4.3 The genetic and other therapeutics effects of
targeting histamine and histamine receptors on epilepsy in animal
model
Since histamine and its precursor L-histidine, as well as most H3R
antagonists obtain positive outcomes. As pharmacological modulation is
often associated with non-specific effect, genetically intervention can
address the precise role of central histaminergic signaling epilepsy
more specifically.
The H1R-KO mice showed more severe seizures with correlation of neuronal
damage in the thalamus and RGC in P9 immature mice (Kukko-Lukjanov et
al., 2010). Those authors then described the age-dependent
susceptibility of H1R-KO mice to seizure-induced by KA administration:
P14 H1R-KO mice showed no changes; P21 KO mice decreased survival rate
with more severe seizures and enhanced neuronal damage in various brain
regions; P60 KO mice increased the neuronal damage without changing the
seizure severity (Kukko-Lukjanov et al., 2012). In the HDC-KO mice, the
hyperthermia-induced febrile seizure was more severe that wide type (WT)
mice (Dai et al., 2015). These findings indicate that deletion of H1R
and HDC increases the susceptibility of epilepsy.
Based on the above researches results, it can be basically concluded
that the central histaminergic signaling participates in epilepsy. Most
importantly, the H3R antagonist shows powerful anti-epileptic and
anticonvulsant effects in many epileptic animal models. The protective
effect of H3R antagonist works mainly through H1R. However controversial
opinion still exists (Alachkar et al., 2019; Sadek, Saad, Subramanian,
Shafiullah, Łażewska & Kieć-Kononowiczc, 2016). What’s more, the action
of H1R antagonists in seizure animal model also not consistent. The
incomplete understanding of these issues needs further studies to
investigate.