN, neuronal nuclei; PCNA, proliferating cell nuclear antigen; MCM2, minichromosome maintenance complex component 2; Sox2, SRY (sex determining region Y)-box 2; Olig2, oligodendrocyte transcription factor; EGFR, epidermal growth factor receptor; Tbr2, T-box brain protein 2; Pax6, paired box protein 6; Ascl1, achaete-scute family BHLH transcription factor 1; BLBP, brain lipid-binding protein; NF-L, neurofilament light chains; PH3, phosphorylated histone 3; MAP2, microtubule-associated protein 2; and MAP1, microtubule-associated protein 1; NF, Neurofilament; NSE, Neuron-Specific Enolase; GFAP, Glial fibrillary acidic protein; DCX, Doublecortin; PSA-NCAM, Polysialylated-neural cell adhesion molecule; Prox1, Prospero homeobox protein 1; HuB; ELAV-like protein 2..