Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice.

The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specific combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our findings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the effects of ageing.

Neonatal handling impairs intradimensional shift and alters plasticity markers in the medial prefrontal cortex of adult rats.

Stress response can be modulated by neonatal/childhood events. Neonatal handling (NH) is an animal model in which the animals are subjected to brief separations from the dam during the first days of life, and it leads to lower emotionality and behavioral changes in adulthood. The aim of this study was to observe if early events, such as (NH), may program associative learning and behavioral flexibility in adult male rats and if these changes could be related to altered neurochemistry in the medial prefrontal cortex (mPFC). We evaluated proteins related to synaptic plasticity (brain-derived neurotrophic factor [BDNF] and synaptophysin [SYP]) as well as Na+/K+-ATPase activity. Additionally, we evaluated proteins related to the dopaminergic system (tyrosine hydroxylase [TH] and phosphorylated TH [pTH]), since this system appears to be affected in some neonatal interventions. Neonatally handled animals exhibited impairment in simple discrimination and intradimensional shift but not in reversal or compound discrimination; in addition, no alteration in switching from an egocentric spatial to a cued strategy was observed. These effects were accompanied by a decrease in SYP levels and Na+/K+-ATPase activity, suggesting reduced synaptic function. These results indicate that NH increases attention to irrelevant stimuli and/or impairs associative learning, and this is accompanied by neurochemical alterations in the (mPFC).

Hypericum polyanthemum cyclohexane extract potentiates behavioral effects and neurodegeneration induced by nigral infusions of 6-hydroxydopamine in rats.

INTRODUCTION: Parkinson's Disease (PD) is a progressive neurodegenerative disorder, hallmark of which is loss of nigral dopaminergic neurons. Since a Hypericum polyanthemum extract inhibits monoamine reuptake and some of its constituents present cytotoxic properties, the aim of this study was to evaluate the effect of this extract in an animal PD model. METHODS: Adult Wistar rats (110 days old) received 6-hydroxydopamine (6-OHDA) infusions into the right medial forebrain bundle. A cyclohexane extract from aerial parts of H. polyanthemum (POL; 90 mg/kg/administration; gavage) was administered in three different regimens. In Regimens 1 and 2, rats received 3 administrations of POL starting 4 or 24 h after 6-OHDA infusion, respectively. In Regimen 3, these administrations were carried out 1 day before any evaluation of ipsilateral rotational activity induced by methylphenidate (MP, 20 mg/kg, i.p.). MP was administered 10, 45, and 85 days after 6-OHDA infusion in all groups. Nigral tyrosine hydroxylase (TH) immunocontent was evaluated 120 days after 6-OHDA infusion in animals submitted to Regimen 2 only. The effect of POL on apomorphine-induced climbing behavior in non-lesioned adult CF1 mice (60 days old) treated with POL was also evaluated. RESULTS: Regimen 2 increased MP-induced rotational activity and decreased nigral TH levels in 6-OHDA-lesioned rats. Rotational activity was not altered in regimens 1 and 3. In addition, no change in climbing behavior was observed in non-lesioned mice. CONCLUSION: Together, these results indicate that, in 6-OHDA-lesioned rats, a cyclohexane H. polyanthemum extract potentiates neurotoxicity and MP-induced motor asymmetry depending on the time of administration. In the short term, it seems to not act directly on mice dopaminergic receptors.

Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.

Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.

Proprioceptive deficits in Parkinson's disease: from clinical data to animal experimentation

Parkinson's disease (PD) is characterized by the manifestation of akinesia, slowness to initiate movement, muscle rigidity, and tremors. However, recent evidence indicates that this pathology also causes alterations in proprioception. Disturbances in proprioceptive mechanisms directly affect postural control and the ability to calculate the velocity and amplitude of movement, suggesting that these alterations are related to the motor symptoms of PD. This article reviews the clinical data on these symptoms and presents evidence of a connection between proprioceptive deficits and the physiology of PD. The identification of proprioceptive impairments in different forms of Parkinsonism can provide valuable clues on the physiopathology of proprioception in idiopathic PD.