Free L-glutamate-induced modulation in oxidative and neurochemical profile contributes to enhancement in locomotor and memory performance in male rats

Abstract

Glutamate (Glu), the key excitatory neurotransmitter in the central nervous system, is considered essential for brain functioning and has a vital role in learning and memory formation. Earlier it was considered as a harmful agent but later found to be useful for many body functions. However, studies regarding the effects of free L-Glu administration on CNS function are limited. Therefore, current experiment is aimed to monitor the neurobiological effects of free L-Glu in male rats. L-Glu was orally administered to rats for 5-weeks and changes in behavioral performance were monitored. Thereafter, brain and hippocampus were collected for oxidative and neurochemical analysis. Results showed that chronic supplementation of free L-Glu enhanced locomotor performance and cognitive function of animals which may be attributed to the improved antioxidant status and cholinergic, monoaminergic and glutamatergic neurotransmission in brain and hippocampus. Current results showed that chronic supplementation of L-Glu affects the animal behaviour and brain functioning via improving the neurochemical and redox system of brain. Free L-Glu could be a useful therapeutic agent to combat neurological disturbances however this requires further targeted studies.

Figure 1

Schematic representation of treatment schedule and experimental design.

Figure 2

Effect on locomotor activity was evaluated via monitoring (a) ambulatory performance which is evaluated by open field test in terms of latency (s) to move from the central square (left) the number of squares crossed (right), (b) muscular strength evaluated by Kondziela’s Inverted screen test in terms of latency (s) to fall from the inverted screen and (c) motor coordination evaluated by Beam walking test in terms of latency (s) to cross the beam and number of foot slips off the beam on three different beam sizes (3 cm, 2 cm and 1 cm). For each group n = 6 and values are presented as mean ± S.D. All significant differences are expressed as * P < 0.05, ** P < 0.01 compared to control group.

Figure 3

Effect on memory performance is presented; (1) Recognition memory in terms of (a) sniffing time for familiar (old) and novel object and (b) discrimination index; (2) Spatial memory performance in terms of (c) escape latencies of acquisition training trials, (d) averaged escape latencies, (e) spatial reference memory acquisition (1 h probe trial) and (f) retention (24 h probe trial) by monitoring escape latency time, latency to find the target quadrant (NW), duration of time spent (seconds) in the target quadrant and the number of entries made by rat over target quadrant; (3) Associative memory performance in terms of (g) step-trough latency difference. For each group n = 6 and values are presented as mean ± S.D. Significant differences were expressed as ** P < 0.01 compared to control group and for training trials ** P < 0.01 compared to control and ++ P < 0.01 compared to trial 1.

Figure 4

Effect on oxidative profile of rats was assessed via determining the levels of major oxidant (MDA) (a), levels of antioxidant (GSH and Protein) compounds (b) and levels of antioxidant enzymes (CAT, GPx, SOD) (c). For each group n = 6 and values are presented as mean ± S.D. Significant differences were expressed as ** P < 0.01 compared to control group.

Figure 5

Effect on cholinergic and glutamatergic profile of rats was assessed via determining the levels of ACh content (a) and AChE activity (b) and the levels of hippocampal Glu (c) and GABA (d). For each group n = 6 and values are presented as mean ± S.D. Significant differences were expressed as ** P < 0.01 compared to control group.

Figure 6

Effect on brain and hippocampal monoaminergic profile of rats was assessed via determining the levels of monoamines [NA (a), DA (b), 5-HT (c)] and its metabolites [DOPAC (b), HVA (b), 5-HIAA (c)] and ratio HVA/DA ratio (d) and 5HIAA/5HT (e). For each group n = 6 and values are presented as mean ± S.D. Significant differences were expressed as ** P < 0.01 compared to control group.

Figure 7

Schematic representation of findings following chronic supplementation of free Glu in rats.