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Distinct soluble astrocytic factors induce expression of outward K+ currents and ramification of brain macrophages
1Abt. Neurophysiologie, Institut für Physiologie der Charité, HumboldtUniversität zu Berlin, Germany. eder@comcom.rz.charite.hu-berlin.de
Abstract:
Isolated cultured murine brain macrophages (BM) were treated with supernatants of enriched astrocytic cultures. The astrocyte-conditioned medium (ACM) induced ramification of BM. In parallel, BM expressed voltage-gated outward K+ currents (I(K)) during the first 2 days after the application of ACM. However, in ramified BM which were treated once with ACM, I(K) disappeared 5 days after that treatment. In contrast, BM expressed I(K) over a period of more than 5 days when cells were treated daily with ACM. A blockade of I(K) by charybdotoxin or by kaliotoxin did not inhibit ramification of the cells. Furthermore, after application of low-concentrated ACM BM exhibited I(K) but did not change their morphology. It is suggested that in murine BM the ramification and the expression of I(K) are induced by distinct soluble factors derived from astrocytes.
Insights
Astrocyte-conditioned medium (ACM) triggers brain macrophage (BM) ramification and alters potassium currents (I(K)). These effects are mediated by distinct factors, with I(K) expression dependent on the frequency of ACM exposure.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Astrocytes, a type of glial cell in the brain, play crucial roles in neuronal support and immune responses.
- Brain macrophages (BM), the resident immune cells of the central nervous system, are increasingly recognized for their dynamic functions.
- Understanding the interactions between astrocytes and brain macrophages is vital for comprehending neuroinflammation and brain homeostasis.
Purpose of the Study:
- To investigate the effects of astrocyte-conditioned medium (ACM) on the morphology and electrophysiological properties of murine brain macrophages (BM).
- To determine whether the observed changes in BM are induced by distinct soluble factors from astrocytes.
- To elucidate the relationship between astrocyte-derived factors, BM ramification, and the expression of voltage-gated outward K+ currents (I(K)).
Main Methods:
- Primary murine brain macrophages (BM) were cultured and treated with astrocyte-conditioned medium (ACM).
- Morphological changes (ramification) and electrophysiological properties (voltage-gated outward K+ currents, I(K)) of BM were assessed.
- Pharmacological agents (charybdotoxin, kaliotoxin) were used to block I(K) to assess its role in ramification.
Main Results:
- ACM induced ramification in BM.
- ACM treatment led to the expression of I(K) in BM within 2 days, which disappeared after 5 days following a single treatment.
- Daily ACM treatment sustained I(K) expression for over 5 days, while I(K) blockade did not inhibit ramification.
- Low-concentration ACM induced I(K) without altering BM morphology.
Conclusions:
- Astrocytes release distinct soluble factors that differentially regulate brain macrophage (BM) ramification and voltage-gated outward K+ current (I(K)) expression.
- The expression of I(K) in BM is dependent on the frequency of astrocyte-derived factor exposure.
- These findings suggest a complex paracrine signaling network between astrocytes and brain macrophages influencing immune cell function in the CNS.