Role of cyclin‑dependent kinase 5 in early brain injury following experimental subarachnoid hemorrhage

Abstract

Increasing evidence indicates that early brain injury (EBI) can contribute to poor outcomes following subarachnoid hemorrhage (SAH), and is associated with apoptosis. Cyclin-dependent kinase 5 (Cdk5) is a key mediator of neuronal viability. The role of Cdk5 in several neurological disorders has been elucidated; however, its role in EBI after SAH remains unclear. The present study aimed to explore the involvement of Cdk5 in EBI after SAH. The expression levels of Cdk5, Cdk5 phosphorylated at Tyr15 (Cdk5-pTyr15) and p25 (a Cdk5 activator) were assessed by western blotting, and the cell distribution of Cdk5 was demonstrated by double immunofluorescence. The expression levels of caspase-3 and cytochrome c were evaluated by western blotting to assess the severity of neuronal apoptosis. Nissl and TUNEL staining experiments were performed to observe the effects of roscovitine, a Cdk5 inhibitor, on EBI following SAH. The results indicated that the expression levels of Cdk5, p25 and Cdk5-pTyr15 significantly increased in the rat temporal cortex following SAH. Immunofluorescence staining indicated that Cdk5 was expressed in the neurons and astrocytes of the rat cortex after SAH and that Cdk5 underwent nuclear translocation in neurons. Roscovitine administration effectively inhibited Cdk5 activation. In conclusion, roscovitine treatment significantly mitigated EBI and alleviated cerebral edema following SAH. These findings suggest that Cdk5 is an important target in SAH therapy.

Polycyclitol derivatives restore long-term memory by regulating cdk5/p25 based tau signaling in experimental cerebral malaria

“…Tau phosphorylation at Ser396 is considered as the earliest event in Alzheimer's disease in which cdk5 has been implicated as potential candidate kinase (Mondragón-Rodríguez et al, 2014;Noble et al, 2003). Similarly, cdk5/p25 signaling is detected early in neurodegenerative diseases like Parkinson's (Ao et al, 2022), amylotrophic lateral sclerosis (ALS) (Bk et al, 2019), brain injuries like subarachnoid haemorrhage (Ding et al, 2022), anxiety, depression (Takahashi et al, 2022), learning disabilities involving cognitive impairment (Kamiki et al, 2018) and cancers like glioblastoma (GBM) (Peyressatre et al, 2020). Several research studies have shown that inhibition of hyperactivated cdk5 based signaling improved hippocampal neurogenesis and restored cognitive functions in radiation induced cognitive dysfunction (Zhang et al, 2021).…”

The role of Cdk5 in neurological disorders

“…Cdk5 has been proved to play a key role in many other neurological diseases, such as ALS (Bk et al, 2019 ), early brain injury (Ding et al, 2022 ), cerebral amyloidosis (Kiss et al, 2020 ), fragile X-associated tremor/ataxia syndrome (FXTAS; Robin et al, 2017 ), spinal muscular atrophy (Tejero et al, 2020 ), and systemic sclerosis (Wei et al, 2017 ). Circadian behavior (Zhou et al, 2022 ), learning disabilities (Kamiki et al, 2018 ), and aging (Spurrier et al, 2018 ) are also closely related to Cdk5.…”