Clelia Pellicano

Neuropharmacology and behavior in planarians: Translations to mammals

Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates.

The Dopaminergic System in Peripheral Blood Lymphocytes: From Physiology to Pharmacology and Potential Applications to Neuropsychiatric Disorders

Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency. The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug- or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments.

Intensity-dependent facial emotion recognition and cognitive functions in Parkinson's disease

Patients with Parkinsons disease (PD) frequently display non-motor symptoms. In this study, we investigated intensity-dependent facial emotion recognition in patients with PD and healthy controls (HC), matched for age, gender, and education, and its relationship to individual cognitive domains. Seventy patients with PD and 70 HC were submitted to a clinical, neuropsychological, and psychopathological evaluation. Facial emotion recognition performance was assessed using the Penn Emotion Recognition Test (PERT). The patients with PD recognized fewer low- and high-intensity facial expressions of disgust than HC. This effect was selective, because their global ability to recognize emotions was intact. Both patients with PD and HC recognized high-intensity better than low-intensity emotions, except for disgust, which was recognized better at low intensity. In the patients with PD, overall facial emotion recognition and selective disgust recognition performances were related to deficits in many neuropsychological domains (verbal and visuo-spatial memory, attention, praxis, and verbal fluency). The ability to recognize emotions is a complex cognitive process requiring the integrity of several functions. Therefore, it is likely that structural or functional derangement of the discrete neural pathways involved in these cognitive functions in patients with PD makes it difficult for them to recognize emotions expressed by others.

Minocycline in amyotrophic lateral sclerosis: a pilot study.

Recent studies indicate that minocycline exerts neuroprotective effects in vitro and in vivo, and suggest that the drug may represent a novel therapeutic approach to amyotrophic lateral sclerosis (ALS). In this study we investigated the safety of combined treatment with minocycline and riluzole in ALS. Twenty ALS patients were randomised into two groups and administered either riluzole (50 mg b.i.d.) or riluzole and minocycline (100 mg i.d.) for 6 months. Disease progression was measured by means of the ALS-Functional Rating Scale score at monthly intervals. Respiratory function was measured at the beginning of the study and repeated after 3 and 6 months of treatment. Combined treatment with minocycline and riluzole was not followed by significant side effects. This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment.

Dopamine transporter immunoreactivity in peripheral blood lymphocytes discriminates Parkinson’s disease from essential tremor

SummaryPeripheral blood lymphocytes (PBL) provide a model to study the changes of neurotransmitter-receptor systems in neurodegenerative disorders, including Parkinson’s disease (PD). In this study, densitometric analysis was applied to measure dopamine transporter (DAT) immunoreactivity in PBL from dopaminergic drug-free patients suffering PD or essential tremor (ET) with respect to healthy subjects. The results showed a significant reduction of DAT immunoreactivity in PBL in PD but not in ET. These finding suggests that DAT immunoreactivity in PBL may discriminate between PD and ET in the early clinical stages.

Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system.

Sociodemographic, neuropsychiatric and cognitive characteristics of pathological gambling and impulse control disorders NOS in Parkinson׳s disease

Despite of previous evidence supporting the association between impulse control disorder (ICD) and several demographic, clinical and therapeutic features in Parkinsons disease (PD), the relationships between pathological gambling (PG) or other variants of ICD (ICD-NOS) and specific neuropsychiatric or cognitive domains are not entirely defined. In this study, 155 PD patients without dementia or cognitive impairment underwent: i. the ICD diagnoses, using the Questionnaire for Impulsive-Compulsive Disorders, ii. the mood and anxiety disorders diagnoses, according to the DSM-IV-TR criteria, and iii. a comprehensive battery for measuring severity of psychopathology and neuropsychology domains. Patients were divided in those with pathological gambling (PG), ICDs not otherwise specified (ICD-NOS), or the lack of ICD (No-ICD). There was a progression in age and age at onset from the younger PG subjects throughout ICD-NOS to No-ICD. PG and ICD-NOS subjects had longer disease duration and were taking significantly higher dosages of antiparkinsonian drugs than No-ICD ones. PG subjects had significantly higher severity of depressive and anxious symptoms with respect to the other 2 groups. Both PG and ICD-NOS subjects suffer from increased severity of psychotic symptoms than No-ICD ones. The 3 groups did not differ in any cognitive measure. Our results support the concept that the different sociodemographic and neuropsychiatric profiles of PD patients are associated with different ICDs. Moreover, we clearly demonstrate the lack of relationship between ICD and cognitive performances in undemented PD patients.

Regional cortical thickness and cognitive functions in non-demented Parkinson's disease patients: A pilot study

Background and purpose:  The pathology of neuropsychological deficits in Parkinson’s disease (PD) is incompletely defined.

Neuropsychiatric and cognitive symptoms and body side of onset of parkinsonism in unmedicated Parkinson's disease patients.

INTRODUCTION The onset of motor symptoms is primarily unilateral in the majority of Parkinsons disease (PD) patients. Because of the lateralization of several cognitive and neuropsychiatric functions and the role of impaired dopaminergic transmission on non-motor symptoms in PD, the question raises whether body side of onset of parkinsonian motor symptoms might influence cognitive and/or neuropsychiatric domains in idiopathic PD. METHODS Here we investigated the prevalence and severity of neuropsychiatric and cognitive alterations in a cohort of 84 drug naïve PD patients, divided into two groups according to the body side of onset of motor symptoms (42 left onset PD patients-LPD and 42 right onset PD patients-RPD). Eighty-four age-, sex- and educational level-matched healthy subjects (HC) served as controls. RESULTS Both LPD and RPD patients had higher prevalence and severity of neuropsychiatric and cognitive symptoms with respect to HC. There were no difference between LPD and RPD as to the pattern or severity of neuropsychiatric and cognitive symptoms. However, significantly higher percentage of LPD patients than RPD deviated more than 1.5 SD from mean values of HC at scales for depression. CONCLUSIONS Our results indicate that in early PD patients side of onset of parkinsonian motor symptoms does not influence non-motor accompanying signs, at least at neuropsychiatric and neuropsychological domains, and suggest that differences reported by previous reports may be secondary to disease progression and/or dopamine replacement therapy.

Central and peripheral dopamine transporter reduction in Parkinson's disease

Abstract Objective: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinsons disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinsons disease. Methods: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of 123I-fluopane single-photon emission computed tomography in the same patients. Results: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. Discussion: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinsons disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.