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Signaling Mechanisms in Cognition
Author(s) -
Doursout Marie-Francoise,
Sundaresan Alamelu,
Ocampo Jessika Suescun,
Schiess Mya. C
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09755
Subject(s) - morris water navigation task , neuroscience , cognition , knockout mouse , gastrointestinal tract , mechanism (biology) , neuroinflammation , medicine , psychology , biology , inflammation , receptor , immunology , philosophy , epistemology
Signaling in the gastrointestinal tract is of great interest as a contributing factor to the development of cognition. The dysregulation of Gut‐Brain‐Axis (GBA) signaling may be associated with gastrointestinal manifestations preceding impairments in the cognitive and/or memory and learning process, supporting the hypothesis that it starts from the gut and spreads to the brain ( Braak et al. 2013). The overall goal of this project is to identify how the gut signals to the brain via gut‐synthesized molecules in relation to learning and memory. We suggest that α‐synuclein in the gut plays a key role in gut injury in response to lipopolysaccharide (LPS) and alcohol. Its aggregation possibly initiates the spreading of toxicity from the gut to the brain via the vagus nerve. This could cause an increase in hyper‐phosphorylated tau protein and repression of protective BDNF, leading to cognitive impairment. There are several highly innovative aspects of our proposal. Preliminary data showed increased α‐synuclein in LPS/alcohol injury in rodent models. Here, we propose to use a more sophisticated model: Wild Type (WT) and SNCA knockout (KO) mice treated and non‐treated with LPS/alcohol. Specifically, we will assess whether alterations of the intestinal barrier (or leaky guts) enhances damage as well as the increased production of α‐synuclein. The cognitive function test has been successfully performed using the Morris Water Maze (MWM) in murine model (APP‐mice). Since the mechanisms of GBA are still being worked out, the proposed objectives were to assess the time course and thereby threshold of the compromised intestinal barrier capable of influencing brain function, specifically cognitive and memory function in mice challenged with gut injury. Given the intense bidirectional interaction of the gut with the brain influencing neuronal activity, behavior (cognitive and memory), as well as levels of neurotrophic factors and inflammatory processes, the proposed studies may reshape our understanding of the etiology of cognitive and memory functions.Braak H1 , Del Tredici K , Rüb U , de Vos RA , Jansen Steur EN , Braak E . Staging of brain pathology related to sporadic Parkinson’s disease . Neurobiol Aging. 24 ( 2 ): 197 – 211 ; 2013 .