Title : Involvement of the Cholinergic Parameters and Glial Cells in Learning Delay Induced by Glutaric Acid: Protection by N-Acetylcysteine - Rodrigues_2019_Mol.Neurobiol_56_4945 |
Author(s) : Rodrigues FS , de Zorzi VN , Funghetto MP , Haupental F , Cardoso AS , Marchesan S , Cardoso AM , Schinger MRC , Machado AK , da Cruz IBM , Duarte M , Xavier LL , Furian AF , Oliveira MS , Santos ARS , Royes LFF , Fighera MR |
Ref : Molecular Neurobiology , 56 :4945 , 2019 |
Abstract :
Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Rat pups were injected with GA (5 mumol g body weight(-1), subcutaneously; twice per day; from the 5th to the 28th day of life) and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). We found that GA injection caused delay procedural learning; increase of cytokine concentration, oxidative markers, and caspase levels; decrease of antioxidant defenses; and alteration of acetylcholinesterase (AChE) activity. Interestingly, we found an increase in glial cell immunoreactivity and decrease in the immunoreactivity of nuclear factor-erythroid 2-related factor 2 (Nrf2), nicotinic acetylcholine receptor subunit alpha 7 (alpha7nAChR), and neuronal nuclei (NeuN) in the striatum. Indeed, NAC administration improved the cognitive performance, ROS production, neuroinflammation, and caspase activation induced by GA. NAC did not prevent neuronal death, however protected against alterations induced by GA on Iba-1 and GFAP immunoreactivities and AChE activity. Then, this study suggests possible therapeutic strategies that could help in GA-I treatment and the importance of the striatum in the learning tasks. |
PubMedSearch : Rodrigues_2019_Mol.Neurobiol_56_4945 |
PubMedID: 30421167 |
Rodrigues FS, de Zorzi VN, Funghetto MP, Haupental F, Cardoso AS, Marchesan S, Cardoso AM, Schinger MRC, Machado AK, da Cruz IBM, Duarte M, Xavier LL, Furian AF, Oliveira MS, Santos ARS, Royes LFF, Fighera MR (2019)
Involvement of the Cholinergic Parameters and Glial Cells in Learning Delay Induced by Glutaric Acid: Protection by N-Acetylcysteine
Molecular Neurobiology
56 :4945
Rodrigues FS, de Zorzi VN, Funghetto MP, Haupental F, Cardoso AS, Marchesan S, Cardoso AM, Schinger MRC, Machado AK, da Cruz IBM, Duarte M, Xavier LL, Furian AF, Oliveira MS, Santos ARS, Royes LFF, Fighera MR (2019)
Molecular Neurobiology
56 :4945