Stereological estimation of neuron number and plaque load in the hippocampal region of a transgenic rat model of <scp>A</scp>lzheimer's disease

Heggland, Ingrid; Storkaas, Inge S.; Soligard, H; Kobro‐Flatmoen, Asgeir; Witter, Menno P.

doi:10.1111/ejn.12876

Cited by 49 publications

(68 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease in the numbers of neurons in CA1 and DG is in agreement with previous studies reporting neuronal loss in CA1 [74–78] and DG [1, 77, 78] in AD. However, our data are inconsistent with one recent study [79], which reported that a significant reduction in neurons was only observed in the subiculum of the McGill-R-Thy1-APP transgenic rat model of AD at 18 months of age [79]. This discrepancy may be related to the differences in the transgenes and strains of the animals studied.…”

Section: Discussioncontrasting

confidence: 99%

“…This discrepancy may be related to the differences in the transgenes and strains of the animals studied. The McGill-R-Thy1-APP transgenic rats possess only a single transgene, and in these animals, the first Aβ plaque pathology is evident at about 9 months of age in the subiculum [79], while our APPswe/PSEN1dE9 mice show Aβ plaque pathology as early as at 4-6 months of age in the hippocampus [52–55]. Strikingly, Gan et al [80] have reported that the number of neural progenitor cells is significantly decreased at the stages of Aβ plaque onset and progression.…”

Section: Discussionmentioning

confidence: 99%

“…Strikingly, Gan et al [80] have reported that the number of neural progenitor cells is significantly decreased at the stages of Aβ plaque onset and progression. Heggland et al have considered that it is possible that at older ages, cell loss would become apparent in other brain areas in the McGill-R-Thy1-APP transgenic rat, since the progression of pathology is gradual [79]. They also predicted that although rats, given their larger size as well as more social and complex behaviors, are considered to be physiologically and genetically closer to humans than mice [81], neuronal loss has only been reported in one rat transgenic model, the TgF344-AD line [82], and transgenic mouse models have been more widely used in studies.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

Gao

Jiang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer’s disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

Gao

Jiang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Neuronal loss is a typical feature in AD as reported [46, 47]. Our data showed a sharply reduced of cell numbers in aged mice brains, especially in hippocampal CA1 and CA3 subregions.…”

Section: Discussionsupporting

confidence: 81%

Tissue Transglutaminase and Its Product Isopeptide Are Increased in Alzheimer’s Disease and APPswe/PS1dE9 Double Transgenic Mice Brains

et al. 2015

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by intracellular and extracellular protein aggregates, including microtubule-associated protein tau and cleavage product of amyloid precursor protein, β-amyloid (Aβ). Tissue transglutaminase (tTG) is a calcium-dependent enzyme that cross-links proteins forming a γ-glutamyl-ε-lysine isopeptide bond. Highly resistant to proteolysis, this bond can induce protein aggregation and deposition. We set out to determine if tTG may play a role in pathogenesis of AD. Previous studies have shown that tTG and isopeptide are increased in advanced AD, but they have not addressed if this is an early or late feature of AD. In the present study, we measured tTG expression levels and enzyme activity in the brains of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD, as well as a transgenic mouse model of AD. We found that both enzyme expression and activity were increased in MCI as well as AD compared to NCI. In the transgenic model of AD, tTG expression and enzyme activity increased sharply with age and were relatively specific for the hippocampus. We also assessed overlap of isopeptide immunoreactivity with neurodegeneration-related proteins with Western blots and found neurofilament, tau, and Aβ showed co-localization with isopeptide in both AD and transgenic mice. These results suggest that tTG might be a key factor in pathogenesis of abnormal protein aggregation in AD.

show abstract

“…The loss of neurons is a typical feature of AD [14,41] . It has been reported that neuronal apoptosis occurs in AD pathogenesis [42,43] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of tissue transglutaminase promotes Aβ-induced apoptosis in SH-SY5Y cells

2016

View full text Add to dashboard Cite

Aim: Tissue transglutaminase (tTG) catalyzes proteins, including β-amyloid (Aβ), to cross-link as a γ-glutamyl-ε-lysine structure isopeptide, which is highly resistant to proteolysis. Thus, tTG plays an important role in protein accumulation in Alzheimer's disease (AD). In the present study, we examined the effect of an irreversible tTG inhibitor, NTU283, on Aβ mimic-induced AD pathogenesis in SH-SY5Y cells. Methods: Western blot and in-cell Western analyses were used to detect tTG and isopeptide (representing the enzyme activity of tTG) protein levels. Moreover, Hoechst and PI co-staining was performed, and caspase-3 and caspase-7 activities and the Bax/Bcl-2 ratio were determined to evaluate the effects of NTU283 on apoptosis. Results:The results confirmed that tTG activity was inhibited by NTU283 20-500 μmol/L in a concentration-dependent manner in SH-SY5Y cells. Contrary to our expectations, however, the isopeptide bonds were increased when cells were co-treated with Aβ and NTU283. In addition, NTU283 alone did not induce apoptosis in SH-SY5Y cells. However, when co-applied with Aβ, NTU283 promoted rather than inhibited Aβ-induced apoptosis. Consistent with the apoptotic rate, pretreating cells with different concentrations of NTU283 and Aβ significantly increased the activities of caspase-3 and caspase-7 as well as the ratio of Bax/Bcl-2. Conclusion: Irreversible inhibition of tTG activity did not block but rather promoted Aβ-induced apoptosis, which indicated that tTG has complex functions in AD pathogenesis.

show abstract

Stereological estimation of neuron number and plaque load in the hippocampal region of a transgenic rat model of Alzheimer's disease

Cited by 49 publications

References 72 publications

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

Tissue Transglutaminase and Its Product Isopeptide Are Increased in Alzheimer’s Disease and APPswe/PS1dE9 Double Transgenic Mice Brains

Inhibition of tissue transglutaminase promotes Aβ-induced apoptosis in SH-SY5Y cells

Contact Info

Product

Resources

About