JULIDE: A Software Tool for 3D Reconstruction and Statistical Analysis of Autoradiographic Mouse Brain Sections

In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool

The effects of MDMA on brain: An in vivo study in rats

Background and objective : 3, 4-Methylenedioxymethamphetamine (MDMA) is a powerful central nervous system stimulant that acts by increasing the activity of several neurotransmitter systems. This study aimed to investigate the effect of different doses of MDMA on the level of serotonin in the brain measured from the cerebrospinal fluid (CSF) and their effects on the neurons. Materials and methods : Twenty-six adult male rats were divided into 4 groups. The control group (n=7) received intraperitoneal (IP) injections of 1 mL/gm normal saline twice daily for one week. The MDMA treated groups (n= 6/7) were further subdivided into 3 groups, each receiving 5, 10 or 15mg/kg MDMA intraperitoneal (IP) injections twice daily for one week ; respectively. 24 hours after the last injection of the rats, the CSF was collected. The brains were dissected and processed for paraffin sections and stained by cresyl etch violet stain. Histology, morphometry and statistical analysis were done. Results : The administration of different doses of MDMA significantly increased the level of serotonin in comparison with the control group. The morphometry study indicated that the number of intact neurons in the hippocampus significantly decreased following the administration of different doses of MDMA comparing to the control group. The results also indicated that there was a strong negative correlation between the serotonin levels and the number of intact neurons. Conclusion : MDMA administration even at a low dose had degenerative effects on the neurons in the hippocampus as evidenced by morphometric study, and the intake should be avoided

Effetti di un trattamento cronico con fluoxetina nel recupero della memoria spaziale e della plasticita' sinaptica ippocampale in un modello murino della sindrome Down

La presente Tesi di Laurea intende investigare gli effetti di un trattamento cronico con fluoxetina nel recupero delle disfunzioni mnemoniche e di plasticità sinaptica ippocampale nel topo Ts65Dn. La fluoxetina è un inibitore selettivo del reuptake della serotonina attualmente utilizzato come trattamento farmacologico standard per numerose patologie psichiatriche. Nella prima parte della Tesi ho eseguito uno studio volto a stabilire un dosaggio appropriato per minimizzare il rischio di effetti collaterali. Precedenti studi hanno dimostrato come la fluoxetina abbia un'azione pro-convulsivante in modelli animali; inoltre, un dosaggio elevato di tale farmaco può essere responsabile di crisi di tipo epilettico anche nell'uomo. Tramite un’indagine dose-effetto ho potuto stabilire che il dosaggio di 10 mg/Kg/die si dimostra sicuro nei topi Ts65Dn, non lasciando registrare nessun caso di attacchi convulsivi o morti improvvise. Nella seconda parte della Tesi, ho quindi potuto valutare gli effetti di un trattamento cronico con fluoxetina al dosaggio precedentemente stabilito; la fluoxetina è stata somministrata nell’acqua da bere per 8 settimane. I risultati hanno mostrato che tale trattamento consente un recupero delle abilità di memoria spaziale e della plasticità sinaptica ippocampale nei topi Ts65Dn adulti. Complessivamente, i risultati riportati nella presente Tesi di Laurea suggeriscono una possibile applicazione clinica della fluoxetina nel trattamento delle disfunzioni fenotipiche associate alla sindrome di Down

Implicación de la vía kinurenina en los efectos inmediatos y a largo plazo inducidos por 3,4-metilendioximetanfetamina (MDMA, éxtasis) en cerebro de rata

MDMA es un derivado anfetamínico con actividad psicotropa que afecta principalmente al sistema serotoninérgico [1]. Numerosos trabajos han descrito que la administración de dosis neurotóxicas de MDMA disminuye la concentración de serotonina (5-HT) y la densidad de los transportadores de 5-HT (SERT) en el hipocampo y la corteza frontal [2-5]. Este efecto neurotóxico está estrechamente relacionado con el estrés oxidativo generado de forma inmediata tras la administración de la droga, ya que se ha observado una disminución del daño serotoninérgico inducido por MDMA tras la administración de atrapadores de radicales libres y otras sustancias antioxidantes [6-8]..

Characterisation of the Superior Colliculus in a Rat Model of Attention Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioural disorder of childhood onset. Core symptoms include hyperactivity, impulsivity and inattention. Despite high prevalence and effective pharmacological treatment, the pathophysiology is poorly understood. Present theories of the etiology of ADHD suggest a crucial influence of dopamine. To date, little investigation has focussed on structures upstream of dopamine neurons which could cause these abnormalities. The midbrain superior colliculus (SC) is conserved across species and plays a role in saccade generation, visual saliency and attention. Evidence suggests that the SC could be dysfunctional in ADHD, and may explain core symptoms of ADHD, providing a site for action of therapeutic treatments. The spontaneous hypertensive rat (SHR), an animal model for ADHD has shown face validity, construct validity and predictive validity, and is the most commonly used animal model of ADHD. Understanding the etiology of the ADHD-like behaviours in the SHR is important in improving our understanding of the etiology of ADHD itself. This thesis presents work that demonstrates that the SHR responds to visual and auditory stimuli in a different way behaviourally and physiologically compared to two control strains, with these differences likely to be mediated by alterations within and upstream of the SC, respectively, resulting in altered saliency of sensory stimuli. These results are compatible with the two unifying theories of ADHD, but suggest that the dysregulation of dopamine is secondary to changes upstream in the SC and structures projecting to it. The findings of slower onset latency in the SHR are also in line with ADHD and the ADHD-like behaviours seen in the SHR and support ADHD being a development disorder. ADHD treatments such as amphetamine and fluoxetine may have a mechanism of action within the SC, and therefore normalise the exaggerated response, yet the results from the current experiment on drug effects are inconclusive