The Chick as a Model for the Study of the Cellular Mechanisms and Potential Therapies for Alzheimer's Disease

Mileusnic, Radmila; Rose, Steven

doi:10.4061/2010/180734

Cited by 5 publications

(7 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vertebrate non-mammalian species are also highly valuable translational models. For instance, besides being a classical model for epilepsy (see for instance Douaud et al, 2011 for recent studies) the domestic chick is a well-established model for the study of the cellular mechanisms of memory and potential therapies for dementia diseases (Mileusnic and Rose, 2010 ). Furthermore, studies on precocial social species have permitted the formulation of original hypothesis on some developmental disturbances such as autism.…”

Section: Discussionmentioning

confidence: 99%

Origins of Knowledge: Insights from Precocial Species

Versace

Vallortígara

2015

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Behavioral responses are influenced by knowledge acquired during the lifetime of an individual and by predispositions transmitted across generations. Establishing the origin of knowledge and the role of the unlearned component is a challenging task, given that both learned and unlearned knowledge can orient perception, learning, and the encoding of environmental features since the first stages of life. Ethical and practical issues constrain the investigation of unlearned knowledge in altricial species, including human beings. On the contrary, precocial animals can be tested on a wide range of tasks and capabilities immediately after birth and in controlled rearing conditions. Insects and precocial avian species are very convenient models to dissect the knowledge systems that enable young individuals to cope with their environment in the absence of specific previous experience. We present the state of the art of research on the origins of knowledge that comes from different models and disciplines. Insects have been mainly used to investigate unlearned sensory preferences and prepared learning mechanisms. The relative simplicity of the neural system and fast life cycle of insects make them ideal models to investigate the neural circuitry and evolutionary dynamics of unlearned traits. Among avian species, chicks of the domestic fowl have been the focus of many studies, and showed to possess unlearned knowledge in the sensory, physical, spatial, numerical and social domains. Solid evidence shows the existence of unlearned knowledge in different domains in several species, from sensory and social preferences to the left-right representation of the mental number line. We show how non-mammalian models of cognition, and in particular precocial species, can shed light into the adaptive value and evolutionary history of unlearned knowledge.

show abstract

Section: Discussionmentioning

confidence: 99%

Origins of Knowledge: Insights from Precocial Species

Versace

Vallortígara

2015

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…We therefore asked whether the embryonic chick retina, which expresses PHF-1 tau, might also briefly express AβOs. This possibility is in harmony with the fact that chicks express the same amino acid sequence of Aβ42 as humans [38,69], which favors oligomer formation [20,70,71]. We first tested for the presence of AβOs using a sensitive dot immunoblot assay.…”

Section: Alzheimer's-linked Aβos and Ptau Are Expressed In The Embryo...mentioning

confidence: 97%

“…The formation of AβOs depends on Aβ released by BACE, also known as beta secretase, from amyloid precursor protein (APP), both of which are known to be present in the chick retina [38,69]. BACE and APP development was tracked here using A4 and D10E5 antibodies, respectively (Figures S3 and S4).…”

Section: Aβo Proteoforms Differ In Spatiotemporal Expressionmentioning

confidence: 99%

“…Experiments were performed with the developing chick. Chicks are one of a number of species that retain the human Aβ42 sequence [37][38][39][40]), and developing chicks are known to transiently express a phospho-tau proteoform (pSer396/404) stimulated in various experimental models by AβOs [29,[41][42][43]. Experiments have focused on the retina, which is widely used as a model in studies of neural development [44][45][46][47][48][49][50][51][52][53][54][55][56].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis

Bartley

Proctor

Xia

et al. 2022

IJMS

View full text Add to dashboard Cite

Human amyloid beta peptide (Aβ) is a brain catabolite that at nanomolar concentrations can form neurotoxic oligomers (AβOs), which are known to accumulate in Alzheimer’s disease. Because a predisposition to form neurotoxins seems surprising, we have investigated whether circumstances might exist where AβO accumulation may in fact be beneficial. Our investigation focused on the embryonic chick retina, which expresses the same Aβ as humans. Using conformation-selective antibodies, immunoblots, mass spectrometry, and fluorescence microscopy, we discovered that AβOs are indeed present in the developing retina, where multiple proteoforms are expressed in a highly regulated cell-specific manner. The expression of the AβO proteoforms was selectively associated with transiently expressed phosphorylated Tau (pTau) proteoforms that, like AβOs, are linked to Alzheimer’s disease (AD). To test whether the AβOs were functional in development, embryos were cultured ex ovo and then injected intravitreally with either a beta-site APP-cleaving enzyme 1 (BACE-1) inhibitor or an AβO-selective antibody to prematurely lower the levels of AβOs. The consequence was disrupted histogenesis resulting in dysplasia resembling that seen in various retina pathologies. We suggest the hypothesis that embryonic AβOs are a new type of short-lived peptidergic hormone with a role in neural development. Such a role could help explain why a peptide that manifests deleterious gain-of-function activity when it oligomerizes in the aging brain has been evolutionarily conserved.

show abstract

“…Alzheimer's disease has small and humble beginnings. This APP is expressed at particularly high levels in the cells of the brain, where it is thought to be important for neuronal growth, synapse maintenance, and memory formation (Mileusnic and Rose 2010). In the membrane, APP is content; it does its protein job and lives its protein life.…”

Section: Middletown Ct 17 Years Latermentioning

confidence: 99%

Narratives of Neurology: Exploring the Broken Brain Through Interview

Goodstein¹

View full text Add to dashboard Cite

show abstract

The Chick as a Model for the Study of the Cellular Mechanisms and Potential Therapies for Alzheimer's Disease

Cited by 5 publications

References 60 publications

Origins of Knowledge: Insights from Precocial Species

Origins of Knowledge: Insights from Precocial Species

An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis

Narratives of Neurology: Exploring the Broken Brain Through Interview

Contact Info

Product

Resources

About