Aging-related neurodegeneration eliminates male courtship choice in Drosophila

Hu, Yujia; Han, Yi; Wang, Xingjun; Xue, Lei

doi:10.1016/j.neurobiolaging.2014.02.026

Cited by 17 publications

(39 citation statements)

References 19 publications

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“…Transient silencing of APPL in the mushroom bodies, the memory center of insects, demonstrated that it is specifically involved in long-term memory, which requires changes in synapse architecture (Goguel et al, 2011). In addition, APP overexpression in the courtship circuit decreased the preference of males to mate with younger females, but the total courtship remained the same, suggesting specific alterations in this circuit (Hu et al, 2014). These results support the hypothesis that APP function is critical to maintain synaptic activity, which could be relevant in AD.…”

Section: App Function and Processing In Drosophilamentioning

confidence: 98%

Modeling the complex pathology of Alzheimer's disease in Drosophila

Fernández-Fúnez

Mena

Rincón-Limas

2015

Experimental Neurology

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Alzheimer’s disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. AD is mostly a sporadic disorder and its main risk factor is age, but mutations in three genes that promote the accumulation of the amyloid-β (Aβ42) peptide revealed the critical role of Amyloid precursor protein (APP) processing in AD. Neurofibrillary tangles enriched in tau are the other pathological hallmark of AD, but the lack of causative tau mutations still puzzles researchers. Here, we describe the contribution of a powerful invertebrate model, the fruit fly Drosophila melanogaster, to uncovering the function and pathogenesis of human APP, Aβ42, and tau. APP and tau participate in many complex cellular processes, although their main function is microtubule stabilization and the to-and-fro transport of axonal vesicles. Additionally, expression of secreted Aβ42 induces prominent neuronal death in Drosophila, a critical feature of AD, making this model a popular choice for identifying intrinsic and extrinsic factors mediating Aβ42 neurotoxicity. Overall, Drosophila has made significant contributions to better understand the complex pathology of AD, although additional insight can be expected from combining multiple transgenes, performing genome-wide loss-of-function screens, and testing anti-tau therapies alone or in combination with Aβ42.

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Section: App Function and Processing In Drosophilamentioning

confidence: 98%

Modeling the complex pathology of Alzheimer's disease in Drosophila

Fernández-Fúnez

Mena

Rincón-Limas

2015

Experimental Neurology

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“…204 Understanding the nuances of specific courtship activities allows for a fine-tuned assessment of the effect of aging on this critical social behavior. 208,209 As males age, they lose their preference for young, virgin females, and have an overall reduction in courtship. Even magnetic fields have recently been shown to increase male courtship activity, 207 highlighting the breadth of sensitivity this behavior has to variation in conditions.…”

Section: Courtshipmentioning

confidence: 99%

“…Many internal (eg, female sexual maturity 205 ) and external (eg, environmental conditions 206 ) factors can influence courtship and receptivity, and studies on courtship activity need be mindful of these influences on behavior. [208][209][210][211] Male preference for young females is also eliminated with induced neurodegeneration, 39,210,212 suggesting that higherorder processes are involved in this preference. Courtship is affected by aging.…”

Section: Courtshipmentioning

confidence: 99%

Social behavior and aging: A fly model

Brenman-Suttner

Yost

Frame

et al. 2019

Genes Brain and Behavior

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The field of behavioral genetics has recently begun to explore the effect of age on social behaviors. Such studies are particularly important, as certain neuropsychiatric disorders with abnormal social interactions, like autism and schizophrenia, have been linked to older parents. Appropriate social interaction can also have a positive impact on longevity, and is associated with successful aging in humans. Currently, there are few genetic models for understanding the effect of aging on social behavior and its potential transgenerational inheritance. The fly is emerging as a powerful model for identifying the basic molecular mechanisms underlying neurological and neuropsychiatric disorders. In this review, we discuss these recent advancements, with a focus on how studies in Drosophila melanogaster have provided insight into the effect of aging on aspects of social behavior, including across generations.

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“…Since cognitive impairment is one of the major clinical characteristics of AD patients, we attempted to determine the role of CHIP in APP‐induced cognitive deficits. To this end, we first carried out the male courtship choice assays, in which male flies were provided with both younger and older virgin females simultaneously, and the courtship index (CI) was checked as previously described (Hu, Han, Han, Wang, & Xue, ). To accurately quantify the extent of males’ preference for younger or older females in courtship choice assay, we measured the preference index (PI) indicating a relative difference between males’ CI toward younger or older females (Hu et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…To this end, we first carried out the male courtship choice assays, in which male flies were provided with both younger and older virgin females simultaneously, and the courtship index (CI) was checked as previously described (Hu, Han, Han, Wang, & Xue, ). To accurately quantify the extent of males’ preference for younger or older females in courtship choice assay, we measured the preference index (PI) indicating a relative difference between males’ CI toward younger or older females (Hu et al, ). Consistent with the previous report (Hu et al, ), 3‐day‐old control males courted vigorously toward the younger females rather than the older ones (Figure c), indicating a courtship preference behavior for younger mates (Figure d).…”

Section: Resultsmentioning

confidence: 99%

CHIP modulates APP‐induced autophagy‐dependent pathological symptoms in Drosophila

et al. 2019

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Dysregulation of autophagy is associated with the neurodegenerative processes in Alzheimer's disease (AD), yet it remains controversial whether autophagy is a cause or consequence of AD. We have previously expressed the full‐length human APP in Drosophila and established a fly AD model that exhibits multiple AD‐like symptoms. Here we report that depletion of CHIP effectively palliated APP‐induced pathological symptoms, including morphological, behavioral, and cognitive defects. Mechanistically, CHIP is required for APP‐induced autophagy dysfunction, which promotes Aβ production via increased expression of BACE and Psn. Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.

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Aging-related neurodegeneration eliminates male courtship choice in Drosophila

Cited by 17 publications

References 19 publications

Modeling the complex pathology of Alzheimer's disease in Drosophila

Modeling the complex pathology of Alzheimer's disease in Drosophila

Social behavior and aging: A fly model

CHIP modulates APP‐induced autophagy‐dependent pathological symptoms in Drosophila

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