Willie M. U. Daniels

The effect of electromagnetic radiation in the mobile phone range on the behaviour of the rat.

Electromagnetic radiation (EMR) is emitted from electromagnetic fields that surround power lines, household appliances and mobile phones. Research has shown that there are connections between EMR exposure and cancer and also that exposure to EMR may result in structural damage to neurons. In a study by Salford et al. (Environ Health Perspect 111:881–883, 2003) the authors demonstrated the presence of strongly stained areas in the brains of rats that were exposed to mobile phone EMR. These darker neurons were particularly prevalent in the hippocampal area of the brain. The aim of our study was to further investigate the effects of EMR. Since the hippocampus is involved in learning and memory and emotional states, we hypothesised that EMR will have a negative impact on the subject’s mood and ability to learn. We subsequently performed behavioural, histological and biochemical tests on exposed and unexposed male and female rats to determine the effects of EMR on learning and memory, emotional states and corticosterone levels. We found no significant differences in the spatial memory test, and morphological assessment of the brain also yielded non-significant differences between the groups. However, in some exposed animals there were decreased locomotor activity, increased grooming and a tendency of increased basal corticosterone levels. These findings suggested that EMR exposure may lead to abnormal brain functioning.

Brain-derived neurotrophic factor: the neurotrophin hypothesis of psychopathology.

While monoaminergic hypotheses of psychopathology remain popular, there has been growing interest in the role of neurotrophins in neuropsychiatric disorders. Basic laboratory work has documented the importance of neurotrophins in neuronal survival and synaptic plasticity, and a range of clinical studies has provided analogous evidence of their role in neuropathology. Work on gene variants in brain-derived neurotrophic factor, and associated changes in structural and function brain imaging, have further contributed to our understanding of this area. Much remains to be done to delineate fully the relevant mechanisms by which brain-derived neurotrophic factor and other neurotrophins contribute to psychopathology, and to develop targeted therapeutic interventions. Nevertheless, the neurotrophin hypothesis has already given impetus to a range of valuable research.

Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation

Many studies have reported on the detrimental effects of early life adversity and the beneficial effects of exercise on brain function. However, the molecular mechanisms that underpin these various effects remain poorly understood. The advent of advanced proteomic analysis techniques has enabled simultaneous measurement of protein expression in a wide range of biological systems. We therefore used iTRAQ proteomic analysis of protein expression to determine whether exercise counteracts the detrimental effects of early life adversity in the form of maternal separation on protein expression in the brain. Rat pups were subjected to maternal separation from postnatal day 2 to 14 for 3 h day−1 or normally reared. At 40 days of age, half of the rats in each group (maternal separation and normally reared) were allowed to exercise voluntarily (access to a running wheel) for 6 weeks and the remainder kept as sedentary control animals. At 83 days of age, rats were killed and the ventral hippocampus was dissected for quantitative proteomic (iTRAQ) analysis. The iTRAQ proteomic analysis identified several proteins that had been altered by maternal separation, including proteins involved in neuronal structure, metabolism, signalling, anti‐oxidative stress and neurotransmission, and that many of these proteins were restored to normal by subsequent exposure to voluntary exercise in adolescence. Our data show that a broad range of proteins play a role in the complex consequences of adversity and exercise.

Early maternal separation leads to down-regulation of cytokine gene expression.

Exposure to stressors may lead to subsequent alterations in the immune response. The precise mechanisms underlying such vulnerability are poorly understood, but may be hypothesized to include changes in cytokine systems. Maternal separation was used as a model of exposure to early life stressors. Subsequent cytokine gene expression was studied using a cytokine gene expression array. Maternal separation resulted in significant down-regulation of the expression of 6 cytokine genes; chemokine ligand 7, chemokine receptor 4, interleukin 10, interleukin-1beta, interleukin 5 receptor alpha and integrin alpha M. Specific cytokines may be involved in mediating the effects of early adversity on subsequent immunosuppression. Further work is needed to delineate fully the relationship between early adversity, immune alterations, and behavioural changes.

The effects of vasopressin and oxytocin on methamphetamine-induced place preference behaviour in rats.

Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic pathway has been shown to be fundamental to the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been reported to play a vital role, with vasopressin exerting a long- term facilitatory effect and oxytocin exerting an inhibitory effect. Therefore we adopted a conditioned place preference model to investigate whether vasopressin V1b receptor antagonist SSR 149415 or oxytocin treatment would cause a decrease in the seeking behaviour in a reinstatement paradigm. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in place preference was not seen when vasopressin was administered during the extinction phase. On the other hand the methamphetamine-induced change in place preference was enhanced during the reinstatement phase in the animals that were treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Significant changes in dopamine levels were observed in some of our animals. Rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference behaviour in rats and that this change may be partially restored by vasopressin antagonism, but exaggerated by oxytocin.

Exercise partly reverses the effect of maternal separation on hippocampal proteins in 6‐hydroxydopamine‐lesioned rat brain

•  What is the central question of this study? Maternal separation exacerbates behavioural deficits induced by 6‐hydroxydopamine lesioning in a rat model of Parkinsons disease. In contrast, voluntary exercise reduces these effects due to compensation in the non‐lesioned hemisphere. We have asked how maternal separation and exercise affect protein expression in lesioned and non‐lesioned hemispheres of the rat brain. •  What is the main finding and its importance? Using isobaric tagging and quantification of peptides by matrix‐assisted laser desorption/ionization tandem mass spectrometry, we show that exercise and maternal separation have opposing effects on the hippocampus in the non‐lesioned hemisphere, with exercise partially reversing effects of maternal separation on the levels of energy metabolism and synaptic plasticity proteins.

The effects of lobeline and naltrexone on methamphetamine-induced place preference and striatal dopamine and serotonin levels in adolescent rats with a history of maternal separation

Exposure to early life stress has been suggested to increase an individual’s vulnerability to methamphetamine (MA) dependence. Although there is no cure for drug dependence, the opioid and vesicular monoamine transporter 2 (VMAT2) systems may be useful targets for treatment insofar as they play pivotal roles in the neurochemistry of addiction. Here we investigated the effects of naltrexone (opioid antagonist) and lobeline (VMAT2 inhibitor) on MA-induced place preference in adolescent rodents subjected to early life trauma (maternal separation, MS) and controls, as well as the effects on dopamine and serotonin levels in the striatum. We found: (1) maternal separation attenuated methamphetamine-induced place preference; (2) lobeline and naltrexone treatment had differential effects on serotonin and dopamine concentrations in the striatum, naltrexone increased serotonin levels in the maternally separated animals. The hypothesized effect of early adversity increasing MA-induced place preference may not be apparent in adolescence. However the data are consistent with the hypothesis that early life stress influences neurochemical pathways that predispose an individual to drug dependence.

Normative data for the Tygerberg Cognitive Battery and Mini-Mental Status Examination in a South African population.

BACKGROUND Normative data for the Tygerberg Cognitive Battery (TCB) and Mini-Mental Status Examination (MMSE) (in South Africa) have not been formally examined before. The TCB was developed for the bedside pen-and-paper screening of cognitive impairment in each of the 6 main cognitive domains, including attention and concentration, speech, memory, praxis, gnosis, and executive functioning. The test is also used to diagnose different neuropsychiatric conditions. The MMSE is an established screen of cognitive status, which is often used as a comparative standard for novel screening tests such as the TCB. The TCB was initially developed in English and Afrikaans, and a Xhosa version was also initiated with this study so that the 3 most common languages of the region could be accommodated. AIMS The first aim of the study was to estimate normative test performance on the TCB and MMSE among controls, and the second aim was to develop a Xhosa version of the TCB. METHODS Assessments of the TCB and MMSE were carried out in a population of healthy individuals (n = 157). In addition, healthy Xhosa-speaking participants (n = 14) were screened using a Xhosa version of the TCB. RESULTS Reliability scores for all forms of the TCB were satisfactory. Age and education correlated significantly with TCB scores (r = -0.26, P < .01; r = 0.64, P < .01, respectively), whereas only education significantly correlated with MMSE scores (r = 0.32, P < .05). Normative values were calculated accordingly, that is, controlled for the effects of age and education. The TCB scores also correlated significantly with MMSE scores (r = 0.49, P < .05), demonstrating the potential of the TCB to serve as an alternate cognitive assessment tool, along with the MMSE, to focus neuropsychiatric investigations. Scores on the Xhosa version differed significantly on speech, praxis, and gnosis between the Afrikaans and English participant scores. CONCLUSION These normative data can be used to increase precision and to provide an impartial evaluation when applying TCB to evaluate the cognitive ability of neuropsychiatrically impaired adult patients. However, age and education effects should be considered when computing the results of cognitive assessment.

Antidepressant-like effects of the aqueous macerate of the bulb of Gladiolus dalenii Van Geel (Iridaceae) in a rat model of epilepsy-associated depression

BackgroundIn Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy.MethodWe used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine.ResultsOur results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine.ConclusionThe results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is likely to be mediated by restoring the activity of the HPA axis and increasing the levels of BDNF in the hippocampus.

Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

Oleanolic acid is a triterpenoid that has been shown to possess antioxidant properties. In this study we investigated the effects of oleanolic acid in a parkinsonian rat model. Unilateral 6-hydroxydopamine (6-OHDA) lesions were carried out on postnatal day (PND) 60 in 4 groups viz. (1) Rats that started oleanolic acid treatment 7 days prior to lesion. (2) Rats not treated with oleanolic acid. (3) Rats that started oleanolic acid treatment 1 day post-lesion. (4) Rats treated with oleanolic acid 7 days post-lesion. The degree of forelimb impairment was assessed using limb use asymmetry and forelimb akinesia tests. Neurochemical changes were assessed using a Dopamine ELISA kit and mitochondrial apoptosis was measured using a mitochondrial apoptosis detection kit. In this study, animals injected with 6-OHDA displayed forelimb use asymmetry that was ameliorated by treatment with oleanolic acid 7 days pre- and 1 day post-lesion. In the cylinder test, rats injected with 6-OHDA favored using the forelimb ipsilateral (unimpaired) to the lesioned hemisphere while rats treated with oleanolic acid used the forelimb contralateral (impaired) to the lesioned hemisphere significantly more. Rats treated with oleanolic acid 7 days pre- and 1 day post-lesion had more dopamine in the striatum than the non-treated or the 7 days after lesion rats. Similarly, 6-OHDA-induced membrane depolarization was decreased in rats that received oleanolic acid treatment pre- or immediately post-lesion. This suggests that early treatment with oleanolic acid protects dopamine neurons from the toxic effects of 6-OHDA.