Naslov
Neuroprotective effect of AChE reactivator RS194B on neuronal and glial cells of mice exposed to nerve agent
(Neuroprotective effect of AChE reactivator RS194B on neuronal and glial cells of mice exposed to nerve agent)

Autori
Maček Hrvat, Nikolina ; Ilić, Katarina ; Kolić, Dora ; Taylor, Palmer ; Kalanj Bognar, Svjetlana ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
17th International Symposium on Cholinergic Mechanisms (ISCM2022): Programme and Abstracts / Kovarik, Zrinka ; Primožič, Ines - Zagreb : Institut za medicinska istraživanja i medicinu rada, 2022, 26-26

ISBN
978-953-96817-8-2

Skup
17th International Symposium on Cholinergic Mechanisms (ISCM2022)

Mjesto i datum
Mlini, Hrvatska ; Dubrovnik, Hrvatska, 08.05.2022. - 12.05.2022

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
neuroprotection ; organophosphate ; neuroinflamation ; oxime ; GFAP ; IBA-1 ; NeuN

Sažetak
Acutely toxic, small lipophilic organophosphate (OP) molecules readily cross the blood-brain barrier and inhibit the physiological function of acetylcholinesterase (AChE) - hydrolysis of the neurotransmitter acetylcholine. Consequently, hypercholinergic activity will induce seizures which lead to brain damage and trigger neuroinflammation. Also, overstimulation of nicotinic and muscarinic membrane receptors will induce symptoms of cholinergic crises, which in severe cases can lead to hypoxia, vasodepression, and respiratory arrest, followed by death. Therapy against OP poisoning includes oxime compounds that can restore AChE activity preventing the cholinergic crisis and an anti-muscarinic drug, such as atropine. Nevertheless, oximes currently approved for therapy do not cross the blood-brain barrier readily, due to the permanent positive charge, and cannot restore the activity of synaptic AChE, leaving the brain vulnerable to long-term damage. We anticipate that the treatment with uncharged, but ionizable oximes that cross the blood-brain barrier and reactivate OP- inhibited synaptic AChE will act protectively on the brain of mice exposed to a nerve agent. For that purpose, we have investigated the effect of centrally acting oxime RS194B in the brain of mice exposed to a nerve agent and compared it to poisoned mice by monitoring effects on neuronal and glial cells. A microglial response, detected with IBA-1 protein, glial cells, detected with glial fibrillary acidic protein (GFAP), and neuronal cell viability, detected by the neuronal nuclei antigen NeuN were all monitored to track the level of GFAP and IBA-1 proteins, and the preservation of NeuN expression in order to indicate the survival of neurons and neuroprotection by uncharged, ionizable oxime in mice exposed to a nerve agent. This research was supported by the HDTRA-19- 1-006-UCSD-113020, and Croatian Science Foundation (IP-2018-01-7683, and IP- 2016-06-8636).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA