Paolo Fabene

Camillo Golgi discovered, in 1898, the cell organelle that has been called, after him, "the Golgi apparatus" or "the Golgi complex." Because of the necessity of saving words in scientific literature, "the Golgi apparatus" is nowadays frequently referred to only as "the Golgi" or used in an adjectival form in combination with a variety of terms (e.g., Golgi vesicle, Golgi area, Golgi traffic, and so forth). We present here a search of the Medline database for the years 1967 through 1997, which demonstrates that the eponym has lost all connection with Golgi's personal identity. In addition, the search indicates that interest in the Golgi apparatus is steadily increasing, as evidenced in the scientific literature, and that Golgi's name is much more frequently used in association with the cell organelle than with any of the other scientific contributions of this scientist, including the Golgi impregnation of nerve cells.

Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity. Chronic treatment with fingolimod (3 mg kg(-1), i.p., once a day for 4 weeks) reduced the immobility time in the forced swim test (FST) in a large proportion of CUS mice. This treatment also caused anxiogenic-like effects in the social interaction test without affecting anxiety-like behavior in the elevated plus maze or spatial learning in the water maze. CUS mice showed reduced BDNF levels and enhanced HDAC2 levels in the hippocampus. These changes were reversed by fingolimod exclusively in mice that showed a behavioral response to the drug in the FST. Fingolimod treatment also enhanced H3 histone K14-acetylation and adult neurogenesis in the hippocampus of CUS mice. Fingolimod did not affect most of the parameters we have tested in unstressed control mice. The antidepressant-like activity of fingolimod was confirmed in mice chronically treated with corticosterone. These findings show for the first time that fingolimod exerts antidepressant-like effect acting in a "disease-dependent" manner, and raise the interesting possibility that the drug could relieve depressive symptoms in MS patients independently of its disease-modifying effect on MS.

ABSTRACT Preclinical applications in neuroradiology are rapidly growing. This work briefly reviews the aims, methods and research fields in which preclinical neuroradiology units are involved. Specifically we will describe applications in pharmacological research, transgenic animals phenotyping, stem cell imaging and molecular imaging. The interdisciplinary approach, typical of preclinical neuroradiology, appears to be useful also in the training of young neuroradiologists.

To assess the effect of mild forced physical training on cognitive and locomotory behavior in old (26 mo.) mice. Randomized, controlled study. Open-field in the behavioral laboratory. Sixteen old sedentary male mice randomly assigned to one of two groups, exercise (E) or rest (R). group E underwent treadmill running for one month at moderate intensity (belt speed=8 m/min, 45 min, five days a week), group R was only allowed spontaneous locomotor activity. exploratory and locomotor behavior were evaluated in an enriched environment (Ethovision recording). motor patterns were significantly reduced (chi2 test, p<0.05) in the E vs R group after one month of training; exploratory patterns were not different, both groups showing modest exploratory activity. mild forced physical training initiated at old age may have detrimental effect on motor behavior in male mice without improving cognitive parameters.

The rat brain was investigated with structural and functional magnetic resonance imaging (MRI) 12 h after the arrest of pilocarpine-induced status epilepticus lasting 4 h. Histopathological data, obtained immediately after MRI analysis, were correlated with the images through careful evaluation of tissue shrinkage. Diffusion-weighted and T2-weighted imaging showed changes throughout the cerebral cortex, hippocampus, amygdala, and medial thalamus. However, only T2-weighted imaging, based on rapid acquisition relaxation-enhanced sequences, revealed in the cortex inhomogeneous hyperintensity that was highest in a band corresponding to layer V. Regional cerebral blood volume (rCBV) maps were generated using T2*-weighted gradient-echo images and an ultrasmall superparamagnetic iron oxide contrast agent. In the cortex, rCBV peaked in superficial and deep bands exhibiting a distribution complementary to the highest T2-weighted intensity. Selective rCBV increase was also documented in the h...

Altered perceptual and emotional processing might bind impaired cognitive mechanisms during aging; however the nature of these sensory perception modifications is still unknown. In the present experiment we analyzed in rats, from early to mature life (2 to 11 months old), the response to unattended auditory evoked stimulation (Auditory evoked potential, AEP) and the power spectrum of spontaneous electroencephalogram (EEG), with the aim of unraveling the onset and target functional effects of aging. Somatosensory and cingulate cortex, mediodorsal thalamus and CA3 hippocampus were chosen for examination based on their involvement in sensory processing and age-related deficits. The main finding of this study is the early onset of age-related changes in adult rats as can be established with both AEP's and frequency analyses, and its diversity between brain regions during normal aging.

Epilepsy is a chronic disorder that affects 1% of the world population and is characterized by chronically reoccurring seizures. Seizures are initiated by abnormal excessive or synchronous neuronal activity in the brain. Epilepsy requires life long anti-convulsant therapy and current therapies for epilepsy selectively target neuronal activity. In the last decade, cytokines and vascular alterations have been discussed in relation to the pathogenesis of epilepsy, suggesting a potential role for inflammation mechanisms in seizure induction. More recently, it has been shown that leukocyte trafficking plays a key role in seizure generation, and that anti-leukocyte adhesion therapy has therapeutic and preventative effects in an experimental model of human epilepsy. These results were supported by evidence in humans showing that leukocytes accumulate in the brain parenchyma of patients with different types of epilepsy. Finally, recent clinical observations suggest that therapies able to interfere with leukocyte trafficking may have a therapeutic effect in epilepsy. The emerging role for leukocytes and leukocyte adhesion mechanisms in seizure generation provides insight into the mechanisms of brain damage and may contribute to the development of novel therapeutic strategies in epilepsy.

The combined evaluation of physiology and behaviour allows a complete and more comprehensive pre-clinical assessment of central nervous system (CNS) function. An integrated video-telemetric electroencephalography (Video-tEEG) system, which allows the simultaneous and continuous recording of EEG and video images for long periods, was developed. This study focuses on the refinement of the surgical methodology for the combined recording of cortical, hippocampal EEG and electromyogram (EMG) waveforms in freely moving rats. The post-operative recovery of animals was monitored by recording EEGs by telemetry and the general activity by video, on days 1, 6 and 15 after surgery, for approximately 24h, on each occasion. The results suggested that the applied surgical technique for the implantation of the telemetric transmitter, allowed for a gradual recovery of the animals within 15days. During the recovery period the behavioural and locomotor parameters measured, indicated that there were no changes to the light-dark circadian cycle, and these parameters gradually tended to reach background levels within a 15-day period. Using a mechanical connection between the deep and the telemetric electrodes, 15days after surgical implantation the recording system was able to acquire cortical and hippocampal EEG traces of good quality. This present study is concerned with the refinement of the surgical technique, as well as the integration and synchronisation of the commercially available Dataquest telemetry system and the Noldus video system, in order to study cortical, hippocampal EEG waveforms, in combination with behaviour and locomotion. The application of this integrated Video-tEEG system could provide advantages in the ethical use of animals in different pre-clinical research areas.

In order to investigate epilepsy, that is one of the most common neurological disorders, in the last decades different animal models have been proposed. Prevention, diagnosis, treatment and basic knowledge have been improved by the mean of these models. Numerous animal models have been developed in epilepsy research, both for generalized and for simple/complex partial seizures. Animal models for generalized seizures include sensory (light, noise, movement, etc) or electrical stimulations and genetic models. Models for focal seizures include topical or systemic application of pro-convulsive compounds or electrical stimulation. Baboons, mice, rats, rabbits, and Fayoumi chicken have been extensively used in this regard. Since 1983, when magnetic resonance spectroscopy was used to evaluate for the first time in vivo alterations induced by status epilepticus in rabbit, an increasing interest for the neuroimaging perspective has led to new insights in the study of epileptic disorders. In the early 1990s experimental studies provided evidence for the feasibility of magnetic resonance imaging analysis and detection of tissue damage in kainic acid-induced epilepsy in rat. In the following years a wealth of data has been obtained by the mean of functional MRI and/or by diffusion-weighted images. The studies reported in the literature of the last decades indicate in vivo magnetic resonance of epilepsy model as valuable and extremely informative tool.