The amyloidogenic potential and behavioral correlates of stress

Catania, Caterina; Sotiropoulos, Ioannis; Silva, R.; Onofri, Chiara; Breen, Kieran C.; Sousa, Nuno; Almeida, Osborne F. X.

doi:10.1038/sj.mp.4002101

Cited by 161 publications

(139 citation statements)

References 68 publications

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“…It is likely that social isolation led to oxidative stress (Schiavone et al, 2009), which in turn stimulated b-and g-secretase activity (Chan et al, 2009) resulting in increased Ab, which then triggered onset of cognition decline in the APP/PS1 mice. These results are consistent with previous reports showing that stress and glucocorticoids similarly promote APP processing along the amyloidogenic pathway (Catania et al, 2009) resulting in the exacerbation of AD-like neuropathology (Billings et al, 2005;Green et al, 2006;Jeong et al, 2006;Srivareerat et al, 2009).…”

Section: Acceleration Of Memory Impairment By Social Isolationsupporting

confidence: 83%

The Involvement of Cdk5 Activator p35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice

Hsiao

Chen

et al. 2011

Neuropsychopharmacol

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Epidemiological studies indicate that isolated persons have increased risk of developing Alzheimer's disease (AD). This study investigated the cellular mechanisms of how social isolation influenced amyloid b peptide (Ab) accumulation and affected the severity of AD-associated cognitive decline in a mouse model of AD. Amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice were placed either in isolation or in group from postnatal day 28 and tested for cognitive performance at the age of 3 months with fear-conditioning paradigms. We found that social isolation accelerated impairment of contextual fear memory in the APP/PS1 mice. The magnitude of long-term potentiation in the hippocampal CA1 neurons was significantly lower in the isolated APP/PS1 mice compared with group APP/PS1 and wild-type mice. Hippocampal level of Ab was significantly elevated in the isolated APP/PS1 mice, which was accompanied by an increased calpain activity and p25/p35 ratio. In addition, surface expression of GluR1 subunit of AMPA receptor was decreased by social isolation. The association of p35, and a-CaMKII was significantly less in the isolated APP/PS1 mice indicating that their interaction was impaired. These results suggest that social isolation exacerbates memory deficit by increasing Ab level, leading to the increased calpain activity, conversion of p35 to p25 and decrease in association of p35, a-CaMKII, and GluR1, resulting in the endocytosis of AMPA receptors.

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Section: Acceleration Of Memory Impairment By Social Isolationsupporting

confidence: 83%

The Involvement of Cdk5 Activator p35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice

Hsiao

Chen

et al. 2011

Neuropsychopharmacol

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“…This is in line with the observations that major stressful events lower the age of onset of familial AD (Mejia et al, 2003). In various preclinical AD models, stress worsens deficits in hippocampus-dependent spatial learning (Catania et al, 2009;Cuadrado-Tejedor et al, 2012;Dong et al, 2004;Jeong et al, 2006;Srivareerat et al, 2009;Tran et al, 2010). These deleterious effects are in part caused by an accelerated accumulation of Ab under stressing conditions (Catania et al, 2009;Cuadrado-Tejedor et al, 2012;Dong et al, 2004;Green et al, 2006;Jeong et al, 2006;Srivareerat et al, 2009).…”

Section: Introductionsupporting

confidence: 73%

“…In various preclinical AD models, stress worsens deficits in hippocampus-dependent spatial learning (Catania et al, 2009;Cuadrado-Tejedor et al, 2012;Dong et al, 2004;Jeong et al, 2006;Srivareerat et al, 2009;Tran et al, 2010). These deleterious effects are in part caused by an accelerated accumulation of Ab under stressing conditions (Catania et al, 2009;Cuadrado-Tejedor et al, 2012;Dong et al, 2004;Green et al, 2006;Jeong et al, 2006;Srivareerat et al, 2009). Stress triggers the release of glucocorticoid hormones (CORT), the major output of the hypothalamopituitary-adrenal axis (HPA).…”

Section: Introductionmentioning

confidence: 99%

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Lanté

Chafaï

Raymond

et al. 2015

Neuropsychopharmacol

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The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset.

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“…Although no data are available on the effects of A␤ peptide injection on hypothalamic-pituitary-adrenal axis activity, several studies have demonstrated that glucocorticoids modulate APP processing, 55 increase A␤ 1-42 -induced neurodegeneration in basal nuclei of Meynert, 56 and increase A␤ [25][26][27][28][29][30][31][32][33][34][35] toxicity in hippocampus neurons. 57 Moreover, in vivo chronic corticosterone administration was shown to increase A␤ and N-methyl-D-aspartate-induced neurodegeneration in cholinergic neurons from the nucleus basalis in the rat.…”

Section: Discussionmentioning

confidence: 99%

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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The amyloidogenic potential and behavioral correlates of stress

Cited by 161 publications

References 68 publications

The Involvement of Cdk5 Activator p35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice

The Involvement of Cdk5 Activator p35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

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

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