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10.1016/j.nlm.2020.107327 http://scihub22266oqcxt.onion/10.1016/j.nlm.2020.107327 33075480!7567669!33075480     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\33075480.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Neurobiol+Learn+Mem 2020 ; 176 (ä): 107327 Nephropedia Template TP {{tp|p=33075480|t=2020. Guanfacine s mechanism of action in treating prefrontal cortical disorders: Successful translation across species |pdf=|usr=}}{{33075480}} gab.com Text Guanfacine s mechanism of action in treating prefrontal cortical disorders: Successful translation across species JO: Neurobiol Learn Mem http://www.kidney.de/pget.php?&tw=1&pmid=33075480 #FOAvip The selective norepinephrine (NE) alpha2A-adrenoceptor (alpha2A-AR) agonist, guanfacine (Intuniv), is FDA-approved for treating Attention Deficit Hyperactivity Disorder (ADHD) based on research in animals, a translational success story. Guanfacine is also widely used off-label in additional mental disorders that involve impaired functioning of the prefrontal cortex (PFC), including stress-related disorders such as substance abuse, schizotypic cognitive deficits, and traumatic brain injury. The PFC subserves high order cognitive and executive functions including working memory, abstract reasoning, insight and judgment, and top-down control of attention, action and emotion. These abilities arise from PFC microcircuits with extensive recurrent excitation through NMDAR synapses. There is powerful modulation of these synapses, where cAMP-PKA opening of nearby potassium (K(+)) channels can rapidly and dynamically alter synaptic strength to coordinate arousal state with cognitive state, e.g. to take PFC "offline" during uncontrollable stress. A variety of evidence shows that guanfacine acts within the PFC via post-synaptic alpha2A-AR on dendritic spines to inhibit cAMP-PKA-K(+) channel signaling, thus strengthening network connectivity, enhancing PFC neuronal firing, and improving PFC cognitive functions. Although guanfacine's beneficial effects are present in rodent, they are especially evident in primates, where the PFC greatly expands and differentiates. In addition to therapeutic actions in PFC, stress-related disorders may also benefit from additional alpha2-AR actions, such as weakening plasticity in the amygdala, reducing NE release, and anti-inflammatory actions by deactivating microglia. Altogether, these NE alpha2-AR actions optimize top-down control by PFC networks, which may explain guanfacine's benefits in a variety of mental disorders. Twit Text FOAVip Guanfacine s mechanism of action in treating prefrontal cortical disorders: Successful translation across species ????Neurobiol Learn Mem http://www.kidney.de/pget.php?&tw=1&pmid=33075480 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33075480 #FOAvip English Wikipedia <ref>{{Cite pmid|33075480}}</ref> Guanfacine s mechanism of action in treating prefrontal cortical disorders: Successful translation across species #MMPMID33075480 Arnsten AFT Neurobiol Learn Mem 2020[Dec]; 176 (ä): 107327 PMID33075480show ga The selective norepinephrine (NE) alpha2A-adrenoceptor (alpha2A-AR) agonist, guanfacine (Intuniv), is FDA-approved for treating Attention Deficit Hyperactivity Disorder (ADHD) based on research in animals, a translational success story. Guanfacine is also widely used off-label in additional mental disorders that involve impaired functioning of the prefrontal cortex (PFC), including stress-related disorders such as substance abuse, schizotypic cognitive deficits, and traumatic brain injury. The PFC subserves high order cognitive and executive functions including working memory, abstract reasoning, insight and judgment, and top-down control of attention, action and emotion. These abilities arise from PFC microcircuits with extensive recurrent excitation through NMDAR synapses. There is powerful modulation of these synapses, where cAMP-PKA opening of nearby potassium (K(+)) channels can rapidly and dynamically alter synaptic strength to coordinate arousal state with cognitive state, e.g. to take PFC "offline" during uncontrollable stress. A variety of evidence shows that guanfacine acts within the PFC via post-synaptic alpha2A-AR on dendritic spines to inhibit cAMP-PKA-K(+) channel signaling, thus strengthening network connectivity, enhancing PFC neuronal firing, and improving PFC cognitive functions. Although guanfacine's beneficial effects are present in rodent, they are especially evident in primates, where the PFC greatly expands and differentiates. In addition to therapeutic actions in PFC, stress-related disorders may also benefit from additional alpha2-AR actions, such as weakening plasticity in the amygdala, reducing NE release, and anti-inflammatory actions by deactivating microglia. Altogether, these NE alpha2-AR actions optimize top-down control by PFC networks, which may explain guanfacine's benefits in a variety of mental disorders. |Adrenergic alpha-2 Receptor Agonists/*pharmacology/*therapeutic use[MESH] |Animals[MESH] |Attention Deficit Disorder with Hyperactivity/drug therapy[MESH] |Cognition Disorders/*drug therapy[MESH] |Cognition/*drug effects[MESH] |Guanfacine/*pharmacology/*therapeutic use[MESH] |Humans[MESH] |Macaca mulatta[MESH] |Memory, Short-Term/drug effects[MESH] |Mice[MESH] |Nerve Net/physiology[MESH] |Neurons/drug effects[MESH] |Prefrontal Cortex/*drug effects/physiology[MESH] |Rats[MESH]Guanfacine s mechanism of action in treating prefrontal cortical disor(epmc).pdf DeepDyve Pubget Overpricing