Antibiotic Treatment Attenuates Behavioral and Neurochemical Changes Induced by Exposure of Rats to Group A Streptococcal Antigen

Abstract

Post-streptococcal A (GAS) sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats) and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control) did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter’s possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.

Acute rheumatic fever and rheumatic heart disease

“…A study using the rat model has also addressed the effects of antibiotic therapy on behaviour and neurochemical changes. In this study, ampicillin treatment prevented the emergence of the motor symptoms and some of the behavioural alterations that were induced by GAS antigen exposure 100 .…”

Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond

“…, Lotan et al . ,b). These animal models include streptococcal exposure and immunization which led to the production of antibodies that deposited in the brain and also led to movement and neuropsychiatric symptoms in the mice or rats.…”

Gut microbiota: Implications in Parkinson's disease

“…Amp treatment prevented motor and behavioral impairments in mice exposed to Group A streptococci (GAS) antigen, which is responsible for the dysfunction of the central dopaminergic system. Amp increased the level of tyrosine hydroxylase, D1 and D2 receptors in the striatum, without any reduction in the levels of anti-GAS antibodies [49]. Since the central dopaminergic system is highly dysregulated in PD it could be possible that amp could exert its effect via modulating GM and GMBA.…”