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Title: Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID
Sustained cognitive deficits are a common and debilitating feature of “long COVID”, but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and executive functioning. COVID-19 infection greatly increases kynurenic acid (KYNA) and glutamate carboxypeptidase II (GCPII) in brain, both of which can be particularly deleterious to PFC function. KYNA blocks both NMDA and nicotinic-alpha-7 receptors, the two receptors required for dlPFC neurotransmission, and GCPII reduces mGluR3 regulation of cAMP-calcium-potassium channel signaling, which weakens dlPFC network connectivity and reduces dlPFC neuronal firing. Two agents approved for other indications may be helpful in restoring dlPFC physiology: the antioxidant N-acetyl cysteine inhibits the production of KYNA, and the α2A-adrenoceptor agonist guanfacine regulates cAMP-calcium-potassium channel signaling in dlPFC and is also anti-inflammatory. Thus, these agents may be helpful in treating the cognitive symptoms of long COVID.  more » « less
Award ID(s):
2015276
PAR ID:
10529584
Author(s) / Creator(s):
; ;
Publisher / Repository:
MDPI
Date Published:
Journal Name:
Neurology International
Volume:
15
Issue:
2
ISSN:
2035-8377
Page Range / eLocation ID:
725 to 742
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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