5.1 What is the role of other histamine receptors in
epilepsy?
H1R and H3R expression have been merely detected in one type of epilepsy
animal model. The changes of histamine receptors need systemic animal
researches and autopsy studies to elucidate further, especially H2R and
H4R. In addition, H1R, H2R and H3R antagonists have been investigated in
many epilepsy animal model, however, the report of H4R in epilepsy is
still missing. Even the H4R shows the potential in regulating neuronal
excitability (Desmadryl et al., 2012). Investigations should be
implemented to detect the distribution and expression of H4R in epilepsy
animal, and applying H4R agonists and antagonists to epilepsy
intervention. What’ more, some studies found that action of H3R ligands
relies on H1R or H2R, the specific histamine receptor KO mice are
available to ensure the action of H3R antagonist through H1R or H2R.
Even the H3R antagonists receive a lot of attention upon its desirable
anti-epileptic and anticonvulsant effects, the action manner of H3R
antagonists is not fully understood. As H3R is identified as either
autoreceptor or heteroreceptor, it may be very complex about how it
regulates neural excitability and thus related in epilepsy. For example,
it is still largely unknown whether histamine-independent signaling is
involved in the anti-seizure effect of H3R antagonists/inverse agonists.
In the cerebral ischemia/reperfusion injury, the H3R antagonists protect
against the ischemia injury in a histamine independent manner by
directly recruiting binding of CLIC4 with H3R (Yan et al., 2014).
Whether the action of H3R antagonist is the same in epilepsy that is
unclear. HDC inhibitors and HDC-KO animal are regarded as a good choice
to answer this question.