Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model

Choi, Se Hoon; Bylykbashi, Enjana; Chatila, Zena K.; Lee, Star W.; Pulli, Benjamin; Clemenson, Gregory D.; Kim, Eun‐Hee; Rompala, Alexander; Oram, Mary K.; Asselin, Caroline; Aronson, Jenna; Zhang, Can; Miller, Sean; Lesinski, Andrea N.; Chen, John W.; Kim, Doo Yeon; Praag, Henriette van; Spiegelman, Bruce M.; Gage, Fred H.; Tanzi, Rudolph E.

doi:10.1126/science.aan8821

Cited by 590 publications

(505 citation statements)

References 59 publications

Supporting

Mentioning

439

Contrasting

Unclassified

Order By: Relevance

“…For example, activation of endogenous neural stem cells by Ascl1 oscillations can generate many new neurons, which may ameliorate neurodegenerative diseases such as Alzheimer disease and Huntington disease (Benraiss et al, 2013;Choi et al, 2018). For example, activation of endogenous neural stem cells by Ascl1 oscillations can generate many new neurons, which may ameliorate neurodegenerative diseases such as Alzheimer disease and Huntington disease (Benraiss et al, 2013;Choi et al, 2018).…”

Section: Con Clus Ionsmentioning

confidence: 99%

Regulation of active and quiescent somatic stem cells by Notch signaling

Sueda

Kageyama

2019

Dev Growth Differ

View full text Add to dashboard Cite

Somatic stem/progenitor cells actively proliferate and give rise to different types of mature cells (active state) in embryonic tissues while they are mostly dormant (quiescent state) in many adult tissues. Notch signaling is known to regulate both active and quiescent states of somatic stem cells, but how it regulates these different states is unknown. Recent studies revealed that the Notch effector Hes1 is expressed differently during the active and quiescent states during neurogenesis and myogenesis: high in the quiescent state and oscillatory in the active state. When the Hes1 expression level is high, both Ascl1 and MyoD expression are continuously suppressed. By contrast, when Hes1 expression oscillates, it periodically represses expression of the neurogenic factor Ascl1 and the myogenic factor MyoD, thereby driving Ascl1 and MyoD oscillations. High levels of Hes1 and the resultant Ascl1 suppression promote the quiescent state of neural stem cells, while Hes1 oscillation‐dependent Ascl1 oscillations regulate their active state. Similarly, in satellite cells of muscles, known adult muscle stem cells, high levels of Hes1 and the resultant MyoD suppression seem to promote their quiescent state, while Hes1 oscillation‐dependent MyoD oscillations activate their proliferation and differentiation. Therefore, the expression dynamics of Hes1 is a key regulatory mechanism of generating and maintaining active/quiescent stem cell states.

show abstract

Section: Con Clus Ionsmentioning

confidence: 99%

Regulation of active and quiescent somatic stem cells by Notch signaling

Sueda

Kageyama

2019

Dev Growth Differ

View full text Add to dashboard Cite

show abstract

“…BDNF, a downstream gene of cAMP signaling, mediated by CREB, is a well‐known regulator in modulating synaptic transmission and plasticity, memory development, and storage . It is also well established to have properties of antagonizing neuronal apoptosis .…”

Section: Discussionmentioning

confidence: 99%

“…These processes have been demonstrated as important for the induction and persistence of long‐term memory and long‐term potentiation . In addition, the pCREB can also regulate the expression of downstream apoptosis‐associated proteins, including Bcl‐2, Bax, caspase‐3, caspase‐8, and brain‐derived neurotrophic factor (BDNF), which have been found to promote the apoptosis of neurons, and share an association with aggravating cognitive dysfunction . Our previous studies showed that Mn exposure impaired hippocampus‐dependent cognitive function and reduced cAMP signaling and the protein levels of BDNF in occupational Mn‐exposed workers and chronic Mn‐treated rats .…”

Section: Introductionmentioning

confidence: 99%

Pivotal role of cAMP‐PKA‐CREB signaling pathway in manganese‐induced neurotoxicity in PC12 cells

Yang

Ma²,

Wei

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

Manganese (Mn) plays a critical role in individual growth and development, yet excessive exposure can result in neurotoxicity, especially cognitive impairment. Neuronal apoptosis is considered as one of the mechanisms of Mn‐induced neurotoxicity. Recent evidence suggests that cAMP‐PKA‐CREB signaling regulates apoptosis and is associated with cognitive function. However, whether this pathway participates in Mn‐induced neurotoxicity is not completely understood. To fill this gap, in vitro cultures of PC12 cells were exposed to 0, 400, 500, and 600 μmol/L Mn for 24 hours, respectively. Another group of cells were pretreated with 10.0 μmol/L rolipram (a phosphodiesterase‐4 [PDE4] inhibitor) for 1 hour followed by 500 μmol/L Mn exposure for 24 hours. Flow cytometry, immunofluorescence staining, enzyme‐linked immunosorbent assay, and Western blot analysis were used to detect the apoptosis rate, protein levels of PDE4, cAMP signaling, and apoptosis‐associated proteins, respectively. We found that Mn exposure significantly inhibited cAMP signaling and protein expression of Bcl‐2, while increasing apoptosis rate, protein levels of PDE4, Bax, activated caspase‐3, and activated caspase‐8 in PC12 cells. Pretreatment of rolipram ameliorated Mn‐induced deficits in cAMP signaling and apoptosis. These findings demonstrate that cAMP‐PKA‐CREB signaling pathway‐induced apoptosis is involved in Mn‐induced neurotoxicity.

show abstract

“…Different exercises are believed to be accompanied by distinct activities of sensory motor circuits to affect neuronal plasticity. Furthermore, there is accumulating evidence that different types of physical exercises such as forced and voluntary running can affect recovery from motor or memory dysfunction (Choi et al, ; Cotman, Berchtold, & Christie, ; So et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, there is accumulating evidence that different types of physical exercises such as forced and voluntary running can affect recovery from motor or memory dysfunction (Choi et al, 2018;Cotman, Berchtold, & Christie, 2007;So et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Different exercises can modulate the differentiation/maturation of neural stem/progenitor cells after photochemically induced focal cerebral infarction

et al. 2020

View full text Add to dashboard Cite

Introduction Exercise therapies during rehabilitation significantly promote recovery from various deficits after cerebral infarction, which is mediated by neuronal plasticity with distinct inputs. Although adult neurogenesis can also be modulated by neuronal activity before synaptogenesis, how distinct exercises contribute to the neurological reorganization of the injured cerebral cortex remains unclear. In the present study, we aimed to elucidate the effects of different exercise therapies on motor recovery and neuronal reorganization after photochemically induced focal cerebral infarction. Methods Here, we examined the effects of three different exercises—(a) forced lower‐intensity and (b) higher‐intensity treadmill exercises, and (c) voluntary exercise with wheel running—on motor recovery and adult neurogenesis in a rat model of focal cerebral infarction. Photochemically induced thrombosis (PIT) was used to generate focal infarction in rats that was mostly confined to their motor cortices. Results Beam walking tests showed that recovery after PIT‐induced cortical infarction differed in acute and chronic stages and was influenced by the type of exercise. Furthermore, forced low‐intensity training had more positive effects on functional recovery than other exercises or control. To evaluate the production of newly generated cells including de novo neurogenesis, we performed lineage analysis with BrdU labeling and immunofluorescence experiments. Lower‐intensity treadmill exercise increased the number of BrdU/NeuN colabeled cells, but not total BrdU‐retaining or BrdU/Sox2‐colabeled cells, in the peri‐infarct region of the ipsilateral cortex. In contrast, high‐intensity treadmill or voluntary exercises had the opposite effects. Conclusions These results suggest that neuronal maturation can be differently modulated by distinct exercises and that low‐intensity treadmill exercise could result in more potent generation of mature neurons. This also suggests the possibility that the generation of neural stem/progenitor cells and differentiation might be modulated by rehabilitation‐mediated neural plasticity.

show abstract

Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model

Cited by 590 publications

References 59 publications

Regulation of active and quiescent somatic stem cells by Notch signaling

Regulation of active and quiescent somatic stem cells by Notch signaling

Pivotal role of cAMP‐PKA‐CREB signaling pathway in manganese‐induced neurotoxicity in PC12 cells

Different exercises can modulate the differentiation/maturation of neural stem/progenitor cells after photochemically induced focal cerebral infarction

Contact Info

Product

Resources

About