Kapβ2 Inhibits Perioperative Neurocognitive Disorders in Rats with Mild Cognitive Impairment by Reversing the Nuclear-Cytoplasmic Mislocalization of hnRNPA2/B1

Miao Zhang; Feiyu Jia; Qiang Wang; Chenyi Yang; Xinyi Wang; Tianyue Liu; Qingkai Tang; Zhuo Yang; Haiyun Wang

doi:10.1007/s12035-023-03789-8

Kapβ2 Inhibits Perioperative Neurocognitive Disorders in Rats with Mild Cognitive Impairment by Reversing the Nuclear-Cytoplasmic Mislocalization of hnRNPA2/B1

Mol Neurobiol. 2023 Dec 16. doi: 10.1007/s12035-023-03789-8. Online ahead of print.

Authors

Miao Zhang^#^{1

2

3}, Feiyu Jia^#^{1

2

3}, Qiang Wang^#^{1

2

3}, Chenyi Yang², Xinyi Wang², Tianyue Liu², Qingkai Tang², Zhuo Yang⁴, Haiyun Wang^{5

6

7}

Affiliations

¹ The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
² Nankai University Affinity the Third Central Hospital, Tianjin, China.
³ Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin, China.
⁴ College of Medicine, Nankai University, Tianjin, China. zhuoyang@nankai.edu.cn.
⁵ The Third Central Clinical College of Tianjin Medical University, Tianjin, China. why819@126.com.
⁶ Nankai University Affinity the Third Central Hospital, Tianjin, China. why819@126.com.
⁷ Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin, China. why819@126.com.

^# Contributed equally.

PMID: 38102516
DOI: 10.1007/s12035-023-03789-8

Abstract

Harmful stimuli trigger mutations lead to uncontrolled accumulation of hnRNPA2/B1 in the cytoplasm, exacerbating neuronal damage. Kapβ2 mediates the bidirectional transport of most substances between the cytoplasm and the nucleus. Kapβ2 guides hnRNPA2/B1 back into the nucleus and restores its function, alleviating related protein toxicity. Here, we aim to explore the involvement of Kapβ2 in neurodegeneration in rats with MCI following sevoflurane anesthesia and surgery. Firstly, novel object recognition test and Barnes maze were conducted to assess behavioral performances, and we found Kapβ2 positively regulated the recovery of memory and cognitive function. In vivo electrophysiological experiments revealed that the hippocampal theta rhythm energy distribution was disrupted, coherence was reduced, and long-term potentiation was attenuated in MCI rats. LTP was greatly improved with positive modulation of Kapβ2. Next, functional MRI and BOLD imaging will be employed to examine the AFLL and FC values of dynamic connectivity between the cortex and hippocampus of the brain. The findings show that regulating Kapβ2 in the hippocampus region enhances functional activity and connections between brain regions in MCI rats. WB results showed that increasing Kapβ2 expression improved the expression and recovery of cognitive-related proteins in the hippocampus of MCI rats. Finally, WB and immunofluorescence were used to examine the changes in hnRNPA2/B1 expression in the nucleus and cytoplasm after overexpression of Kapβ2, and it was found that nucleocytoplasmic mis location was alleviated. Overall, these data show that Kapβ2 reverses the nucleoplasmic misalignment of hnRNPA2/B1, which slows neurodegeneration towards dementia in MCI after sevoflurane anesthesia and surgery. Our findings may lead to new approaches for perioperative neuroprotection of MCI patients.

Keywords: Heterogeneous nuclear ribonucleoprotein A2/B1; Karyopherin-β2; Mild cognitive impairment; Neurological protection; Perioperative.

Abstract

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