Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I decreases survival of dentate granule neurons: Insights into the regulation of adult hippocampal neurogenesis

Lichtenwalner, Robin J.; Forbes, M. Elizabeth; Sonntag, William E.; Riddle, David R.

doi:10.1002/jnr.20719

Cited by 60 publications

(58 citation statements)

References 79 publications

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“…Thus, it is of particular interest that deletion of MOR appears to confer a survival advantage to maturing neurons without altering the numbers of proliferating progenitor cells. These data add MOR to the limited list of factors that have a stronger effect on survival versus proliferation of new hippocampal neurons (Ambrogini et al, 2005, Rizk et al, 2005, Galea et al, 2006, Lichtenwalner et al, 2006. The data presented here suggest that MOR is critical to normal maturation of adult-generated granule cells.…”

Section: Discussionsupporting

confidence: 52%

Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons

Harburg¹,

Hall²,

Harrist³

et al. 2007

Neuroscience

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Recent evidence suggests that mu opioid receptors (MOR) are key regulators of hippocampal structure and function. For example, exogenous MOR agonists morphine and heroin negatively impact hippocampal function and decrease adult hippocampal neurogenesis. Here we explored the role of MOR in the birth and survival of hippocampal progenitor cells by examining adult neurogenesis in mice that lack MOR. Adult male mice lacking exon 1 of MOR were injected with the S phase marker bromodeoxyuridine (BrdU) and sacrificed either two hours or four weeks later to evaluate proliferating and surviving BrdU-immunoreactive (IR) cells, respectively, in the adult hippocampal granule cell layer. WT, heterozygote, and homozygote mice did not differ in the number of BrdU-IR cells at a proliferation time point. However, four weeks after BrdU injection, heterozygote and homozygote mice had 57% and 54% more surviving BrdU-IR cells in the hippocampal granule cell layer as compared to WT mice. A decrease in apoptosis in the heterozygote and homozygote mice did not account for the difference in number of surviving BrdU-IR cells since there were no alterations in number of pyknotic, TUNEL-positive, or activated caspase 3-IR cells compared to WT. In concordance with the increased numbers of granule cells maturing into neurons, heterozygote and homozygote mice had larger hippocampal granule cell layers and increased numbers of granule cells. These findings indicate that MOR may play a role in regulating progenitor cell survival and more generally encourage further exploration of how MOR activation can influence hippocampal structure and function.

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Section: Discussionsupporting

confidence: 52%

Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons

Harburg¹,

Hall²,

Harrist³

et al. 2007

Neuroscience

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“…BrdU labeling has been used extensively in the study of replication and cell cycle phenomena in eukaryotes (13,16,17,18) and to a lesser extent in the investigation of bacterial activity (4,20,21). BrdU is a thymidine analog that is incorporated into the DNA of replicating cells.…”

Section: Resultsmentioning

confidence: 99%

Spatial Patterns of DNA Replication, Protein Synthesis, and Oxygen Concentration within Bacterial Biofilms Reveal Diverse Physiological States

Rani¹,

Pitts²,

Beyenal³

et al. 2007

J Bacteriol

290

233

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It has long been suspected that microbial biofilms harbor cells in a variety of activity states, but there have been few direct experimental visualizations of this physiological heterogeneity. Spatial patterns of DNA replication and protein synthetic activity were imaged and quantified in staphylococcal biofilms using immunofluorescent detection of pulse-labeled DNA and also an inducible green fluorescent protein (GFP) construct. Stratified patterns of DNA synthetic and protein synthetic activity were observed in all three biofilm systems to which the techniques were applied. In a colony biofilm system, the dimensions of the zone of anabolism at the air interface ranged from 16 to 38 m and corresponded with the depth of oxygen penetration measured with a microelectrode. A second zone of activity was observed along the nutrient interface of the biofilm. Much of the biofilm was anabolically inactive. Since dead cells constituted only 10% of the biofilm population, most of the inactive cells in the biofilm were still viable. Collectively, these results suggest that staphylococcal biofilms contain cells in at least four distinct states: growing aerobically, growing fermentatively, dead, and dormant. The variety of activity states represented in a biofilm may contribute to the special ecology and tolerance to antimicrobial agents of biofilms.

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“…Additionally, following CNS injury, IGF-1 has also been found to increase progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus (Aberg et al, 2006). In contrast, deficiency in GH and IGF-I decreases survival of dentate granule neurons (Lichtenwalner et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Effect of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

High

Briones-Galang

Clark

et al. 2010

Journal of Neurotrauma

143

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Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

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Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I decreases survival of dentate granule neurons: Insights into the regulation of adult hippocampal neurogenesis

Cited by 60 publications

References 79 publications

Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons

Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons

Spatial Patterns of DNA Replication, Protein Synthesis, and Oxygen Concentration within Bacterial Biofilms Reveal Diverse Physiological States

Effect of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

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