GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.

Min Song,Daniel L Kaufman,Blake Middleton,Jide Tian,Cuong Q Nguyen

doi:10.3390/biomedicines10010129

Min Song, Daniel L Kaufman + Show 3 more

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https://doi.org/10.3390/biomedicines10010129

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Abstract

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the salivary and lachrymal glands resulting in oral and ocular dryness. There are no clinically approved therapies to slow the progression of SS. Immune cells possess receptors for the neurotransmitter GABA (GABA-Rs) and their activation has immunoregulatory actions. We tested whether GABA administration has potential for amelioration of SS in NOD.B10-H2b and C57BL/6.NOD-Aec1Aec2 mice, two spontaneous SS models. Oral GABA treatment was initiated (1) after the development of sialadenitis but before the onset of overt symptoms, or (2) after the appearance of overt symptoms. When assessed weeks later, GABA-treated mice had greater saliva and tear production, as well as quicker times to salvia flow, in both SS mouse models. This was especially evident when GABA treatment was initiated after the onset of overt disease. This preservation of exocrine function was not accompanied by significant changes in the number or area of lymphocytic foci in the salivary or lachrymal glands of GABA-treated mice and we discuss the possible reasons for these observations. Given that GABA-treatment preserved saliva and tear production which are the most salient symptoms of SS and is safe for consumption, it may provide a new approach to help ameliorate SS.

Highlights

Sjögren’s syndrome (SS) is a complex chronic autoimmune disease characterized by immune cell infiltration into exocrine glands, the salivary and lacrimal glands, which leads to a severe loss of secretory function and consequent xerostomia and keratoconjunctivitis sicca [1,2,3,4]
Prophylactic GABA Treatment in nonobese diabetic (NOD).B10-H2b Mice In NOD.B10-H2b mice, sialadenitis becomes histologically observable beginning at about 12 weeks in age and overt clinical symptoms such as reduced saliva and tear production are apparent by 24 weeks in age [43,44,45,46]
We observed that GABA-treated NOD.B10-H2b mice produced an average of 41% more saliva than the NOD.B10-H2b mice given plain water this was not statistically significant (Figure 1A)

Summary

Introduction

Sjögren’s syndrome (SS) is a complex chronic autoimmune disease characterized by immune cell infiltration into exocrine glands, the salivary and lacrimal glands, which leads to a severe loss of secretory function and consequent xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes) [1,2,3,4]. The underlying etiology of SS is thought to be heterogeneous and remains elusive but is thought to involve abnormal salivary gland homeostasis and progressive tissue damage by infiltrating immune cells and autoantibodies. Analysis of human salivary glands and experimental mouse models of SS reveals that focal lymphocytic infiltrates are dominated by CD4+ T cells with B cells and macrophages increasing with disease progression [6,7,8,9,10,11,12]. Several types of autoantibodies are associated with the development and progression of SS, including anti-nuclear, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-M3R autoantibodies [19]

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