مورد إلكتروني
PDE2A Inhibition Enhances Axonal Sprouting, Functional Connectivity, and Recovery after Stroke.
| العنوان: | PDE2A Inhibition Enhances Axonal Sprouting, Functional Connectivity, and Recovery after Stroke. |
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| المؤلفون: | Bechay, Kirollos Raouf |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience; vol 42, iss 44, 8225-8236; 0270-6474 |
| بيانات النشر: | eScholarship, University of California 2022-11-01 |
| تفاصيل مُضافة: | Bechay, Kirollos Raouf Abduljawad, Nora Latifi, Shahrzad Suzuki, Kazunori Iwashita, Hiroki Carmichael, S Thomas |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Phosphodiesterase (PDE) inhibitors have been safely and effectively used in the clinic and increase the concentration of intracellular cyclic nucleotides (cAMP/cGMP). These molecules activate downstream mediators, including the cAMP response element-binding protein (CREB), which controls neuronal excitability and growth responses. CREB gain of function enhances learning and allocates neurons into memory engrams. CREB also controls recovery after stroke. PDE inhibitors are linked to recovery from neural damage and to stroke recovery in specific sites within the brain. PDE2A is enriched in cortex. In the present study, we use a mouse cortical stroke model in young adult and aged male mice to test the effect of PDE2A inhibition on functional recovery, and on downstream mechanisms of axonal sprouting, tissue repair, and the functional connectivity of neurons in recovering cortex. Stroke causes deficits in use of the contralateral forelimb, loss of axonal projections in cortex adjacent to the infarct, and functional disconnection of neuronal networks. PDE2A inhibition enhances functional recovery, increases axonal projections in peri-infarct cortex, and, through two-photon in vivo imaging, enhances the functional connectivity of motor system excitatory neurons. PDE2A inhibition after stroke does not have an effect on other aspects of tissue repair, such as angiogenesis, gliogenesis, neurogenesis, and inflammatory responses. These data suggest that PDE2A inhibition is an effective therapeutic approach for stroke recovery in the rodent and that it simultaneously enhances connectivity in peri-infarct neuronal populations.SIGNIFICANCE STATEMENT Inhibition of PDE2A enhances motor recovery, axonal projections, and functional connectivity of neurons in peri-infarct tissue. This represents an avenue for a pharmacological therapy for stroke recovery. |
| مصطلحات الفهرس: | Motor Neurons, Animals, Mice, Infarction, Phosphodiesterase Inhibitors, Recovery of Function, Male, Cyclic AMP Response Element-Binding Protein, Stroke, Cyclic Nucleotide Phosphodiesterases, Type 2, Neurogenesis, GCaMP, functional connectivity, neural repair, neurogenesis, phosphodiesterase, two photon, Neurosciences, Rehabilitation, Aging, Brain Disorders, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, Neurological, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf The Journal of neuroscience : the official journal of the Society for Neuroscience vol 42, iss 44, 8225-8236 0270-6474 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt2vs2c04t qt2vs2c04t https://escholarship.org/uc/item/2vs2c04t https://escholarship.org/ 1391587170 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1391587170 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |