Microglial modulators reduce respiratory rhythm long-term facilitation in vitro
Por:
Polet Camacho-Hernandez, Neira, Julio Lorea-Hernandez, Jonathan, Pena-Ortega, Fernando
Publicada:
1 jul 2019
Resumen:
Inflammation inhibits the expression of some, but not all forms of
respiratory motor plasticity. For example, systemic application of
lipopolysaccharide (LPS) inhibits the phrenic long-term facilitation
induced by moderate intermittent hypoxia in vivo. There are multiple
pro-inflammatory processes triggered by the systemic application of LPS,
including neuroinflammation in the CNS. Considering that microglia can
be activated by the systemic application of LPS, it is likely that this
cell type influences the response of the respiratory circuits to
intermittent hypoxia (IH). Thus, we aimed to test whether modulators of
microglial function would affect the response to IH of the preBotzinger
complex (preBotC) isolated in a brainstem slice preparation. This
experimental approach avoids the systemic influences of these microglial
modulators and limits their effects on cells, mostly microglia, included
in the slice. First, we found that IH (3 x 5-min episodes of bubbling
with 95% N-2 and 5% CO2, mixed with 5-min normoxic intervals by
bubbling with 95% O-2 and 5% CO2) induces a long-lasting increase in
the respiratory rhythm frequency recorded directly from the preBotC,
called in vitro long-term facilitation (LTF), which occurs
simultaneously with a long-lasting decrease in burst amplitude.
Moreover, we found that bath applications of ``microglial activators''
(LPS and fractalkine), ``microglial inhibitors'' (minocycline and
fucoidan) and a microgliotoxin (liposomal clodronate) partially reduce
in vitro LTF. These findings reveal a complex scenario in which both the
activation and the inhibition of microglia halts IH-induced preBotC
plasticity and suggest that experimental or pathological conditions that
affect this cell type, almost in any way, could affect breathing and its
plastic responses.
Filiaciones:
Polet Camacho-Hernandez, Neira:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Blvd Juriquilla 3001, Queretaro 76230, Qro, Mexico
Julio Lorea-Hernandez, Jonathan:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Blvd Juriquilla 3001, Queretaro 76230, Qro, Mexico
Pena-Ortega, Fernando:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Blvd Juriquilla 3001, Queretaro 76230, Qro, Mexico
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