Inhibition of Na+,K+-ATPase from rat brain cortex by propionic acid

Abstract

Buffered propionic acid was injected s.c. into rats twice a day at 8 h intervals from the 6 to 21 days of age. Control rats received saline in the same volumes. The animals were weighed and killed by decapitation at 23 days. Whole brain and cerebral cortex were weighed and synaptic plasma membranes were prepared from cortex for the determination of Na+,K+-ATPase and Mg2+-ATPase activities. Body, whole brain and cortical weights were similar in the two groups, suggesting that propionic acid does not cause malnutrition in rats. Na+,K+-ATPase activity was significantly reduced by 30% in membranes from the propionate-treated group, whereas Mg2+-ATPase activity was not. In another set of experiments, synaptic plasma membranes were prepared from cerebral cortex of 23-day-old rats and incubated with propionic acid at final concentrations ranging from 0.1 to 2.0 mM. Na+,K+-ATPase activity, but not Mg2+-ATPase activity, was inhibited by 22-32%. Since propionic acid concentrations in plasma of chronically treated rats and of propionic acidemic children are of the same order of magnitude as those tested in vitro, the results suggest that the inhibition of Na+,K+-ATPase activity may be related to the neurological dysfunction of patients affected by propionic acidaemia.

Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice

“…Inorganic phosphate production was evaluated by measuring absorbance at 660 nm using malachite green-molybdate dye. The activity was expressed as μM phosphonium ion (Pi) per mg protein per hour [23,24]. Protein concentrations were determined by Coomassie blue staining [25] using bovine serum albumin as a standard.…”

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

“…PPA possesses many neuropharmacological properties which can account for the short-latency behavioral effects observed in this study. PPA inhibits Na + /K + ATPase [78] and increases NMDA receptor sensitivity [47] which can enhance neural depolarization. This organic acid increases glutamatergic transmission leading to neural hyperexcitability in brain regions linked to locomotor activity.…”

Experimental Evidence that Methylmalonic Acid Provokes Oxidative Damage and Compromises Antioxidant Defenses in Nerve Terminal and Striatum of Young Rats

“…Neurotoxic effects of PA have been also reported but to a lesser extent (Wyse et al 1998;Brusque et al 1999;de Mattos-Dutra et al 2000;Fontella et al 2000;Trindade et al 2002;Rigo et al 2006, Ribas et al 2010a. Thus, it has been observed that PA induces lipid peroxidation and decreases non-enzymatic antioxidant defenses in vitro (Fontella et al 2000) and reduces tissue antioxidant defenses in the hippocampus in vivo .…”