Objective: Early stress events severely impact brain and behaviour. From a neurobiological point of view early stress influences neuroanatomical structures and is associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The objective of this article is to review the epigenetic alterations implicated in brain adaptation to early stress events.

Method: A review of empirical research of epigenetic alterations associated to early stress events was performed.

Results: Neuroanatomic and epigenetic alterations have been observed after early stress events. Epigenetics alterations include DNA methylation, histones modifications and microRNA (miRNA) expression. The most studied is largely the former, affecting genes involved in neuroendocrine, neurotransmission and neuroplasticity regulation after early stress exposition. It includes glucocorticoid receptor, FK506-binding protein 5, arginine vasopressin, oestrogen receptor alpha, 5-hydroxy-tryptamine transporter and brain-derived neurotrophic factor.

Conclusion: Epigenetic regulation is critical in the interplay between nature and nurture. Alterations in the DNA methylation as well as histones modifications and miRNA expression patterns could explain abnormal behaviours secondary to early stress events.

Objective: Mental fatigue occurring after a stroke or traumatic brain injury (TBI) often results in difficulties returning to work and pursuing social activities. No effective treatment of this condition is available today. In this study, we have tested a novel pharmacological strategy using the monoaminergic stabiliser (−)-OSU6162.

Methods: (−)-OSU6162 was given orally for 4 weeks in doses increasing from 15 to 45 mg b.i.d. to 12 patients suffering from mental fatigue, following upon stroke (n=6) or TBI (n=6). (−)-OSU6162 was compared with placebo using a double-blind, randomised cross-over design. Patients included were well rehabilitated physically with no gross impairment in cognitive functions other than those related to the mental fatigue.

Results: (−)-OSU6162 caused a remarkable improvement in mental stamina, as evaluated by a self-assessment scale on mental fatigue. Statistical significance was reached on the primary endpoint (Mental Fatigue Scale). There was a trend towards improvement in the secondary endpoints processing speed and attention. Principal component analysis showed an overall positive treatment effect in 7 of 12 patients. Beneficial responses were seen already during the first few days of active drug treatment. Increasing dosage caused no further improvement. Adverse reactions consisted of short-lasting mild nausea and attenuated appetite. These side effects disappeared upon dose reduction.

Conclusion: The monoaminergic stabiliser (−)-OSU6162 offers promise as a candidate for treatment of mental fatigue after a stroke or TBI.

Réus GZ, Stringari RB, Rezin GT, Pezente DP, Scaini G, Maggi DD, De-Nês BT, Streck EL, Quevedo J, Feier G. Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain.

Objective: Electroconvulsive therapy is used efficacious treatment for a variety of complicated psychiatric disorders and evidences have indicated that energy metabolism impairment may be involved in pathophysiology and treatment of mood disorders. This work was performed to determine creatine kinase and mitochondrial respiratory chain activities at different times after the maintenance electroconvulsive shock (ECS).

Methods: Male Wistar rats received a protocol mimicking therapeutic of maintenance or simulated ECS (sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance ECS. We measured creatine kinase and mitochondrial respiratory chain activities in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum.

Results: Our results showed that maintenance ECS alter respiratory chain complexes and creatine kinase activities in the rat brain, but these effects were related to brain area and time after the ECS, in which the animal were killed.

Conclusion: Finally, these findings further support the hypothesis that alteration on the energy metabolism could be involved in the therapeutic or adverse effects of ECS.

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation.

Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography.

Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions.

Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.

Krass M, Rünkorg K, Vasar E, Volke V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice.

Objective: The aim of this study was to compare the behavioural and hormonal effects of systemic (subcutaneous) treatment with glucaemically equipotent doses of exenatide and liraglutide in mice.

Methods: The effects of glucagon-like peptide-1 (GLP-1) receptor agonists were determined on anxiety level in the light–dark compartment test, the motor activity in automated activity cages and finally the forced swimming test was performed.

Results: Both exenatide (1–20 µg/kg) and liraglutide (200–1200 µg/kg) decreased the glucose levels up to 30% in freely fed animals. In glucaemically equipotent doses the drugs induced very similar behavioural and hormonal effects: there was no change on anxiety level or immobility time, however, both drugs suppressed motor activity and increased corticosterone levels.

Conclusion: We conclude that the two clinically approved GLP-1 receptor agonists induce very similar suppression of motor activity and stimulation of corticosterone release in mice.

Barichello T, Generoso JS, Cipriano AL, Casagrande R, Collodel A, Savi GD, Scherer EBS, Kolling J, Wyse ATS. Increase Na+,K+-ATPase activity in the rat brain after meningitis induction by Streptococcus pneumoniae.

Background: Pneumococcal meningitis is the most severe infection of the central nervous system with a mortality rate up to 20% and an adverse neurological result in up to 50% of survivors. A complicated series of interactions among the host immune response and oxidants seems to be responsible for meningitis associated brain dysfunctions. Na+,K+-ATPase is an essential enzyme responsible for generating and maintaining the membrane potential necessary for neural excitability, however, the Na+,K+-ATPase activity is altered in several illness;

Objective: The aim of this study is to evaluate the Na+,K+-ATPase activity in hippocampus and cortex of the rats submitted to pneumococcal meningitis.

Methods: Animals received 10 µl sterile saline as a placebo or an equivalent volume of Streptococcus pneumoniae to the concentration of 5 × 109cfu/ml and were killed at 24, 48, 72 and 96 h after meningitis induction. The brain structures, hippocampus and cortex, were immediately isolated on dry ice and stored at −80°C to analyse Na+,K+-ATPase activity.

Results: In the hippocampus, we verified the increase of Na+,K+-ATPase activity at 48, 72 and 96 h (p < 0.05) and in the cortex at 24 h (p < 0.05) after pneumococcal meningitis induction.

Conclusion: The Na+,K+-ATPase activity is under the control of a diversity of intracellular messengers that are able to modulate the function of the particular isozymes in a precise way. Furthermore, we verified that pneumococcal meningitis increased the Na+,K+-ATPase activity in hippocampus and cortex; this increase can be correlated with a compensatory mechanism in illness pathophysiology.

Background: This is a report of a 66-year-old male with Parkinson's disease (PD), depression and anxiety who developed tardive dyskinesia (TD) while on fluoxetine.

Methods: The patient underwent psychiatric, neurological and neuroimaging examination.

Results: The patient's neuroimaging examination was normal, his psychiatric assessment revealed depression and anxiety, and his neurological evaluation diagnosed only mild PD. The patient's TD resolved when fluoxetine was discontinued and recurred upon re-exposure.

Conclusion: This case shows that fluoxetine as monotherapy can be associated with TD especially in patients with concomitant PD. Clinicians must be aware of this side-effect and monitor for features of TD due to antidepressants that are often used to treat comorbid depression in patients with PD.

Ozdilek B, Uluc K, Gunal DI. Bilateral striopallidodentate calcinosis presenting with psychiatric symptoms and speech disorders.

Background: Bilateral striopallidodentate calcinosis (BSPDC), also known as Fahr's disease, is a rare neurodegenerative disorder characterised by the deposition of calcium and other minerals in the basal ganglia, centrum semiovale and cerebellum. It is usually idiopathic. Its clinical manifestations vary from asymptomatic individuals to neuropsychiatric abnormalities, movement disorders, cerebellar symptoms and cognitive impairments.

Methods: Five cases of BSPDC – all of which include psychiatric symptoms and speech problems – from two families are documented in this article.

Conclusion: The most important diagnostic marker is the demonstration of symmetrical intracranial calcifications. Computerised tomography of the brain is the most frequently used radiologic method to diagnose BSPDC.