HIV-1 Tat-induced diarrhea evokes an enteric glia-dependent neuroinflammatory response in the central nervous system.

Abstract

Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associated gastrointestinal and neurological manifestations and key regulators of gut-brain signaling.

• Authors: Giuseppe Esposito, Elena Capoccia, Stefano Gigli, Marcella Pesce, Eugenia Bruzzese, Alessandra D'Alessandro, Carla Cirillo, Alessandro di Cerbo, Rosario Cuomo, Luisa Seguella, Luca Steardo, Giovanni Sarnelli
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 7735 (08 10 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28798420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Glial Fibrillary Acidic Protein
• S100 Calcium Binding Protein beta Subunit
• tat Gene Products, Human Immunodeficiency Virus

Topics

• Animals
• Biomarkers
• Central Nervous System (metabolism, pathology, physiopathology)
• Cerebral Cortex (metabolism, pathology, physiopathology)
• Cognition Disorders (etiology, metabolism, psychology)
• Diarrhea (etiology)
• Disease Models, Animal
• Enteric Nervous System (metabolism, physiopathology)
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis
• HIV Infections (complications, virology)
• Inflammation (etiology, metabolism)
• Male
• Neuroglia (metabolism)
• Rats
• S100 Calcium Binding Protein beta Subunit (metabolism)
• Spinal Cord (metabolism, pathology, physiopathology)
• tat Gene Products, Human Immunodeficiency Virus (adverse effects)