Behavioural brain research
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Previous studies in our lab have shown that slight modifications in the spatial reference memory procedure can overcome the deficit in spatial learning typically observed in rats with hippocampal damage. However, it is unknown if memory acquired under such training circumstances is spared after hippocampal lesions. With this aim a four-arm plus-shaped maze and a spatial reference memory paradigm were used, in which the goal arm was doubly marked: by an intramaze cue (a piece of sandpaper positioned on the floor of the arm) and by the extramaze constellation of stimuli around the maze. ⋯ Experiment 2 investigated the effect of hippocampal damage 1 day after the learning. Results showed that regardless of the training procedure employed (with or without the intramaze cue), hippocampal lesions produced a profound retrograde amnesia. Thus, although the absence of anterograde amnesia suggests that structures other that the hippocampus can take charge of the acquisition, the presence of retrograde amnesia indicates the critical role of the normal hippocampus in the long-term formation of allocentric information.
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The present study explored the possibility that cholinergic and GABAergic systems of medial septum (MS) might influence acquisition of memory by regulation of acetylcholine (Ach) and γ-aminobutyric acid (GABA) receptors function in hippocampus and vice versa. The step-through passive avoidance (PA) task was used. The results showed that pre-training intra-MS/CA1 administration of nonselective muscarinic Ach antagonist, scopolamine (0.5, 1 and 2 μg/rat) and GABA(A) receptor agonist, muscimol (0.01 and 0.02 μg/rat) impaired, while acetylcholinesterase inhibitor, physostigmine (0.5 and 1 μg/rat) and GABA(A) receptor antagonist, bicuculline (0.25 μg/rat) improved memory acquisition. ⋯ Also, the result revealed that, intra-CA1/MS administration subthreshold dose of muscimol reduced improvement of memory induced by physostigmine in the MS/CA1, respectively (cross injection). On the other hand, subthreshold dose of bicuculline in CA1/MS did not alter memory improvement induced by physostigmine in the other site (MS/CA1). In conclusion, both cholinergic and GABAergic systems not only seem to play a role in the modulation of memory in the MS and CA1 but also to have a complex interaction.
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While late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), alone and in combination, is associated with an increased risk of incident Alzheimer's disease (AD), the neurobiological mechanisms of this link are unclear. We examined the main and interactive effects of LLD and aMCI on the gray matter (GM) volumes in 72 physically healthy participants aged 60 and older. Participants were separated into normal controls, cognitively normal depressed, non-depressed aMCI, and depressed aMCI groups. ⋯ LLD-aMCI interactions were associated with widespread subcortical and cortical GM volume loss of brain structures implicated in AD. The interactions between episodic memory deficits and depressive symptom severity are associated with volume loss in right inferior frontal gyrus/anterior insula and left medial frontal gyrus clusters. Our findings suggest that the co-existence of these clinical phenotypes is a potential marker for higher risk of AD.
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Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. ⋯ The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD.
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Guanosine is an extracellular signaling molecule implicated in the modulation of glutamatergic transmission and neuroprotection. The present study evaluated the antidepressant-like effect of guanosine in the forced swimming test (FST) and in the tail suspension test (TST) in mice. The contribution of NMDA receptors as well as l-arginine-NO-cGMP and PI3K-mTOR pathways to this effect was also investigated. ⋯ In addition, the administration of ketamine (0.1 mg/kg, i.p., a NMDA receptor antagonist), MK-801 (0.001 mg/kg, i.p., another NMDA receptor antagonist), 7-nitroindazole (50 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of guanosine (0.01 mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. None of the treatments affected locomotor activity. Altogether, results firstly indicate that guanosine exerts an antidepressant-like effect that seems to be mediated through an interaction with NMDA receptors, l-arginine-NO-cGMP and PI3K-mTOR pathways.