Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Rodrigues‐Neves, Ana Catarina; Carecho, Rafael; Correia, Sónia C.; Carvalho, Cristina; Campos, Elisa J.; Baptista, Filipa I.; Moreira, Paula I.; Ambrósio, António Francisco

doi:10.1007/s12035-021-02316-x

Cited by 10 publications

(12 citation statements)

References 65 publications

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“…In contrast, another report showed tangles of hyperphosphorylated tau in the RGCL of young mice by using the same antibody (1.5–2.5 months of age) [ 96 ]. More recently, Rodrigues-Neves and colleagues [ 98 ] corroborated previous results by reporting an increase in phosphorylated tau at Ser396 in the retina of 3xTg-AD mice at both 4 and 8 months of age. Strikingly, a study revealed that an N-terminal-domain truncated tau is associated with the degeneration of the retinas of Tg2576 transgenic mice (carrying a mutant form of APP linked to early-onset familial AD), highlighting the role of other post-transcriptional modifications of tau during AD progress [ 104 ].…”

Section: Ocular Alterations Related To Adsupporting

confidence: 55%

“…Although the presence of Aβ plaques in the retina was reported in pre-symptomatic 3xTg-AD mice (including RGC death by apoptosis), this Aβ host was not detected in inner retinal layers until approximately 7 weeks of age (middle-aged mice) [ 96 ]. However, recent advances have refuted or nuanced these achievements [ 97 , 98 ]. Significantly RGC dendritic loss was detected in 3xTg-AD mice at 12 months of age (old mice) but not at 6–7 months, and it was not accompanied by a reduction in the number of RGCL nuclei [ 97 ].…”

Section: Ocular Alterations Related To Admentioning

confidence: 99%

“…Significantly RGC dendritic loss was detected in 3xTg-AD mice at 12 months of age (old mice) but not at 6–7 months, and it was not accompanied by a reduction in the number of RGCL nuclei [ 97 ]. Strikingly, Rodrigues-Neves and colleagues did not find retinal changes regarding Aβ levels, retinal cell death by apoptosis, or decreased RGCs when looking at early stages in 3xTg-AD mice (4–8 months of age) [ 98 ].…”

Section: Ocular Alterations Related To Admentioning

confidence: 99%

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Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

Romaus-Sanjurjo

Regueiro

López-López

et al. 2022

IJMS

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Alzheimer’s Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aβ) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.

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Section: Ocular Alterations Related To Adsupporting

confidence: 55%

Section: Ocular Alterations Related To Admentioning

confidence: 99%

Section: Ocular Alterations Related To Admentioning

confidence: 99%

See 1 more Smart Citation

Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

Romaus-Sanjurjo

Regueiro

López-López

et al. 2022

IJMS

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“…The previous data demonstrated that neurotransmitter level (GABA and glutamate) and Aβ, and also hyperphosphorylated Tau protein, are not significantly altered in the brain cortex, hippocampus, and retina at an early stage in the experimental model of AD (3×Tg mouse model) [133]. However, this study simultaneously demonstrated a few differential changes of microglia in retina and brain regions, which means different profiles in microglia branching at this early stage of AD (4-month-old AD-Tg mouse) with hypertrophy of microglia in the hippocampus and atrophic morphology of microglia in the retina.…”

Section: Glutamatergic Signaling In Microglia-neuron Communication In Admentioning

confidence: 98%

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Czapski

Strosznajder

2021

IJMS

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The physiological balance between excitation and inhibition in the brain is significantly affected in Alzheimer’s disease (AD). Several neuroactive compounds and their signaling pathways through various types of receptors are crucial in brain homeostasis, among them glutamate and γ-aminobutyric acid (GABA). Activation of microglial receptors regulates the immunological response of these cells, which in AD could be neuroprotective or neurotoxic. The novel research approaches revealed the complexity of microglial function, including the interplay with other cells during neuroinflammation and in the AD brain. The purpose of this review is to describe the role of several proteins and multiple receptors on microglia and neurons, and their involvement in a communication network between cells that could lead to different metabolic loops and cell death/survival. Our review is focused on the role of glutamatergic, GABAergic signaling in microglia–neuronal cross-talk in AD and neuroinflammation. Moreover, the significance of AD-related neurotoxic proteins in glutamate/GABA-mediated dialogue between microglia and neurons was analyzed in search of novel targets in neuroprotection, and advanced pharmacological approaches.

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“…The restoration of blood supply followed by a period of ischemia that leads to injury, termed ischemia-reperfusion injury (IRI), is viewed as a characteristic of ischemic stroke [ 2 ]. Retina, as a developmental extension of the brain sharing various common pathophysiological alterations with the brain [ 3 , 4 ], is highly likely to be affected while cerebral stroke occurs. The loss of visual function due to apoptosis, necrosis, and pyroptosis has been extensively studied in several inflammatory disorders [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3/Caspase-1/GSDMD Pathway in Retina or Brain Neuron following Rat Ischemia/Reperfusion

Yang

Liu

et al. 2022

Brain Sciences

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Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H2S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 μmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H2S could constitute a novel therapeutic strategy for ischemic stroke.

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Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Cited by 10 publications

References 65 publications

Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3/Caspase-1/GSDMD Pathway in Retina or Brain Neuron following Rat Ischemia/Reperfusion

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