Involvement of histamine 1 receptor in seizure susceptibility and neuroprotection in immature mice.
The central histaminergic neuronal system is a powerful modulator of brain activity, and its functional disturbance is related to e.g. epilepsy. We have recently shown in the slice culture system that histaminergic neurons attenuate kainic acid (KA)-induced epileptiform activity and neuronal damage in the hippocampus through histamine 1 (H1) receptors. We now further examined the role of H1 receptors in the regulation of KA-induced seizures and neuronal damage in immature 9-day-old H1 receptor knock out (KO) mice. In the H1 receptor KO mice, behavioral seizures were significantly more severe and duration of seizures was significantly longer when compared to the wild type (WT) mice at the KA dose of 2mg/kg. Moreover, neuronal damage correlated with seizure severity, and it was significantly increased in the thalamus and retrosplenial granular cortex (RGC) of the KO mice. The H1 receptor antagonist triprolidine treatment supported these findings by showing significantly increased seizures severity and neuronal damage in the septum, thalamus, CA3 region of the hippocampus, and RGC in the KA-treated WT mice. Our present novel findings suggest that H1 receptors play a pivotal role in the regulation of seizure intensity and duration as well as seizure-induced neuronal damage in the immature P9 mice.
Kukko-Lukjanov
Tiina-Kaisa
TK
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itainen Pitkakatu 4B, 20520 Turku, Finland. tiikuk@utu.fi
Lintunen
Minnamaija
M
Jalava
Niina
N
Laurén
Hanna B
HB
Lopez-Picon
Francisco R
FR
Michelsen
Kimmo A
KA
Panula
Pertti
P
Holopainen
Irma E
IE
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D007608:Kainic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009930:Organic Chemicals; D011969:Receptors, Histamine H1 / Q000172:deficiency / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014311:Triprolidine / Q000627:therapeutic use*
D005452:Fluoresceins; D006634:Histamine H1 Antagonists; D009930:Organic Chemicals; D011969:Receptors, Histamine H1; C435731:fluoro jade; D014311:Triprolidine; D007608:Kainic Acid