Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood

AbstractIn the dentate gyrus of the rodent hippocampus, neurogenesis begins prenatally and continues to the end of life. Adult-born neurons often die in the first few weeks after mitosis, but then survive indefinitely. In contrast, neurons born at the peak of development are initially stable but can die later in adulthood. Physiological and pathological changes in hippocampal structure may therefore result from both the addition of new neurons and the loss of older neurons. However, it is unknown whether neurons born at other stages of development also undergo delayed cell death. Here, we used BrdU to label dentate granule cells that were born in rats on embryonic day 19 (E19; before the developmental peak), postnatal day 6 (P6; peak) and P21 (after the peak). We quantified BrdU+ neurons in separate groups of rats at 2 and 6 months post-BrdU injection. Consistent with previous work, there was a 15% loss of P6-born neurons between 2 and 6 months of age. In contrast, E19- or P21-born neurons were stable throughout young adulthood. Delayed death of P6-born neurons suggests they may play a unique role in hippocampal plasticity and pathology in adulthood.

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Isoflurane Prevents Delayed Cell Death in an Organotypic Slice Culture Model of Cerebral Ischemia

Anesthesiology ◽

10.1097/00000542-200201000-00033 ◽

2002 ◽

Vol 96 (1) ◽

pp. 189-195 ◽

Cited By ~ 52

Author(s):

Breandan L. Sullivan ◽

David Leu ◽

Donald M. Taylor ◽

Christian S. Fahlman ◽

Philip E. Bickler

Keyword(s):

Cell Death ◽

Cerebral Ischemia ◽

Dentate Gyrus ◽

Neuronal Death ◽

Slice Culture ◽

Mk 801 ◽

Organotypic Slice Culture ◽

Delayed Cell Death ◽

Culture Model

Background General anesthetics reduce neuronal death caused by focal cerebral ischemia in rodents and by in vitro ischemia in cultured neurons and brain slices. However, in intact animals, the protective effect may enhance neuronal survival for only several days after an ischemic injury, possibly because anesthetics prevent acute but not delayed cell death. To further understand the mechanisms and limitations of volatile anesthetic neuroprotection, the authors developed a rat hippocampal slice culture model of cerebral ischemia that permits assessment of death and survival of neurons for at least 2 weeks after simulated ischemia. Methods Survival of CA1, CA3, and dentate gyrus neurons in cultured hippocampal slices (organotypic slice culture) was examined 2-14 days after 45 min of combined oxygen-glucose deprivation at 37 degrees C (OGD). Delayed cell death was serially measured in each slice by quantifying the binding of propidium iodide to DNA with fluorescence microscopy. Results Neuronal death was greatest in the CA1 region, with maximal death occurring 3-5 days after OGD. In CA1, cell death was 80 +/- 18% (mean +/- SD) 3 days after OGD and was 80-100% after 1 week. Death of 70 +/- 16% of CA3 neurons and 48 +/- 28% of dentate gyrus neurons occurred by the third day after OGD. Both isoflurane (1%) and the N-methyl-D-aspartate antagonist MK-801 (10 microm) reduced cell death to levels similar to controls (no OGD) for 14 days after the injury. Isoflurane also reduced cell death in CA1 and CA3 caused by application of 100 but not 500 microm glutamate. Cellular viability (calcein fluorescence) and morphology were preserved in isoflurane-protected neurons. Conclusions In an in vitro model of simulated ischemia, 1% isoflurane is of similar potency to 10 microm MK-801 in preventing delayed cell death. Modulation of glutamate excitotoxicity may contribute to the protective mechanism.

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Intact memory for local and distal cues in male and female rats that lack adult neurogenesis

10.1101/304733 ◽

2018 ◽

Author(s):

Desiree R Seib ◽

Erin Chahley ◽

Oren Princz-Lebel ◽

Jason S Snyder

Keyword(s):

Dentate Gyrus ◽

Adult Neurogenesis ◽

Granule Cells ◽

Sensory Information ◽

Female Rats ◽

Male Rats ◽

Separation Function ◽

Male And Female ◽

Male And Female Rats ◽

Adult Born Neurons

ABSTRACTThe dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly-processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis.

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Faculty Opinions recommendation of Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1071727.529703 ◽

2007 ◽

Author(s):

Leonard Maler

Keyword(s):

Spatial Memory ◽

Dentate Gyrus ◽

Granule Cells ◽

Preferential Incorporation

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Early changes in synaptic and intrinsic properties of dentate gyrus granule cells in a mouse model of Alzheimer's disease neuropathology and atypical effects of the cholinergic antagonist atropine

Neurobiology of Disease ◽

10.1016/j.nbd.2021.105274 ◽

2021 ◽

Vol 152 ◽

pp. 105274

Author(s):

David Alcantara-Gonzalez ◽

Elissavet Chartampila ◽

Chiara Criscuolo ◽

Helen E. Scharfman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Dentate Gyrus ◽

Granule Cells ◽

Intrinsic Properties ◽

Cholinergic Antagonist ◽

Model Of Alzheimer’S Disease

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Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22063275 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3275

Author(s):

Andrea Tapia-Bustos ◽

Carolyne Lespay-Rebolledo ◽

Valentina Vío ◽

Ronald Pérez-Lobos ◽

Emmanuel Casanova-Ortiz ◽

...

Keyword(s):

Cell Death ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Perinatal Asphyxia ◽

Mrna Levels ◽

Protein Levels ◽

Delayed Cell Death ◽

External Capsule ◽

Stem Cell Treatment ◽

Main Effects

The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 μL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.

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Stroke promotes the development of brain atrophy and delayed cell death in hypertensive rats

Scientific Reports ◽

10.1038/s41598-020-75450-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mohammed A. Sayed ◽

Wael Eldahshan ◽

Mahmoud Abdelbary ◽

Bindu Pillai ◽

Waleed Althomali ◽

...

Keyword(s):

Cell Death ◽

Fold Increase ◽

Magnetic Resonance Images ◽

Protein Quantification ◽

Motor Deficits ◽

Long Term Memory ◽

Delayed Presentation ◽

Hypertensive Rats ◽

Post Stroke ◽

Delayed Cell Death

AbstractPost-stroke cognitive impairment (PSCI) is a major source of disability, affecting up to two thirds of stroke survivors with no available therapeutic options. The condition remains understudied in preclinical models due to its delayed presentation. Although hypertension is a leading risk factor for dementia, how ischemic stroke contributes to this neurodegenerative condition is unknown. In this study, we used a model of hypertension to study the development of PSCI and its mechanisms. Spontaneously hypertensive rats (SHR) were compared to normotensive rats and were subjected to 1-h middle cerebral artery occlusion or sham surgery. Novel object recognition, passive avoidance test and Morris water maze were used to assess cognition. In addition, brain magnetic resonance images were obtained 12-weeks post-stroke and tissue was collected for immunohistochemistry and protein quantification. Stroked animals developed impairment in long-term memory at 4-weeks post-stroke despite recovery from motor deficits, with hypertensive animals showing some symptoms of anhedonia. Stroked SHRs displayed grey matter atrophy and had a two-fold increase in apoptosis in the ischemic borderzone and increased markers of inflammatory cell death and DNA damage at 12 weeks post-stroke. This indicates that preexisting hypertension exacerbates the development of secondary neurodegeneration after stroke beyond its acute effects on neurovascular injury.

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