Implications of Neuroinvasive Bacterial Peptides on Rodents Behaviour and Neurotransmission.

Aneela Taj,Nusrat Jamil

doi:10.3390/pathogens6030027

Abstract

Neuroinvasive microbes are capable of applying their influences on the autonomic nervous system (ANS) of the host followed by the involvement of central nervous system (CNS) by releasing extracellular metabolites that may cause alterations in the biochemical and neurophysiological environment. Consequently synaptic, neuroendocrine, peripheral immune, neuro-immune, and behavioural responses of the host facilitate the progression of infection. The present study was designed to extrapolate the effects of crude and purified extracellular peptides of neuropathogenic bacteria on behavioural responses and neurotransmission of Sprague Dawley (SD) models. Listeria monocytogenes (Lm) and Neisseria meningitides (Nm) were isolated from the 92 cerebrospinal fluid (CSF) samples collected from mentally compromised patients. Bacillus cereus (Bc) and Clostridium tetani (Ct) were also included in the study. All bacterial strains were identified by the standard biochemical procedures. Filter sterilized cell free cultural broths (SCFBs) were prepared of different culture media. Behavioural study and neurotransmitter analysis were performed by giving an intraperitoneal (i.p.) injection of each bacterial SCFB to four groups (Test; n = 7) of SD rats, whereas two groups each (Control; n = 7) received a nutrient broth (NB) control and sterile physiological saline control, respectively. Extracellular bioactive peptides of these bacteria were screened and purified. All experiments were repeated using purified bacterial peptides on SD rat cohorts. Our study indicated promising behavioural changes, including fever, swelling, and hind paw paralysis, in SD rat cohorts. Purified bacterial peptides of all bacteria used in the present study elicited marked changes in behaviour through the involvement of the autonomic nervous system. Furthermore, these peptides of meningitis bacteria were found to potently affect the dopaminergic neurotransmission in CNS.

Highlights

Microbial invasion of the central nervous system (CNS) has been proved to be the most severe and frequently fatal event during the course of many infectious diseases [1,2,3]
This experiment was delineated to evaluate the influence of filter sterilized cell free cultural broth (SCFB) of neuropathogenic bacteria on the physiological responses evoked in Sprague Dawley (SD) rats
Listeria monocytogenes (Lm)(SCFB) caused a curled body posture in rats (Figure 1C) and intense piloerection was observed subsequent to the exposure with Bacillus cereus (Bc)(SCFB) (Figure 1D)

Summary

Introduction

Microbial invasion of the central nervous system (CNS) has been proved to be the most severe and frequently fatal event during the course of many infectious diseases [1,2,3]. Diversified clinical manifestations, i.e., from viral encephalitis to bacterial meningitis occur [4,5,6,7,8,9,10]. Bacterial meningitis is established to be the most studied amongst the CNS invasions to date [11,12,13]. Experimental studies have amplified the understanding that meningitis associated brain injury and neuronal death is not mediated by the presence of viable bacteria. By contrast, it occurs as a consequence of the host reaction to a wide range of bacterial components and/or molecules [2,14,15]. Lipopolysaccharide (LPS) [16,17,18,19,20], peptidoglycan (PG) [21,22], exotoxins [23], and capsular polysaccharide [24] have been extensively evidenced to enhance

Methods

Results

Discussion

Conclusion