Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice

Takahashi, Miyuki; Takasugi, Toshiyuki; Kawakami, Arisa; Wei, Ran; Ando, Kanae; Ohshima, Toshio; Hisanaga, Shin‐ichi

doi:10.1007/s11064-022-03642-9

Cited by 2 publications

(3 citation statements)

References 42 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Simhadri,

Rashid,

Karri

et al. 2024

Preprint

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Tau hyperphosphorylation at Ser396/404 and its adverse neurological effects have been evident in animal models of cerebral malaria (CM). As a counter measure, quest for novel pharmacological therapeutics to ameliorate tau hyperphosphorylation in neurodegeneration and restore behavioural and cognitive functions with high efficacy in CM has been at the forefront of neurobiological studies. In this study, using experimental model of cerebral malaria (ECM), we administered four different polycyclitol derivatives, SR4 (01-04) as an adjunctive to ARM therapy resulting in alleviation of cdk5/p25 based tau signaling cascade and restoration of long-term memory. Limitations of scyllo-inositol and rational to synthesize these polycyclitols efficiently has also been captured in the backdrop. Initially, we studied long-term, short term memory and novelty based learning by conducting Barnes maze, T-maze and novel object recognition task in treated animal groups. The cognitive outcomes of SR4-02 (15) and SR4-04 (18) treated groups exhibited better learning and memory compared to SR4-01 (16) and SR4-03 (17) groups. We further evaluated cdk5/p25 and tau phosphorylation protein expression using western blotting, immunohistochemistry and Golgi-cox staining to study neuronal arborization pattern. Immunohistochemical analysis of hippocampal and cortical tissue regions showed reduced phospho tau expression in SR4-03 (17) and SR4-04 (18) groups compared to CM group. Similarly, Golgi-cox images showed increased neuronal density in Cornus Ammonis (CA1) and CA3 regions of hippocampus and cortex of SR4-02 (15), SR4-03 (17) and SR4-04 (18) treated mice. Overall, based on our findings, polycyclitol derivatives have the potential to alleviate tau levels and restore cognition in ECM.

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Section: Discussionmentioning

confidence: 99%

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

Simhadri,

Rashid,

Karri

et al. 2024

Preprint

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“…Inhibition of the Cdk5/caspase-3 pathway by p5-TAT can also attenuate radiation-induced cognitive dysfunction (Zhang et al, 2021 ). Inhibition of Cdk5 activity ameliorates anxiety and depression in mice (Takahashi et al, 2022b ). Cdk5 is found to induce mitochondrial kinetic defects in optic neuropathy (Rong et al, 2020 ).…”

Section: Other Neurological Disordersmentioning

confidence: 99%

“…(Zhang et al, 2021). Inhibition of Cdk5 activity ameliorates anxiety and depression in mice (Takahashi et al, 2022b). Cdk5 is found to induce mitochondrial kinetic defects in optic neuropathy (Rong et al, 2020).…”

Section: Other Neurological Disordersmentioning

confidence: 99%

The role of Cdk5 in neurological disorders

Chen

et al. 2022

Front. Cell. Neurosci.

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Neurological disorders are a group of disorders with motor, sensory or cognitive damage, caused by dysfunction of the central or peripheral nervous system. Cyclin-dependent kinases 5 (Cdk5) is of vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration. However, when the nervous system is subject to pathological stimulation, aberrant activation of Cdk5 will induce abnormal phosphorylation of a variety of substrates, resulting in a cascade signaling pathway, and thus lead to pathological changes. Cdk5 is intimately related to the pathological mechanism of a variety of neurological disorders, such as A-β protein formation in Alzheimer’s disease, mitochondrial fragmentation in cerebral ischemia, and apoptosis of dopaminergic neurons in Parkinson’s disease. It is worth noting that Cdk5 inhibitors have been reported to have neuroprotective effects by inhibiting related pathological processes. Therefore, in this review, we will briefly introduce the physiological and pathological mechanisms of Cdk5 in the nervous system, focusing on the recent advances of Cdk5 in neurological disorders and the prospect of targeted Cdk5 for the treatment of neurological disorders.

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Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice

Cited by 2 publications

References 42 publications

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

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

The role of Cdk5 in neurological disorders

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