Long-term effect of uncomplicated Plasmodium berghei ANKA malaria on memory and anxiety-like behaviour in C57BL/6 mice

Abstract

BackgroundCerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria.MethodsPlasmodium berghei ANKA-infected and non-infected C57BL/6 mice were used. Development of cerebral malaria was prevented by chloroquine treatment starting on the fourth day of infection. The control group (non-infected mice) were treated with PBS. The effect of uncomplicated malaria infection on locomotor habituation, short and long-term memory and anxious-like behaviour was evaluated 64 days after parasite clearance in assays including open field, object recognition, Y-maze and light/dark tasks.ResultsPlasmodium berghei ANKA-infected mice showed significant long-lasting disturbances reflected by a long-term memory-related behaviour on open field and object recognition tasks, accompanied by an anxious-like phenotype availed on open field and light-dark tasks.ConclusionsLong-term neurocognitive sequels may follow an uncomplicated malaria episode in an experimental model prone to develop cerebral malaria, even if the infection is treated before the appearance of clinical signs of cerebral impairment.

MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25‐35‐induced anxiety and cognitive deficits in a mouse model

“…The Y‐maze apparatus consisted of 3 identical symmetric arms (46 × 3 × 17 cm) with white acrylic walls. The Y‐maze task was conducted as described . Each mouse was placed in the central space and allowed to explore freely for 8 minutes, while their rates of spontaneous alternations were assessed as an indicator of short‐term memory.…”

“…Aβ [25][26][27][28][29][30][31][32][33][34][35] peptides were purchased from Sigma (SI-A4559, Saint Louis, MO 63103, USA), solubilized in sterile distilled water (3 mg/mL), and stored at −20°C until use. For in vitro use, Aβ [25][26][27][28][29][30][31][32][33][34][35] peptides were diluted to 50 μmol/L with physiological saline and aggregated by incubation at 37°C for 4 days before use, as previously described. 21 For in vivo use, Aβ [25][26][27][28][29][30][31][32][33][34][35] peptides were diluted to 10 nmol/L with physiological saline and aggregated by incubation at 37°C for 7 days before bilateral injection into the hippocampal CA1 subregion (i.c.…”

“…The Y-maze task was conducted as described. 26 Each mouse was placed in the central space and allowed to explore freely for 8 minutes, while their rates of spontaneous alternations were assessed as an indicator of short-term memory. Arm entry was defined as the entry of all four paws into one arm.…”

“…To investigate whether MGCD0103 attenuated the anxiety and cognitive deficits induced by oligomeric Aβ [25][26][27][28][29][30][31][32][33][34][35] , we performed OFT, EPM, Y-maze, and MWM experiments. The total distance travelled in the OFT was not different between the four groups ( Figure 1A), which indicates that mice from all groups had normal motor activity.…”

“…MGCD0103, an isotype-selective HDACi, has been clinically evaluated for the treatment of tumors 18 and has also shown a promising pharmacological profile as an anticancer agent, including reliability, tolerance, and safety. 19,20 Therefore, the potential therapeutic effects and mechanisms of MGCD0103 were characterized in mice received with an acute bilateral intrahippocampal CA1 injection of oligomeric Aβ [25][26][27][28][29][30][31][32][33][34][35] .…”