Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2

Abstract

Background Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter. Methods Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. Results Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test. Conclusions These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.

Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose‐fed rats

“…Reactive astrocytes observed in hypothalamus of fructose‐fed rats may therefore be recoverable, because betaine treatment suppressed hypothalamic astrocyte activation and reduced proinflammatory markers, being consistent with its protection of fructose‐induced hypothalamic neural injury. These results were supported by other reports that betaine inhibits LPS‐induced neuroinflammation in mice .…”

“…The hepatoprotective effect of betaine has been reported in mice and rats fed with either high‐fat diet or high‐sucrose diet , and in patients with nonalcoholic steatohepatitis . It is interesting that betaine can suppress neuroglial activation to prevent against LPS‐induced neuroinflammation in mice . We recently reported that betaine improved fructose‐caused metabolic abnormality, renal inflammation, and lipid accumulation in rats .…”

Effect of glatiramer acetate on short‐term memory impairment induced by lipopolysaccharide in male mice

“…injection of LPS (250 lg/kg) induces neuronal damage and activation of microglia and astrocytes in the hippocampus. Consistent with our study, Miwa et al [32] employed LPS (250 lg/kg. i.p.)…”

Spermine reverses lipopolysaccharide-induced memory deficit in mice

“…In line with this view, it has been shown that LPS administration impairs contextual fear conditioning [ 8 - 10 ] and spatial memory [ 2 , 11 - 14 ] and avoidance learning [ 15 - 19 ] in rats and mice. In addition, LPS decreases the preference for a novel object in a novel object recognition test in mice [ 20 ]. The comprehension of the mechanisms by which such a deficit occurs may unveil additional (or ratify already-known) regulatory mechanisms of memory consolidation and retrieval in this pathologic condition, thereby guiding the search for novel therapeutic strategies or compounds to mitigate these deficits.…”