Influence of very low doses of baclofen, a GABA-B receptor agonist, on neiroinflammatory protein expression in non-trangenic AD-type model-rats

Šī darba mērķis bija noteikt GABAB receptora agonista baklofēna ļoti mazo devu (0,025 un 0,05 mg/kg) efektus uz neiroiekaisumu (GFAP) un acetilholīna šķelšanu (AChE) streptozocīna (STZ) icv AD-tipa žurku modelī. Rezultāti rāda, ka: a) STZ ievadīšana izraisīja statistiski ticamu GFAP un AChE blīvuma palielinājumu smadzenēs, norādot uz neiroiekaisumu un palielinātu acetilholīna daudzuma samazināšanos b) Abās devās baklofēns aizsargāja pret STZ inducēto neiroiekaisumu, būtiski samazinot GFAP blīvumu līdz kontroles grupas rādītājiem; c) Baklofēna ievadīšana normalizēja arī STZ ievadīšanas rezultātā palielinātu acetilholīna šķelšanu. Iegūti dati liecina, ka GABAB agonista baklofēna ļoti mazās devās spēj protektēt pret neiroiekaisumu un palielināt acetilholīna līmeni ICV STZ Alcheimera slimības modeļa žurku smadzenēs. Šūnas mērķi (targets), kas realizē šos procesus paliek turpmākai noskaidrošanai. Atslēgvārdi: Alcheimera slimība, neiroiekaisums, baklofēns, GFAP, AChEThe aim of the present study was to detect the effects of GABAB receptor agonist baclofen at very low doses (0.025 mg/kg and 0.05 mg/kg) on neuroinflammation (GFAP) and acetylcholine cleavage (AChE) in STZ intracerebroventricular (icv) AD-type model rats. The results show that: a) ICV STZ administration resulted in significantly higher GFAP and AChE density, thereby inducing neuroinflammation and acetylcholine cleavage; b) Baclofen at both doses protected against STZ-induced neuroinflammation by showing GFAP density values similar to that of the control group; c) At both doses, baclofen also normalized levels of acetylcholine to that observed in the control group. The obtained data show that GABAB agonist baclofen at very low doses can protect against astroglial inflammation and increase the amount of acetylcholine in the brains of icv STZ AD model rats. The cellular targets which participate in this regulatory action remain to be elucidated. Keywords: Alzheimer’s disease, neuroinflammation, baclofen, GFAP, ACh