Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model

Orejana, Lourdes; Barros-Miñones, Lucía; Jordán, Joaquı́n; Puerta, Elena; Aguirre, Norberto

doi:10.1016/j.neurobiolaging.2011.03.018

Cited by 57 publications

(48 citation statements)

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“…One of these substrains, the senescenceaccelerated mouse prone-8 (SAMP8) strain manifests irreversible advancing senescence and shares similar characteristics with aged humans such as a reduced lifespan, lordosis, hair loss, and reduced physical activity (Hamamoto et al, 1984;Takeda et al, 1994), whereas the senescence-accelerated mice resistant-1 (SAMR1) strain presents a normal ageing pattern (Takeda, 1999). Interestingly, SAMP8 mice also exhibit age-related learning and memory deficits, as well as amyloid-like deposits in the brain (Del Valle et al, 2010;Tomobe and Nomura, 2009) and increased expression of hyperphosphorylated Tau (Canudas et al, 2005;Orejana et al, 2012). Given such features, SAMP8 mice have been proposed as suitable rodent model for studying age-associated pathologies (Tomobe and Nomura, 2009), or even as an AD animal model (Liu et al, 2010;Pallas et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

et al. 2013

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Section: Introductionmentioning

confidence: 99%

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

et al. 2013

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“…Apart from the efficacy of PDE5 inhibitors in the treatment of erectile dysfunction or pulmonary arterial hypertension (Mostafa, 2008), experimental data show that sildenafil enhances angiogenesis and neurogenesis and improves functional outcome during stroke recovery (Ding et al, 2008), improves learning and memory in the Tg2576 model of Alzheimer's disease and in a senescence accelerated mouse model (Cuadrado-Tejedor et al, 2011;Orejana et al, 2011), and prevents the neurotoxic effects of 3-nitropropionic acid (Puerta et al, 2010a). Moreover, we have recently shown that sildenafil given shortly before MDMA affords complete protection against MDMA-induced 5-HT depletions by opening mitochondrial ATP-sensitive K 1 channels, a key mechanism involved acute preconditioning paradigms (Puerta et al, 2009b).…”

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confidence: 99%

Long‐lasting neuroprotective effect of sildenafil against 3,4‐methylenedioxymethamphetamine‐ induced 5‐hydroxytryptamine deficits in the rat brain

Puerta

Barros-Miñones

Hervías

et al. 2011

J of Neuroscience Research

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Sildenafil, given shortly before 3,4-methylenedioxymethamphetamine (MDMA), affords protection against 5-hydroxytryptamine (5-HT) depletions caused by this amphetamine derivative by an acute preconditioning-like mechanism. Because acute and delayed preconditionings do not share the same mechanisms, we investigated whether sildenafil would also protect the 5-HT system of the rat if given 24 hr before MDMA. For this, MDMA (3 × 5 mg/kg i.p., every 2 hr) was administered to rats previously treated with sildenafil (8 mg/kg p.o.). One week later, 5-HT content and 5-HT transporter density were measured in the striatum, frontal cortex, and hippocampus of the rats. Our findings indicate that sildenafil afforded significant protection against MDMA-induced 5-HT deficits without altering the acute hyperthermic response to MDMA or its metabolic disposition. Sildenafil promoted ERK1/2 activation an effect that was paralleled by an increase in MnSOD expression that persisted 24 hr later. In addition, superoxide and superoxide-derived oxidants, shown by ethidium fluorescence, increased after the last MDMA injection, an effect that was prevented by sildenafil pretreatment. Similarly, MDMA increased nitrotyrosine concentration in the hippocampus, an effect not shown by sildenafil-pretreated rats. In conclusion, our data demonstrate that sildenafil produces a significant, long-lasting neuroprotective effect against MDMA-induced 5-HT deficits. This effect is apparently mediated by an increased expression of MnSOD and a subsequent reduced susceptibility to the oxidative stress caused by MDMA.

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“…SAMP8 mice have been reported to accumulate Aβ in the brain, where it forms senile plaques. 24) SAMP8 mice have deficits of learning and memory at age 6 months 25,26) and 12 months 27,28) compared with SAMR1 mice in the Morris water maze. The oxidative stress level in these mice is also increased from 6 to 12 months.…”

Section: )mentioning

confidence: 98%

“…Thus, we quantified the accumulation of Aβ40. A standard peptide and the samples were incubated in microplates coated with the monoclonal antibody BNT77, which recognizes human and rat Aβ (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), for 1 h at 4°C. After washing five times, the plates were incubated with an HRP-conjugated antibody raised against the C-terminus of Aβ40 for 1 h at 4°C.…”

Section: )mentioning

confidence: 99%

“…Alternation rate (%) was calculated as the number of actual alternations performed divided by the number of possible alternations (defined as the number of arm entries minus two) multiplied by 100. [19][20][21][22][23][24][25][26][27][28][29][30] Immunostaining of SAMP8, SAMR1, and Tg2576 mouse brain slices. The remaining brain hemispheres were fixed in 10% formaldehyde and then embedded in paraffin.…”

Section: Spontaneous Alternation In a Y-maze Testmentioning

confidence: 99%

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Aβ induces oxidative stress in senescence-accelerated (SAMP8) mice

Takagane

Nojima

Mitsuhashi

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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According to the amyloid hypothesis, amyloid β accumulates in brains with Alzheimer’s disease (AD) and triggers cell death and memory deficit. Previously, we developed a rice Aβ vaccine expressing Aβ, which reduced brain Aβ levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated SAMP8 mice as a model of sporadic AD and investigated the relationship between Aβ and oxidative stress. Insoluble Aβ and 4-hydroxynonenal (4-HNE) levels tended to be reduced in SAMP8 mice-fed the rice Aβ vaccine. We attempted to clarify the relationship between oxidative stress and Aβ in vitro. Addition of Aβ peptide to the culture medium resulted in an increase in 4-HNE levels in SH-SY5Y cells. Tg2576 mice, which express large amounts of Aβ in their brain, also exhibited increased 4-HNE levels; this increase was inhibited by the Aβ vaccine. These results indicate that Aβ induces oxidative stress in cultured cells and in the mouse brain.

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Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model

Cited by 57 publications

References 65 publications

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

Long‐lasting neuroprotective effect of sildenafil against 3,4‐methylenedioxymethamphetamine‐ induced 5‐hydroxytryptamine deficits in the rat brain

Aβ induces oxidative stress in senescence-accelerated (SAMP8) mice

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