Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus

Ding, Xin; Zhang, Haibo; Qiu, Hui; Wen, Xin; Zhang, Longzhen

doi:10.1007/s00381-022-05646-w

“…Given that cranial irradiation is known to induce cognitive impairment (Ding et al, 2022; Krull et al, 2018; Makale et al, 2017) , we first evaluated whether cranial irradiation impaired cognitive function in mice. To assess the effect of IR on cognitive function, we exposed mice to IR.…”

Section: Resultsmentioning

confidence: 99%

PAK3 downregulation induces cognitive impairment following cranial irradiation

Lee

¹

,

Kang

²

,

Moon

³

et al. 2023

Preprint

0

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Cranial irradiation is used for prophylactic brain radiotherapy as well as treatment of primary brain tumors. Despite its high efficiency, it often induces unexpected side effects, including cognitive dysfunction. Herein, we observed that mice exposed to cranial irradiation exhibited cognitive dysfunction, including altered spontaneous behavior, decreased spatial memory, and reduced novel object recognition. Analysis of actin cytoskeleton revealed that ionizing radiation (IR) disrupted the filamentous/globular actin (F/G-actin) ratio and downregulated the actin turnover signaling pathway p21-activated kinase 3 (PAK3)-LIM kinase 1 (LIMK1)-cofilin. Furthermore, we found that IR could upregulate microRNA-206-3p (miR-206-3p) targeting PAK3. As the inhibition of miR-206-3p through antagonist (antagomiR), IR-induced disruption of PAK3 signaling is restored. In addition, intranasal administration of antagomiR-206-3p recovered IR-induced cognitive impairment in mice. Our results suggest that cranial irradiation-induced cognitive impairment could be ameliorated by regulating PAK3 through antagomiR-206-3p, thereby affording a promising strategy for protecting cognitive function during cranial irradiation, and promoting quality of life in patients with radiation therapy.

show abstract

PAK3 downregulation induces cognitive impairment following cranial irradiation

Lee,

Kang,

Moon

et al. 2023

eLife

0

View full text Add to dashboard Cite

Cranial irradiation is used for prophylactic brain radiotherapy as well as treatment of primary brain tumors. Despite its high efficiency, it often induces unexpected side effects, including cognitive dysfunction. Herein, we observed that mice exposed to cranial irradiation exhibited cognitive dysfunction, including altered spontaneous behavior, decreased spatial memory, and reduced novel object recognition. Analysis of actin cytoskeleton revealed that ionizing radiation (IR) disrupted the filamentous/globular actin (F/G-actin) ratio and downregulated the actin turnover signaling pathway p21-activated kinase 3 (PAK3)-LIM kinase 1 (LIMK1)-cofilin. Furthermore, we found that IR could upregulate microRNA-206-3p (miR-206-3p) targeting PAK3. As the inhibition of miR-206-3p through antagonist (antagomiR), IR-induced disruption of PAK3 signaling is restored. In addition, intranasal administration of antagomiR-206-3p recovered IR-induced cognitive impairment in mice. Our results suggest that cranial irradiation-induced cognitive impairment could be ameliorated by regulating PAK3 through antagomiR-206-3p, thereby affording a promising strategy for protecting cognitive function during cranial irradiation, and promoting quality of life in patients with radiation therapy.

show abstract

PAK3 downregulation induces cognitive impairment following cranial irradiation

Lee,

Kang,

Moon

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Cranial irradiation is used for prophylactic brain radiotherapy as well as treatment of primary brain tumors. Despite its high efficiency, it often induces unexpected side effects, including cognitive dysfunction. Herein, we observed that mice exposed to cranial irradiation exhibited cognitive dysfunction, including altered spontaneous behavior, decreased spatial memory, and reduced novel object recognition. Analysis of actin cytoskeleton revealed that ionizing radiation (IR) disrupted the filamentous/globular actin (F/G-actin) ratio and downregulated the actin turnover signaling pathway p21-activated kinase 3 (PAK3)-LIM kinase 1 (LIMK1)-cofilin. Furthermore, we found that IR could upregulate microRNA-206-3p (miR-206-3p) targeting PAK3. As the inhibition of miR-206-3p through antagonist (antagomiR), IR-induced disruption of PAK3 signaling is restored. In addition, intranasal administration of antagomiR-206-3p recovered IR-induced cognitive impairment in mice. Our results suggest that cranial irradiation-induced cognitive impairment could be ameliorated by regulating PAK3 through antagomiR-206-3p, thereby affording a promising strategy for protecting cognitive function during cranial irradiation, and promoting quality of life in patients with radiation therapy.

show abstract

Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus

Cited by 5 publications

References 35 publications

PAK3 downregulation induces cognitive impairment following cranial irradiation

PAK3 downregulation induces cognitive impairment following cranial irradiation

PAK3 downregulation induces cognitive impairment following cranial irradiation

PAK3 downregulation induces cognitive impairment following cranial irradiation

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