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Query: UMLS:C0153640 (
Cerebellum
)
1,777
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cytokine
interleukin-6
(
IL-6
) is produced by cells of the central nervous system (CNS) during a variety of neuroinflammatory states, in which it is thought to play a role in neuroprotection and/or neuropathology associated with neurological disease. In addition, CNS expression of
IL-6
during non-pathological conditions may also occur, although the conditions for such
IL-6
production remain elusive. Expression of
IL-6
and its receptor and signal transducing elements by neurons and glia within the cerebellum implicate a role of
IL-6
in modulating cerebellar function under normal conditions and in contributing to pathology and pathophysiology within the cerebellum during CNS disease states. Evidence for such a role of
IL-6
comes from studies using transgenic mice that chronically express
IL-6
within the CNS. These mice exhibit profound cerebellar pathology and significant alterations of Purkinje neuron electrical and synaptic activity. Additional evidence comes from in vitro studies using primary cultures of cerebellar cortex that have been chronically exposed to exogenously applied
IL-6
. Consistent with the
IL-6
transgenic mice, chronic
IL-6
treated Purkinje neurons in culture exhibit alterations of endogenous electrophysiological properties as well as changes in intracellular Ca2+ homeostasis and signaling. Despite these changes in Purkinje neuron physiology, chronic
IL-6
does not affect the survival or morphology of Purkinje neurons in culture. Thus, by itself,
IL-6
is able to modulate key components of cerebellar circuitry during periods of chronic expression, such as during neuroinflammation, and may be an important player in the movement disorders associated with a number of CNS disease states.
Cerebellum
2005
PMID:Purkinje neuron physiology is altered by the inflammatory factor interleukin-6. 1614 52
Recent studies have established the existence of an innate immune system in the central nervous system (CNS) and implicated a critical role for this system in both normal and pathological processes. Astrocytes and microglia, normal components of the CNS, are the primary cell types that comprise the innate immune system of the CNS. Basic to their role during normal and adverse conditions is the production of neuroimmune factors such as cytokines and chemokines, which are signaling molecules that initiate or coordinate downstream cellular actions. During adverse conditions, cytokines and chemokines function in defensive and repair. However, if expression of these factors becomes dysregulated, abnormal CNS function can result. Both neurons and glial cells of the CNS express receptors for cytokines and chemokines, but the biological consequence of receptor activation has yet to be fully resolved. Our studies show that neuroadaptive changes are produced in primary cultures of rat cerebellar cells chronically treated with the cytokine
interleukin-6
(
IL-6
) and in the cerebellum of transgenic mice that chronically express elevated levels of
IL-6
in the CNS. In the cerebellum in culture and in vivo, the neuroadaptive changes included alterations in the level of expression of proteins involved in gene expression, signal transduction, and synaptic transmission. Associated with these changes were alterations in neuronal function. A comparison of results from the cultured cerebellar cells and cerebellum of the transgenic mice indicated that the effects of
IL-6
can vary across neuronal types. However, alterations in mechanisms involved in Ca(2+) homeostasis were observed in all cell types studied. These results indicate that modifications in cerebellar function are likely to occur in disorders associated with elevated levels of
IL-6
in the cerebellum.
Cerebellum
2013 Jun
PMID:Neuroimmune regulation of neurophysiology in the cerebellum. 2331 8