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HERO ID
4733654
Reference Type
Journal Article
Title
Ammonia role in glial dysfunction in methylmalonic acidemia
Author(s)
Gabbi, P; Nogueira, V; Haupental, F; Rodrigues, FS; Do Nascimento, PS; Barbosa, S; Arend, J; Furian, AF; Oliveira, MS; Dos Santos, ARS; Royes, LFF; Fighera, MR
Year
2018
Is Peer Reviewed?
1
Journal
Toxicology Letters
ISSN:
0378-4274
EISSN:
1879-3169
Volume
295
Page Numbers
237-248
Language
English
PMID
30008432
DOI
10.1016/j.toxlet.2018.06.1070
Abstract
Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution to methylmalonate (MMA)-induced neurotoxicity is poorly understood. The aim of this study was evaluate whether an acute metabolic damage to brain during the neonatal period may disrupt cerebral development, leading to neurodevelopmental disorders, as memory deficit. Mice received a single intracerebroventricular dose of MMA and/or NH4Cl, administered 12 hs after birth. The maze tests showed that MMA and NH4Cl injected animals (21 and 40 days old) exhibited deficit in the working memory test, but not in the reference memory test. Furthermore, MMA and NH4Cl increased the levels of 2',7'-dichlorofluorescein-diacetate (DCF), TNF-α, IL-1β in the cortex, hippocampus and striatum of mice. MMA and NH4Cl also increased glial proliferation in all structures. Since the treatment of MMA and ammonia increased cytokines levels, we suggested that it might be a consequence of the glial activation induced by the acid and ammonia, leading to delay in the developing brain and contributing to behavioral alterations. However, this hypothesis is speculative in nature and more studies are needed to clarify this possibility.
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Malonates
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