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1.
Nat Aging ; 4(4): 546-567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553564

RESUMO

Partial reprogramming (pulsed expression of reprogramming transcription factors) improves the function of several tissues in old mice. However, it remains largely unknown how partial reprogramming impacts the old brain. Here we use single-cell transcriptomics to systematically examine how partial reprogramming influences the subventricular zone neurogenic niche in aged mouse brains. Whole-body partial reprogramming mainly improves neuroblasts (cells committed to give rise to new neurons) in the old neurogenic niche, restoring neuroblast proportion to more youthful levels. Interestingly, targeting partial reprogramming specifically to the neurogenic niche also boosts the proportion of neuroblasts and their precursors (neural stem cells) in old mice and improves several molecular signatures of aging, suggesting that the beneficial effects of reprogramming are niche intrinsic. In old neural stem cell cultures, partial reprogramming cell autonomously restores the proportion of neuroblasts during differentiation and blunts some age-related transcriptomic changes. Importantly, partial reprogramming improves the production of new neurons in vitro and in old brains. Our work suggests that partial reprogramming could be used to rejuvenate the neurogenic niche and counter brain decline in old individuals.


Assuntos
Células-Tronco Neurais , Neurônios , Camundongos , Animais , Neurogênese/genética , Diferenciação Celular/genética , Reprogramação Celular/genética
2.
Endocrinology ; 162(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33834205

RESUMO

The paraventricular nucleus of the hypothalamus (PVH) is a heterogeneous collection of neurons that play important roles in modulating feeding and energy expenditure. Abnormal development or ablation of the PVH results in hyperphagic obesity and defects in energy expenditure whereas selective activation of defined PVH neuronal populations can suppress feeding and may promote energy expenditure. Here, we characterize the contribution of calcitonin receptor-expressing PVH neurons (CalcRPVH) to energy balance control. We used Cre-dependent viral tools delivered stereotaxically to the PVH of CalcR2Acre mice to activate, silence, and trace CalcRPVH neurons and determine their contribution to body weight regulation. Immunohistochemistry of fluorescently-labeled CalcRPVH neurons demonstrates that CalcRPVH neurons are largely distinct from several PVH neuronal populations involved in energy homeostasis; these neurons project to regions of the hindbrain that are implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. Acute activation of CalcRPVH neurons suppresses feeding without appreciably augmenting energy expenditure, whereas their silencing leads to obesity that may be due in part due to loss of PVH melanocortin-4 receptor signaling. These data show that CalcRPVH neurons are an essential component of energy balance neurocircuitry and their function is important for body weight maintenance. A thorough understanding of the mechanisms by which CalcRPVH neurons modulate energy balance might identify novel therapeutic targets for the treatment and prevention of obesity.


Assuntos
Metabolismo Energético/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Receptores da Calcitonina/fisiologia , Animais , Ingestão de Alimentos/fisiologia , Metabolismo Energético/genética , Comportamento Alimentar/fisiologia , Homeostase/fisiologia , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Receptor Tipo 4 de Melanocortina/fisiologia , Receptores da Calcitonina/genética , Receptores da Calcitonina/metabolismo
3.
Proc Biol Sci ; 288(1943): 20203010, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33468004

RESUMO

Most recognition is based on identifying features, but specialization for face recognition in primates relies on a different mechanism, termed 'holistic processing' where facial features are bound together into a gestalt which is more than the sum of its parts. Here, we test whether individual face recognition in paper wasps also involved holistic processing using a modification of the classic part-whole test in two related paper wasp species: Polistes fuscatus, which use facial patterns to individually identify conspecifics, and Polistes dominula, which lacks individual recognition. We show that P. fuscatus use holistic processing to discriminate between P. fuscatus face images but not P. dominula face images. By contrast, P. dominula do not rely on holistic processing to discriminate between conspecific or heterospecific face images. Therefore, P. fuscatus wasps have evolved holistic face processing, but this ability is highly specific and shaped by species-specific and stimulus-specific selective pressures. Convergence towards holistic face processing in distant taxa (primates, wasps) as well as divergence among closely related taxa with different recognition behaviour (P. dominula, P. fuscatus) suggests that holistic processing may be a universal adaptive strategy to facilitate expertise in face recognition.


Assuntos
Reconhecimento Facial , Vespas , Animais , Reconhecimento Psicológico , Especificidade da Espécie
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