EFFECTS OF INTRANASAL BACTERIAL ENDOTOXIN ADMINISTRATION ON EXPRESSION OF ALPHA-SYNUCLEIN IN PERIPHERAL STRUCTURES OF THE OLFACTORY SYSTEM

Abstract

The involvement of olfactory dysfunction led to the proposal of ‘the olfactory vector hypothesis’ to explain both olfactory losses and the etiology of idiopathic Parkinson disease (PD) as a result of the transit of an environmental virus or chemical agent that enters the central nervous system (CNS) via the nose, activating the glial response of the brain that may lead to dopamine neuronal damage. Previously created chronic, progressive a mouse model of PD by intranasal instillation of a LPS displayed several key features of early-stage PD: a progressive hypokinesia, selective loss of dopamine neurons, a reduction in striatal dopamine content, and α-synuclein (α-syn) accumulation and aggregation in the substance nigra. Other PD model based on nasal inoculation with α-syn aggregates also expressed parkinsonian-like behavioral and immunological features.We suggested that intranasal administration of LPS might cause an increase in expression and misfolding of a-syn in olfactory receptor cells that are projected into olfactory bulbs. We observed an increase in the expression of the native and phosphorylated forms of immunoreactive a-syn in olfactory cells, olfactory nerve and olfactory bulbs where, in addition, activated glial cells were observed. The findings suggest that bacterial antigens can cause parkinsonian-like features both by inducing a glial neuroinflammatory response and by increasing the production of phosphorylated a-syn in peripheral structures of the olfactory system.

Keywords

lipopolysaccharide / Parkinson’s disease / α-synuclein / olfactory neurons

RIGHTS & PERMISSIONS

Sergeyeva T.N., Sergeyeva K.S.