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Borrelia burgdorferi induces matrix metalloproteinases by neural cultures
G Perides1, L M Tanner-Brown, M A Eskildsen
1Tupper Research Institute, Department of Medicine, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts. gperides@caregroup.harvard.edu
Abstract:
Matrix metalloproteinases (MMPs) are associated with chronic neurologic diseases such as multiple sclerosis and senile dementia. Lyme disease is a multisystemic infection involving the nervous system, skin, joints, and heart. Neurologic manifestations of chronic Lyme disease include encephalopathy and cranial and peripheral neuropathy. Borrelia burgdorferi, the spirochaete causing Lyme disease, has been cultured from the cerebrospinal fluid (CSF), and B. burgdorferi DNA is frequently detected in the CSF of patients with Lyme neuroborreliosis. We used cerebral and cerebellar primary cultures to determine whether B. burgdorferi induces the production of MMPs by primary neural cultures. B. burgdorferi in a dose- and time-dependent manner induced the expression of MMP-9 by primary neural cultures but had no effect on the expression of MMP-2. Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures. This response may play a role in the symptomatology and the pathogenesis of Lyme neuroborreliosis.
Insights
Borrelia burgdorferi, the bacterium causing Lyme disease, significantly increases the production of matrix metalloproteinase-9 (MMP-9) in neural cells. This finding offers insights into the neurological aspects of Lyme disease.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are linked to chronic neurological conditions like multiple sclerosis and dementia.
- Lyme disease, caused by Borrelia burgdorferi, affects multiple systems, including the nervous system, leading to neuroborreliosis.
Purpose of the Study:
- To investigate whether Borrelia burgdorferi stimulates MMP production in primary neural cultures.
- To determine the specific MMPs affected by Borrelia burgdorferi infection in neural cells.
Main Methods:
- Utilized primary cerebral and cerebellar neural cultures.
- Incubated cultures with Borrelia burgdorferi in varying doses and durations.
- Analyzed MMP-2 and MMP-9 expression in response to bacterial presence.
Main Results:
- Borrelia burgdorferi induced MMP-9 expression in a dose- and time-dependent manner.
- No significant effect on MMP-2 expression was observed.
- Human and rat astrocytes also exhibited increased MMP-9 production when exposed to Borrelia burgdorferi.
Conclusions:
- Borrelia burgdorferi significantly upregulates MMP-9 in neural cells and astrocytes.
- This MMP-9 induction may contribute to the pathogenesis and symptoms of Lyme neuroborreliosis.