Adult neurogenic process in the subventricular zone‐olfactory bulb system is regulated by Tau protein under prolonged stress

Dioli, Chrysoula; Patrício, Patrícia; Marie, Clemence; Morais, Mónica; Vyas, Sheela; Bessa, João M.; Pinto, Luísa; Sotiropoulos, Ioannis

doi:10.1111/cpr.13027

Cited by 7 publications

(4 citation statements)

References 85 publications

(142 reference statements)

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“…Further, the observation that the treatment of depression by antidepressants depends on an increased rate of neurogenesis also corroborates the key role of adult neurogenesis on this type of neurological disorder [ 59 ]. Although the majority of studies reporting a role for adult neurogenesis and stress resilience have been performed in hippocampal neurogenic niches, it has been already shown that the adult SVZ neurogenic process is also compromised under unpredicted prolonged stress [ 60 , 61 ]. Curiously, it has been recently demonstrated that both anxiety- and depression-like states lead to marked olfactory deficits along with impaired adult neurogenesis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

Santos

Moreira

Costa

et al. 2021

Cells

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Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.

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Section: Discussionmentioning

confidence: 99%

The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

Santos

Moreira

Costa

et al. 2021

Cells

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“…Tauopathy mice showed a decrease in the proliferation of adult NSCs in the SVZ from 2 months of age ( Komuro et al, 2015 ). Although tau plays a key role in the impairment of SVZ neuronal proliferation and migration under conditions such as chronic stress ( Dioli et al, 2021 ), its effect on adult SVZ neurogenesis in AD remains unclear. Finally, dysfunction of subependymal lipid metabolism plays a critical role in the deficits of adult SVZ neurogenesis in the early stage of AD via hyperactivation of the protein kinase B signaling pathway ( Gontier et al, 2015 ; Scopa et al, 2020 ).…”

Section: Subventricular Zone Neurogenesis In Alzheimer’s Diseasementioning

confidence: 99%

Relationship between adult subventricular neurogenesis and Alzheimer’s disease: Pathologic roles and therapeutic implications

Kim

Shin

Kim

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by irreversible cognitive declines. Senile plaques formed by amyloid-β (Aβ) peptides and neurofibrillary tangles, consisting of hyperphosphorylated tau protein accumulation, are prominent neuropathological features of AD. Impairment of adult neurogenesis is also a well-known pathology in AD. Adult neurogenesis is the process by which neurons are generated from adult neural stem cells. It is closely related to various functions, including cognition, as it occurs throughout life for continuous repair and development of specific neural pathways. Notably, subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, transports neurons to several brain regions such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. These migrating neurons can affect cognitive function and behavior in different neurodegenerative diseases. Despite several studies indicating the importance of adult SVZ neurogenesis in neurodegenerative disorders, the pathological alterations and therapeutic implications of impaired adult neurogenesis in the SVZ in AD have not yet been fully explained. In this review, we summarize recent progress in understanding the alterations in adult SVZ neurogenesis in AD animal models and patients. Moreover, we discuss the potential therapeutic approaches for restoring impaired adult SVZ neurogenesis. Our goal is to impart to readers the importance of adult SVZ neurogenesis in AD and to provide new insights through the discussion of possible therapeutic approaches.

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“…Protection in tau-KO mice is associated with reduced neuronal excitability [ 47 , 48 ], albeit long-term hippocampal potentiation and long-term depression are variable depending on the tau-KO strain [ 49 , 50 , 51 ]. The role of tau is also manifested in the modulation of adult neurogenesis in the hippocampus, olfactory bulb, and subventricular region under prolonged stress [ 52 , 53 ]. Tau deletion also prevents stress-induced dendritic atrophy [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

Deregulated Transcription and Proteostasis in Adult mapt Knockout Mouse

Andrés‐Benito

Flores

Busquet-Areny

et al. 2023

IJMS

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Transcriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas recognition memory remained unaltered. Cortical transcriptomic analysis revealed 69 downregulated and 105 upregulated genes in tau-KO mice, corresponding to synaptic structures, neuron cytoskeleton and transport, and extracellular matrix components. RT-qPCR validated increased mRNA levels of col6a4, gabrq, gad1, grm5, grip2, map2, rab8a, tubb3, wnt16, and an absence of map1a in tau-KO mice compared with WT mice. A few proteins were assessed with Western blotting to compare mRNA expression with corresponding protein levels. Map1a mRNA and protein levels decreased. However, β-tubulin III and GAD1 protein levels were reduced in tau-KO mice. Cortical phosphoproteomics revealed 121 hypophosphorylated and 98 hyperphosphorylated proteins in tau-KO mice. Deregulated phosphoproteins were categorized into cytoskeletal (n = 45) and membrane proteins, including proteins of the synapses and vesicles, myelin proteins, and proteins linked to membrane transport and ion channels (n = 84), proteins related to DNA and RNA metabolism (n = 36), proteins connected to the ubiquitin-proteasome system (UPS) (n = 7), proteins with kinase or phosphatase activity (n = 21), and 22 other proteins related to variegated pathways such as metabolic pathways, growth factors, or mitochondrial function or structure. The present observations reveal a complex altered brain transcriptome and phosphoproteome in tau-KO mice with only mild behavioral alterations.

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Adult neurogenic process in the subventricular zone‐olfactory bulb system is regulated by Tau protein under prolonged stress

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 85 publications

The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

Relationship between adult subventricular neurogenesis and Alzheimer’s disease: Pathologic roles and therapeutic implications

Deregulated Transcription and Proteostasis in Adult mapt Knockout Mouse

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