Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy.

PURPOSE: Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). METHODS: To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was coadministered with Pilo in a subgroup of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histologic labeling of zinc mossy fiber terminals in the dentate gyrus (DG). KEY FINDINGS: Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, whereas chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to nonepileptic control animals. A strong correlation (r = 0.81, p < 0.001) was found between MEMRI signal enhancement and MFS. SIGNIFICANCE: This study shows that MEMRI is an attractive noninvasive method for detection of mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy.

Infusion of protein synthesis inhibitors in the entorhinal cortex blocks consolidation but not reconsolidation of object recognition memory.

Memory consolidation and reconsolidation require the induction of protein synthesis in some areas of the brain. Here, we show that infusion of the protein synthesis inhibitors anisomycin, emetine and cycloheximide in the entorhinal cortex immediately but not 180 min or 360 min after training in an object recognition learning task hinders long-term memory retention without affecting short-term memory or behavioral performance. Inhibition of protein synthesis in the entorhinal cortex after memory reactivation involving either a combination of familiar and novel objects or two familiar objects does not affect retention. Our data suggest that protein synthesis in the entorhinal cortex is necessary early after training for consolidation of object recognition memory. However, inhibition of protein synthesis in this cortical region after memory retrieval does not seem to affect the stability of the recognition trace.

Intraventricular cycloheximide attenuates the restraint-induced long-lasting effect on plus maze exploration.

Rats submitted to 2 h of restraint stress show reduced open arm exploration in the elevated plus maze 24 h later. To determine if this effect is dependent on protein synthesis during or after the restraint period, cycloheximide, a protein synthesis inhibitor, was injected into the right cerebral ventricle of male Wistar rats (200-250 g), immediately before (N = 19 animals per group), immediately after (N = 7 animals per group) or 2 h (N = 10 animals per group) following a 2-h period of forced restraint. Twenty-four hours later the animals were tested in the elevated plus maze. Non-stressed control groups received saline (SAL, N = 8-9 per group) or cycloheximide (CHX, N = 8-9 per group) and were tested 1 h or 24 h later in the maze. Pre- but not post-stress microinjections of cycloheximide (20 micrograms in 2 microliters) increased exploration in the elevated plus maze (% of time spent in open arms, pre-stress injection: SAL = 4.6 +/- 1.2, CHX = 10.7 +/- 2.3; number of enclosed arms entries: SAL = 3.6 +/- 0.5, CHX = 5.6 +/- 0.4). No drug effect was observed in non-stressed animals. These results suggest that blockade of protein synthesis during the restraint period may attenuate the behavioral consequences of stress.

Intraventricular cycloheximide attenuates the restraint-induced long-lasting effect on plus maze exploration

Rats submitted to 2 h of restraint stress show reduced open arm exploration in the elevated plus maze 24 h later. To determine if this effect is dependent on protein synthesis during or after the restraint period, cycloheximide, a protein synthesis inhibitor, was injected into the right cerebral ventricle of male Wistar rats (200-250 g), immediately before (N = 19 animals per group), immediately after (N = 7 animals per group) or 2 h (N = 10 animals per group) following a 2h period of forced restraint. Twenty-four hours later the animals were tested in the elevated plus maze. Non-stressed control groups received saline (SAL, N = 8-9 per group) or cycloheximide (CHX, N = 8-9 per group) and were tested 1 h or 24 h later in the maze. Pre- but not post-stress microinjections of cycloheximide (20 mug in 2 mul) increased exploration in the elevated plus maze (per cent of time spent in open arms, pre-stress injection: SAL = 4.6 ñ 1.2, CHX = 10.7 2.3; number of enclosed arms entries: SAL = 3.6 ñ 0.5, CHX = 5.6 0.4). No drug effect was observed in non-stressed animals. These results suggest that blockade of protein synthesis during the restraint period may attenuate the behavioral consequences of stress.