Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Aim: To determine the plasma neurotransmitters simultaneously and to find any correlation with pathological changes in the hippocampus and Purkinje cells and their relation with behavioral changes in Balb/c mice. Methodology: In the present study, both sexes of Balb /C mice were divided into two groups (4 males and 4 females; n = 8): Both the groups were given a single dose of either saline or sodium valproate (400mg kg-1) respectively through subcutaneous injection on PND 14. Behavioural tests were conducted on mice pups on various postnatal days till 40th day. On PND 41, blood samples were collected from all the animals for quantification of the neurotransmitters (serotonin, dopamine, and noradrenalin) in plasma, animals were sacrificed by cervical dislocation and whole brain was isolated for histological examination of the Purkinje cells and hippocampus. Results: Sodium valproate exposed animals showed loss of motor skill development (delayed negative geotaxic response), increased locomotor activity, increased anxiety, and retardation in water maze performance, and lower social interaction. Histopathological evolutions of cerebellum purkinje cells and hippocampus showed 40-50% atrophic cells in sodium valproate animals compared to control animals. Interpretation: The results of the present study indicate that Sodium valproate changes specific brain cell population in Balb/C mice, which might be the reason for the altered neurotransmitter levels, leading to behavioural changes in these animals.

Pharmacological Effect of Verapamil on Brain Oxidative Parameters and Mania-Like Behaviour in Paradoxical Sleep Deprived Mice

Although the implication of calcium signalling in the aetiology of anxiety remains elusive, drugs modulating calcium (like calcium channel blockers) have been discovered to be some worth beneficial as treatment option for anxiety related disorders. This study was therefore undertaken to assess probable ameliorative potential of verapamil against manic-like (stereotype behaviour) and anxiety-like symptoms in mice exposed to sleep deprivation. Mice were allotted into five treatment groups (n=5): group 1 and 2 received 10 mL/kg distilled water, groups 3 and 4 verapamil (25 and 50 mg/kg) while group 5 received astaxanthin (50 mg/kg) which served as the reference drug. Treatment was for 7 days and animals were sleep-deprived on the final 72 hours. Various behavioural tests to determine degree of stereotypical behaviour and locomotor activity were carried out. Anxiety test was done via the aid of a light/dark box and plus maze while stereotype behaviour was assess utilizing an open field box. Oxidative stress parameters; malondialdehyde and glutathione were assessed. Histopathological perturbations in the caudate putamen were also recorded. Data were subjected to ANOVA at α0.05. The results obtained suggest that verapamil significantly suppressed stereotyped behaviour and reduced the incidence of manic-like behaviour which was induced by paradoxical sleep deprivation. Verapamil also significantly restored antioxidant levels and protected against loss of caudate neurons. In conclusion, verapamil ameliorates manic-like symptoms and anxiety in mice derived of sleep, while protecting brain neurons against oxidative stress damage induced by sleep deprivation.

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behaviour and associated brain modulations is challenging. Here we tackled this question implementing a prism adaptation training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N=45) underwent VRPA (with a spatial shift either to the left/right side, or with no shift), and performed fMRI sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting state and free viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between large-scale cortical networks, namely attentional and default mode/fronto-parietal networks, only for adaptation groups. Additionally, VRPA was found to bias visual representations of naturalistic videos, as following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA induced after-effect measured in behavioural tests. This study demonstrates that a brief VRPA exposure is able to change large-scale cortical connectivity and correspondingly bias the representation of naturalistic sensory inputs.

Behavioural and molecular effects of alcohol in the stress model of zebrafish

Objectives: Stress and anxiety disorders are common health problems that have been related to an increase in the likelihood of developing addictions, which have individual and social consequences. Although socially acceptable, alcohol is a substance that can generate dependence and abuse. Alcohol misuse, its relationship with stress and its consequences have been studied; however, multiple limitations are placed on clinical research in humans. In this exploratory work, we analysed the behavioural and molecular effects of joint exposure to ethanol and an unpredictable stress protocol (USP) in adult zebrafish. Materials and Methods: Adult zebrafish behaviour was studied employing unpredictable stress and behavioural tests. The tests were performed in stressed and nonstressed animals with and without exposure to known concentrations of alcohol. To evaluate the behaviour, tracking techniques were used on video recordings and parameters such as distance travelled, swimming speed and place preference as well as aggression patterns with mirror proximity tests were measured. In the control and 0.75% alcohol group, the expression of candidate stress-related genes (slc6a4a, slc6a3, comta and bdnf3) was analysed by RT-qPCR. Results: The results showed that concentrations of 0.75% alcohol reduced the locomotor activity of the fish, which can be interpreted as an increase in the anxiolytic effect of alcohol under nonstress conditions. Expression of comta, bdnf3 and slc6a3 was reduced in the stress and stress plus 0.75% ethanol groups and expression of slc6a4a was increased in the stress plus 0.75% alcohol group. Conclusion: Our exploratory work contributes novel insights about the molecular and behavioural effects of the combination of unpredicted stress and alcohol misuse. The USP and ethanol exposure increase anxiety behaviour and reduce the expression of genes involved in brain homeostasis. Future study of other pharmacological compounds and additional genes will be helpful for a deeper understanding of the molecular mechanisms involved in the response to stress and alcohol use.

Shifting identities in the public sector: portraying the “new” public manager in the Italian setting

Purpose This paper aims to understand how training programs fostering discourses centred on individuals’ identity construction may turn resistance into a generative and enabling force to elicit more relationally and negotiated solutions of change. Design/methodology/approach The study used Foucault’s conceptualisation of “regimes of truth” to show how even potentially resistant public managers may generatively contribute to change processes if given the chance to restate the macro discourses of the hegemonic new public management movement at their own micro level. It relied upon an ethnographic approach based on verbal interviews, photo-elicitation, DiSC behavioural tests and observation of 29 Italian public managers participating in a training course. Findings The findings allow us to unveil how helping public managers to think about their self-identity in new ways enabled them to approach changing processes differently turning their resistance efforts into a generative force. Originality/value The paper offers a noteworthy contribution to the literature on public sector change by examining neglected issues relating to the identity of change agents and the implications of their multiple roles. It presents an alternative to the deterministic view of resistance as impeding or dysfunctionally shaping change under the new public management approach. This has important implications for both practice and policymaking.

Detecting Phase-Synchrony Connectivity Anomalies in EEG Signals. Application to Dyslexia Diagnosis

Objective Dyslexia diagnosis is a challenging task, since traditional diagnosis methods are not based on biological markers but on behavioural tests. Although dyslexia diagnosis has been addressed by these tests in clinical practice, it is difficult to extract information about the brain processes involved in the different tasks and, then, to go deeper into its biological basis. Thus, the use of biomarkers can contribute not only to the diagnosis but also to a better understanding of specific learning disorders such as dyslexia. In this work, we use Electroencephalography (EEG) signals to discover differences among controls and dyslexic subjects using signal processing and artificial intelligence techniques. Specifically, we measure phase synchronization among channels, to reveal the functional brain network activated during auditory processing. On the other hand, to explore synchronicity patterns risen by low-level auditory processing, we used specific stimuli consisting in band-limited white noise, modulated in amplitude at different frequencies. The differential information contained in the functional (i.e., synchronization) network has been processed by an anomaly detection system that addresses the problem of subjects variability by an outlier-detection method based on vector quantization. The results, obtained for 7 years-old children, show that the proposed method constitutes an useful tool for clinical use, with the area under ROC curve (AUC) values up to 0.95 in differential diagnosis tasks.

Colour Vision in Stomatopod Crustaceans: more questions than answers

Stomatopod crustaceans, or mantis shrimps, are known for their extensive range of spectral sensitivities but relatively poor spectral discrimination. Instead of the colour-opponent mechanism of other colour vision systems, the 12 narrow-band colour channels they possess may underlie a different method of colour processing. We investigated one hypothesis, in which the photoreceptors are proposed to act as individual wave-band detectors, interpreting colour as a parallel pattern of photoreceptor activation, rather than a ratiometric comparison of individual signals. This different form of colour detection has been used to explain previous behavioural tests in which low saturation blue was not discriminated from grey potentially because of similar activation patterns. Results here, however, indicate that the stomatopod, Haptosquilla trispinosa was able to easily distinguish several colours, including blue of both high and low saturation, from greys. The animals did show a decrease in performance over time in an artificially lit environment, indicating plasticity in colour discrimination ability. This rapid plasticity, most likely the result of a change in opsin (visual pigment) expression, has now been noted in several animal lineages (both invertebrate and vertebrate) and is a factor we suggest needing care and potential re-examination in any colour-based behavioural tests. As for stomatopods, it remains unclear why they achieve poor colour discrimination using the most comprehensive set of spectral sensitivities in the animal kingdom and also what form of colour processing they may utilise.

The influence of the stereotypic forms of activity in mice behaviour in standard behavioural tests

Laboratory animals often develop abnormal repetitive (stereotypic) behaviour that can influence both physiology and behavioural test results. Such abnormal behaviours usually develop in suboptimal environment and increase over time. To explore the development of stereotypic forms of activity night home-cage behaviour of laboratory mice was analysed and collated with the behaviour in open field (OFT), hole-board (HBT) and tail suspension (TST) tests twice within 16 weeks. Mice expressed few stereotypies and their duration lessened over time from median 8.2 to 1.0 %. In contrast, grooming behaviour increased significantly from 29.5 to 49.6 %. Home-cage grooming correlated with the latency of locomotion start in OFT and with the immobility time in TST. Intensity and stability of stereotypic activity and grooming inf­luenced the duration of grooming in OFT: the mice with unstable stereotypies groomed more than others, and mice with the lowes home-cage grooming level also groomed in OFT the most. Intensity and stability of night grooming influenced the behaviour in TST: the mice with unstable level of grooming were the most mobile in this test. Abnormal home-cage activity may indicate impaired welfare, and that, in turn, may affect test activity, so researchers need to keep it in mind when planning animal behaviour experiments.

Dexmedetomidine attenuates haemorrhage-induced thalamic pain by inhibiting the TLR4/NF-κB/ERK1/2 pathway in mice

Background Thalamic pain, a neuropathic pain syndrome, frequently occurs after stroke. This research aimed to investigate the effect of dexmedetomidine (DEX) on thalamic pain. Methods The cellular localization of the TLR4 protein was determined by immunostaining. The expression of Iba1, GFAP and protein associated with the TLR4/NF-κB/ERK1/2 pathway was measured by Western blotting. Continuous pain hypersensitivity was evaluated by behavioural tests. The results were analysed by one-way ANOVA, two-way ANOVA and Tukey’s post hoc test. Results The results demonstrated that DEX obviously alleviated thalamic pain induced by haemorrhage on the ipsilateral side and delayed the development of pain hypersensitivity. Furthermore, the expression levels of Iba1, GFAP and proteins associated with the TLR4/NF-κB/ERK1/2 signalling pathway were greatly increased in mice with thalamic pain, but these effects were reversed by DEX. Conclusion Our findings suggest that DEX alleviates the inflammatory response during thalamic pain through the TLR4/NF-κB/ERK1/2 signalling pathway and might be a potential therapeutic agent for thalamic pain.

Galanin(1-15) Potentiates the Antidepressant-like Effects Induced by Escitalopram in a Rat Model of Depression

Selective 5-HT reuptake inhibitor antidepressants (SSRIs) are the first choice in major depressive disorder (MDD), but 50% of affected patients do not show improvement. Galanin(1-15) [GAL(1-15)] enhanced Fluoxetine antidepressant-like effects in an animal model of depression, the olfactory bulbectomy (OBX); however, further detailed analysis of GAL(1-15) effects as augmentation treatment in OBX rats are needed. In OBX rats, we analysed the effect of GAL(1–15) on Escitalopram (ESC)-mediated responses in behavioural tests related to despair. We studied whether GAL(1–15) effects involved 5-HT1AR using an in vivo model siRNA 5-HT1A knockdown rats. Moreover, we analysed by immunohistochemistry the expression of the immediate-early gene c-Fos (c-Fos IR) after the administration of GAL(1-15)+ESC in OBX rats in several nuclei involved in MDD. GAL(1-15) enhances the antidepressant-like effects of ESC, and the GALR2 antagonist M871 blocked GAL(1-15) mediated actions. The downregulation of 5-HT1AR by siRNA was sufficient to block GAL(1-15) effects. Our immunohistochemistry and principal component analysis (PCA) analysis suggest that two functional networks are involved in these effects; one includes the lateral (LHb) and medial (mHb) habenula, dorsal raphe (DR) and ventral tegmental area (VTA), and the other consists of the dentate gyrus (DG), and prefrontal cortex (PFC). The results open up the possibility of using GAL(1-15) in combination with SSRIs as a novel strategy for treating MDD.