Down-regulation of dorsal striatal αCaMKII causes striatum-related cognitive and synaptic disorders

Wang, Qi; Yin, Pengcheng; Yu, Bin; Zhao, Zheng; Richter‐Levin, Gal; Yu, Lu; Cao, Xiaohua

doi:10.1016/j.expneurol.2017.09.004

Cited by 10 publications

(3 citation statements)

References 79 publications

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“…In the striatum, permanent inhibition of CaMKIIα expression after the stereotaxical injection of a lentivirus expressing a shRNA before training impaired accelerating rotarod and water cross maze test performances. However, these animals were able to learn properly after consecutive training similarly to what it has been seen for transgenic animals (Wang et al, 2017).…”

Section: Role Of α Isoform In Memorysupporting

confidence: 65%

CaMKII Isoforms in Learning and Memory: Localization and Function

Zalcman

Federman

Romano

2018

Front. Mol. Neurosci.

132

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Calcium/calmodulin-dependent protein kinase II (CaMKII) is a key protein kinase in neural plasticity and memory, as have been shown in several studies since the first evidence in long-term potentiation (LTP) 30 years ago. However, most of the studies were focused mainly in one of the four isoforms of this protein kinase, the CaMKIIα. Here we review the characteristics and the role of each of the four isoforms in learning, memory and neural plasticity, considering the well known local role of α and β isoforms in dendritic terminals as well as recent findings about the γ isoform as calcium signals transducers from synapse to nucleus and δ isoform as a kinase required for a more persistent memory trace.

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Section: Role Of α Isoform In Memorysupporting

confidence: 65%

CaMKII Isoforms in Learning and Memory: Localization and Function

Zalcman

Federman

Romano

2018

Front. Mol. Neurosci.

132

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“…One possible mechanism is through reducing calcium influx through voltage-dependent calcium channels because of a reduction in excitability ( Willett et al, 2020 ). This lower calcium would reduce the activation of calcium-dependent kinases critical for LTP, such as calcium/calmodulin-dependent protein kinase II (CaMKII; Q. Wang et al, 2017 ) and protein kinase C (PKC; Gubellini et al, 2004 ; Hawes et al, 2013 ). For more specific methods through which estradiol affects LTP, pathways activated by individual receptors, ERα and GPER, must be explored.…”

Section: Discussionmentioning

confidence: 99%

Estradiol Receptors Inhibit Long-Term Potentiation in the Dorsomedial Striatum

Lewitus,

Blackwell

2023

eNeuro

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Estradiol, a female sex hormone and the predominant form of estrogen, has diverse effects throughout the brain including in learning and memory. Estradiol modulates several types of learning that depend on the dorsomedial striatum (DMS), a subregion of the basal ganglia involved in goal-directed learning, cued action-selection, and motor skills. A cellular basis of learning is synaptic plasticity, and the presence of extranuclear estradiol receptors ERα, ERβ, and G protein-coupled estrogen receptor (GPER) throughout the DMS suggests that estradiol may influence rapid cellular actions including those involved in plasticity. To test whether estradiol affects synaptic plasticity in the DMS, corticostriatal long-term potentiation (LTP) was induced using theta-burst stimulation inex vivobrain slices from intact male and female C57BL/6 mice. Extracellular field recordings showed that female mice in the diestrus stage of the estrous cycle exhibited LTP similar to male mice, while female mice in estrus did not exhibit LTP. Furthermore, antagonists of ERα or GPER rescued LTP in estrus females and agonists of ERα or GPER reduced LTP in diestrus females. In males, activating ERα but not GPER reduced LTP. These results uncover an inhibitory action of estradiol receptors on cellular learning in the DMS and suggest a cellular mechanism underlying the impairment in certain types of DMS-based learning observed in the presence of high estradiol. Due to the dorsal striatum’s role in drug addiction, these findings may provide a mechanism underlying an estradiol-mediated progression from goal-directed to habitual drug use.Significance StatementThis study examined the role of the female reproductive cycle and female sex hormones in synaptic plasticity, a cellular process that underlies learning behavior, in a brain region involved in goal-directed learning. Synaptic plasticity was similar between male mice and female mice in the low estradiol phase of the cycle. In contrast, female mice in a high estradiol phase of the cycle did not exhibit synaptic plasticity. The effect of estradiol was mediated by two of the three estradiol receptors found in the brain. The results have implications for the role of the female reproductive cycle in the development of drug addiction, which involves a progression from goal-directed learning to habit-based learning as drug use switches from recreational to compulsive.

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“…Camk2n1 can prevent long-term memory loss (22). However, Camk2n1 is an inhibitor of CaMKII, which is necessary for motor learning and long-term potentiation (23). Interestingly, paracrine IL-6 upregulates Copb1 as part of the COPI complex.…”

Section: Discussionmentioning

confidence: 99%

Paracrine Interleukin 6 Induces Cerebral Remodeling at Early Stages After Unilateral Common Carotid Artery Occlusion in Mice

Kuffner

Koch

Kirchner

et al. 2022

Front. Cardiovasc. Med.

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AimsCarotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain. If no transient ischemic attack or stroke occur, it is classified asymptomatic. In the long-term, though, it can lead to cognitive impairment. Fostering cerebral remodeling after carotid artery occlusion might be a new concept of treatment. Paracrine Interleukin 6 (IL-6) can induce such remodeling processes at early stages. However, it has neurodegenerative long-term effects. With this exploratory study, we investigated the effect of paracrine IL-6 on cerebral remodeling in early stages after asymptomatic carotid artery occlusion to identify new treatment targets.Methods and ResultsTo mimic a human asymptomatic carotid artery disease, we used a mouse model of unilateral common carotid artery (CCA) occlusion. We developed a mouse model for inducible paracrine cerebral IL-6 expression (Cx30-Cre-ERT2;FLEX-IL6) and induced IL-6 2 days after CCA occlusion. We studied the effects of paracrine IL-6 after CCA occlusion on neuronal connectivity using diffusion tensor imaging and on local proteome regulations of the hypo-perfused striatum and contralateral motor cortex using mass spectrometry of laser capture micro-dissected tissues. Paracrine IL-6 induced cerebral remodeling leading to increased inter-hemispheric connectivity and changes in motor system connectivity. We identified changes in local protein abundance which might have adverse effects on functional outcome such as upregulation of Synuclein gamma (Sncg) or downregulation of Proline Dehydrogenase 1 (Prodh). However, we also identified changes in local protein abundance having potentially beneficial effects such as upregulation of Caprin1 or downregulation of GABA transporter 1 (Gat1).ConclusionsParacrine cerebral IL-6 at early stages induces changes in motor system connectivity and the proteome after asymptomatic CCA occlusion. Our results may help to distinguish unfavorable from beneficial IL-6 dependent protein regulations. Focusing on these targets might generate new treatments to improve long-term outcome in patients with carotid artery disease.

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Down-regulation of dorsal striatal αCaMKII causes striatum-related cognitive and synaptic disorders

Cited by 10 publications

References 79 publications

CaMKII Isoforms in Learning and Memory: Localization and Function

CaMKII Isoforms in Learning and Memory: Localization and Function

Estradiol Receptors Inhibit Long-Term Potentiation in the Dorsomedial Striatum

Paracrine Interleukin 6 Induces Cerebral Remodeling at Early Stages After Unilateral Common Carotid Artery Occlusion in Mice

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