Thiamine deficiency degrades the link between spatial behavior and hippocampal synapsin I and phosphorylated synapsin I protein levels.

The links between spatial behavior and hippocampal levels of synapsin I and phosphosynapsin I were assessed in normal rats and in the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke-Korsakoff's syndrome. Synapsin I tethers small synaptic vesicles to the actin cytoskeleton in a phosphorylation-dependent manner, is involved in neurotransmitter release and has been implicated in hippocampal-dependent learning. Positive correlations between spontaneous alternation behavior and hippocampal levels of both synapsin I and phosphorylated synapsin I were found in control rats. However, spontaneous alternation performance was impaired in PTD rats and was accompanied by a significant reduction (30%) in phosphorylated synapsin I. Furthermore, no correlations were observed between either form of synapsin I and behavior in PTD rats. These data suggest that successful spontaneous alternation performance is related to high levels of hippocampal synapsin I and phosphorylated synapsin I. These results not only support the previous findings that implicate impaired hippocampal neurotransmission in the spatial learning and memory deficits associated with thiamine deficiency, but also suggest a presynaptic mechanism.

Correlation between phosphorylation level of a hippocampal 86kDa protein and extinction of a behaviour in a model of Wernicke-Korsakoff syndrome.

The effects of chronic ethanol and thiamine deficiency, alone or associated, on hippocampal protein phosphorylation profiles ranging in molecular weight from 30 to 250kDa molecular weight, in stimulated (high K(+) concentration) and unstimulated (basal) conditions were investigated. These treatments significantly changed the phosphorylation level of an 86kDa phosphoprotein. Thiamine deficiency, but not chronic ethanol, induced a decrease in a behavioural extinction index, which is significantly correlated to the phosphorylation level of the p86 protein. These data add to and extend previous findings by our laboratory implicating the involvement of hippocampal neurotransmission components in extinction of a behaviour which involves learning of environmental spatial cues.

Cholinergic parameters and the retrieval of learned and re-learned spatial information: a study using a model of Wernicke-Korsakoff Syndrome.

This is a factorial (2 x 2 x 2) spatial memory and cholinergic parameters study in which the factors are chronic ethanol, thiamine deficiency and naivety in Morris water maze task. Both learning and retention of the spatial version of the water maze were assessed. To assess retrograde retention of spatial information, half of the rats were pre-trained on the maze before the treatment manipulations of pyrithiamine (PT)-induced thiamine deficiency and post-tested after treatment (pre-trained group). The other half of the animals was only trained after treatment to assess anterograde amnesia (post-trained group). Thiamine deficiency, associated to chronic ethanol treatment, had a significant deleterious effect on spatial memory performance of post-trained animals. The biochemical data revealed that chronic ethanol treatment reduced acetylcholinesterase (AChE) activity in the hippocampus while leaving the neocortex unchanged, whereas thiamine deficiency reduced both cortical and hippocampal AChE activity. Regarding basal and stimulated cortical acetylcholine (ACh) release, both chronic ethanol and thiamine deficiency treatments had significant main effects. Significant correlations were found between both cortical and hippocampal AChE activity and behaviour parameters for pre-trained but not for post-trained animals. Also for ACh release, the correlation found was significant only for pre-trained animals. These biochemical parameters were decreased by thiamine deficiency and chronic ethanol treatment, both in pre-trained and post-trained animals. But the correlation with the behavioural parameters was observed only for pre-trained animals, that is, those that were retrained and assessed for retrograde retention.