Amyloid-β(25–35)-induced memory impairments correlate with cell loss in rat hippocampus

Stepanichev, M. Yu.; Zdobnova, Irina M.; Zarubenko, I. I.; Moiseeva, Yulia; Лазарева, Н. А.; Онуфриев, М. В.; Gulyaeva, N. V.

doi:10.1016/j.physbeh.2003.11.003

Cited by 129 publications

(64 citation statements)

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“…At 1 week after injection, A␤ [25][26][27][28][29][30][31][32][33][34][35] induced significant oxidative stress in the hippocampus, as reflected by measured increases in lipid peroxidation, protein nitration, and superoxide generation. [11][12][13]40 In the present study, the early increases in lipid peroxidation levels observed after peptide injection were gradually reduced, particularly in the rat frontal cortex and amygdala, suggesting that oxidative stress could be alleviated by endogenous protective systems (putatively neurotrophins, such as BDNF).…”

Section: Discussionsupporting

confidence: 51%

“…C: Effects of A␤ [25][26][27][28][29][30][31][32][33][34][35] (10 g/rat) intracerebroventricular injection on hippocampus DG neurogenesis using PSA-NCAM immunolabeling, determined in untreated control rats and at 1, 2, and 3 weeks after A␤ [25][26][27][28][29][30][31][32][33][34][35] reactive gliosis, by up-regulation of GFAP expression, and hypertrophic astrocytes were observed in the hippocampus (present study and Ref. 13); in the present study, hypertrophic astrocytes were observed also in the frontal and parietal cortex, amygdala, and hypothalamus. Moreover, we observed that A␤ [25][26][27][28][29][30][31][32][33][34][35] injection also increased Iba-1 immunoreactivity, a marker of activated microglia, and the increase was associated with progressive hypertrophy and hyper-ramification of these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Numbers of neurons in the different hippocampal fields were counted as described previously. 9,10,13 Counting was performed using a light microscope (Leica DMR). Digitized images were acquired using a 40ϫ objective and were analyzed with ImageJ software.…”

Section: Histologymentioning

confidence: 99%

“…In particular, at 1 week after A␤ [25][26][27][28][29][30][31][32][33][34][35] injection, reactive gliosis was observed in the rat hippocampus, 9 caspase-3 activity was induced in the hippocampus and cortex, 9 a reduction in the number of neurons was measured in the CA1 or CA3 hippocampal area, 9 -11 and significant oxidative stress was observed. [11][12][13] Nonetheless, this amyloid toxicity model remains controversial with respect to AD. The grounds for objection center on three points.…”

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confidence: 99%

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Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Zussy

Brureau

Delair

et al. 2011

The American Journal of Pathology

121

129

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Alzheimer's disease (AD) is a neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss. The major component of senile plaques is an amyloid ␤ protein (A␤) formed by pathological processing of the A␤ precursor protein. We assessed the time-course and regional effects of a single intracerebroventricular injection of aggregated A␤ fragment 25-35 (A␤ 25-35 ) in rats. Using a combined biochemical, behavioral, and morphological approach, we analyzed the peptide effects after 1, 2, and 3 weeks in the hippocampus, cortex, amygdala, and hypothalamus. The scrambled A␤ 25-35 peptide was used as negative control. The aggregated forms of A␤ peptides were first characterized using electron microscopy, infrared spectroscopy, and Congo Red staining. Intracerebroventricular injection of A␤ 25-35 decreased body weight, induced short-and long-term memory impairments, increased endocrine stress, cerebral oxidative and cellular stress, neuroinflammation, and neuroprotective reactions, and modified endogenous amyloid processing, with specific time-course and regional responses. Moreover, A␤ 25-35 , the presence of which was shown in the different brain structures and over 3 weeks, provoked a rapid glial activation, acetylcholine homeostasis perturbation, and hippocampal morphological alterations. Alzheimer's disease (AD) is a chronic neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss in brain areas responsible for learning and memory impairments. 1 The major component of senile plaques is an amyloid ␤ protein (A␤) derived from amyloid precursor protein (APP). Genetic, cell biological, and postmortem studies on AD brain, together with A␤ neurotoxicity findings, gave rise to the amyloid cascade hypothesis to explain A␤-associated neurodegenerative processes. 2 In normal healthy individuals, A␤ peptides are present only in small quantities, as soluble monomers that circulate in cerebrospinal fluid and blood. In AD patients, A␤ peptides, which vary in length from 40 to 43 amino acids, accumulate as insoluble fibrillar deposits. 3 When cultured rat hippocampal neurons are exposed to aggregated A␤ peptides, their neurites adopt a dystrophic appearance and become comparable to those observed surrounding and infiltrating senile plaques. This observation suggested that A␤ is responsible for the neuritic abnormalities in AD pathology. 4 Structure-activity studies revealed that peptides containing the highly hydrophobic 25-35 region formed stable aggregates and mediated neuronal death by necrosis or apoptosis. 5,6,7 The truncated A␤ 25-35 fragment includes extracellular and intramembrane residues that have been reported to represent an active region of A␤. 8

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Histologymentioning

confidence: 99%

mentioning

confidence: 99%

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Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Zussy

Brureau

Delair

et al. 2011

The American Journal of Pathology

121

129

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“…A rodent pharmacological study showed that WM impairment was accompanied by the deposition of Amyloid beta-peptide (Abeta) in the hippocampus (Leighty et al, 2004). Moreover, WM damage induced by Abeta administration was correlated with neuronal cell loss in the hippocampus (Stepanichev et al, 2004). Lesion studies on humans also showed that patients with medial temporal lobe damages had WM impairment (Ezzyat and Olson, 2008;Olson et al, 2006a,b).…”

Section: Introductionmentioning

confidence: 99%

The NTSR1 gene modulates the association between hippocampal structure and working memory performance

Jin¹,

Lei²,

Wang³

et al. 2013

NeuroImage

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The genetic and neural basis of working memory (WM) has been extensively studied. Many dopamine (DA) related genes, including the NTSR1 gene (a DA modulator gene), have been reported to be associated with WM performance. The NTSR1 protein is predominantly expressed in the cerebral cortex and the hippocampus, the latter of which is closely involved in WM processing based on both lesion and fMRI studies. Thus far, however, no study has examined the joint effects of NTSR1 gene polymorphism and hippocampal morphology on WM performance. Participants of the current study were 330 healthy Chinese college students. WM performance was measured with a 2-back WM paradigm. Structural MRI data were acquired and then analyzed using an automated procedure with atlas-based FreeSurfer segmentation software (v 4.5.0) package. Linear regression analyses were conducted with a NTSR1 C/T polymorphism which was previously reported to be associated with WM (rs4334545), hippocampal volume, and their interaction as predictors of WM performance, with gender and intracranial volume (ICV) as covariates. Results showed a significant interaction between NTSR1 genotype and hippocampal volume (p b .05 for both the left and right hippocampi). Further analysis showed that the correlation between hippocampal volume and WM scores was significant for carriers of the NTSR1 T-allele (p b .05 for both hippocampi), but not for CC homozygotes. These results indicate that the association between hippocampal structure and WM performance was modulated by variation in the NTSR1 gene, and suggest that further studies of brain-behavior associations should take genetic background information into account.

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Beta‐amyloid protein (25–35) disrupts hippocampal network activity: Role of Fyn‐kinase

et al. 2009

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Early cognitive deficit characteristic of early Alzheimer's disease seems to be produced by the soluble forms of beta-amyloid protein. Such cognitive deficit correlates with neuronal network dysfunction that is reflected as alterations in the electroencephalogram of both Alzheimer patients and transgenic murine models of such disease. Correspondingly, recent studies have demonstrated that chronic exposure to betaAP affects hippocampal oscillatory properties. However, it is still unclear if such neuronal network dysfunction results from a direct action of betaAP on the hippocampal circuit or it is secondary to the chronic presence of the protein in the brain. Therefore, we aimed to explore the effect of acute exposure to betaAP(25-35) on hippocampal network activity both in vitro and in vivo, as well as on intrinsic and synaptic properties of hippocampal neurons. We found that betaAP(25-35), reversibly, affects spontaneous hippocampal population activity in vitro. Such effect is not produced by the inverse sequence betaAP(35-25) and is reproduced by the full-length peptide betaAP(1-42). Correspondingly betaAP(25-35), but not the inverse sequence betaAP(35-25), reduces theta-like activity recorded from the hippocampus in vivo. The betaAP(25-35)-induced disruption in hippocampal network activity correlates with a reduction in spontaneous neuronal activity and synaptic transmission, as well as with an inhibition in the subthreshold oscillations produced by pyramidal neurons in vitro. Finally, we studied the involvement of Fyn-kinase on the betaAP(25-35)-induced disruption in hippocampal network activity in vitro. Interestingly, we found that such phenomenon is not observed in slices obtained from Fyn-knockout mice. In conclusion, our data suggest that betaAP acutely affects proper hippocampal function through a Fyn-dependent mechanism. We propose that such alteration might be related to the cognitive impairment observed, at least, during the early phases of Alzheimer's disease.

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Amyloid-β(25–35)-induced memory impairments correlate with cell loss in rat hippocampus

Cited by 129 publications

References 38 publications

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

The NTSR1 gene modulates the association between hippocampal structure and working memory performance

Beta‐amyloid protein (25–35) disrupts hippocampal network activity: Role of Fyn‐kinase

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