Giorgio Vivacqua

Sapienza University of Rome, Roma, Latium, Italy

Are you Giorgio Vivacqua?

Claim your profile

Publications (6)11.89 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropiridine (MPTP) is a neurotoxin, widely used to produce experimental models of Parkinson Disease in rodents and primates. Although dopaminergic neurons are the most sensitive to MPTP neurotoxicity, different neuronal subtypes are affected. Among these, recent studies indicate that MPTP may produce pathological effects on spinal neurons. In fact, MPTP activates apoptotic proteins within the spinal cord and in particular within the motor neurons, suggesting commonalities between Parkinson Disease and Amyotrophic Lateral Sclerosis. In order to assess this point, in the present study we measured whether MPTP produces motor neurons loss. We chose a dose of MPTP (20 mg/kg × 3, 2 h apart), which in C57BL/6N mice was able to induce a massive nigrostriatal damage. Since both Parkinson Disease and Amyotrophic Lateral Sclerosis are characterized by altered alpha-synuclein immunostaining, this protein was also evaluated within spinal motor neurons, following MPTP administration. Three different monoclonal antibodies, recognizing distinct epitopes in the sequence of alpha-synuclein were used. Severe dopaminergic cell loss was quantified by stereology within the substantia nigra pars compacta, along with marked decrease of striatal tyrosine hydroxylase densitometry. The same doses of MPTP also caused a significant motor neuron loss in the spinal cord (roughly 30%). Spared motor neurons appeared often dysmorphic and vacuolated and possessed altered alpha-synuclein immunostaining. This latter finding extended to other cell types of the spinal cord. These data indicate that MPTP, apart from being a dopaminergic neurotoxin, produces also motor neuron death, thus bridging experimental Parkinsonism and motor neuron disease.
    Journal of chemical neuroanatomy 05/2012; 44(2):76-85. · 1.75 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Alpha-synuclein is a 140 amino acids' protein, widely expressed in the nervous system of different vertebrates and closely related with several neurodegenerative disorders. Although its pathological involvement is reported from long time, its physiological function and its role in neurodegeneration is not yet clear. Disposing of two new monoclonal antibodies, able to detect alpha-synuclein in different compartments of the neurons, the aim of this study is to create an anatomical map of the protein's distribution in the central nervous system of C57 BL\6J mouse, the mouse strain most sensitive to 1-methyl 4-phenyl 1,2,3,6-tetrahydro pyridine neurotoxicity and widely used to apply toxic models of Parkinson disease. The two monoclonal antibodies confirm their ability in visualizing the protein in distinct compartments of the neurons, since 2E3 detects alpha-synuclein in the nerve cells' fibers, whereas 3D5 preferentially in the neuronal nuclei. Both antibodies, instead, are able to show alpha-synuclein at the synaptic terminals. The protein is ubiquitary distributed in the brain, as well as in the spinal cord, but its sub-cellular localization differs markedly in the various regions of the central nervous system. Among alpha-synuclein immunoreactive territories, we describe a particular organization in habenular nuclei, dorsal hippocampus, olfactory bulbs, brain stem nuclei and cerebellar cortex. This preliminary immunohistochemical study, provides the first anatomical map of the alpha-synuclein distribution in the C57 BL\6J mouse CNS and suggests that alpha-synuclein is differentially localized, at sub-cellular level, in different types of neurons and that, therefore, it can plays a specific role for each neuronal subtype. Our study in healthy C57 BL/6J mice represents a starting point to analyze the variations in the overall distribution of alpha-synuclein in mouse models of Parkinson disease.
    Journal of chemical neuroanatomy 03/2011; 41(2):97-110. · 1.75 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The involvement of the spinal cord in parkinsonism is becoming more and more evident based on human autopsies and on experimental models, obtained using specific neurotoxins or genetic manipulations. Besides Parkinson disease, other degenerative disorders characterized by parkinsonism, involve the spinal cord, and multiple neurotransmitters, apart dopamine, are altered in parkinsonism, also in their spinal projections. In the present review we discuss spinal cord pathology of different genetic or toxic experimental models of parkinsonism, as well as the neuropathological reports from autoptic cases of sporadic Parkinson disease and of other neurodegenerative conditions, overlapping with parkinsonism. Furthermore, anatomical distribution of alpha-synuclein in the spinal cord and coeruleo-spinal projections are reviewed, at the light of their possible involvement in spinal neurons degeneration. All these evidences call for an anatomical stemmed novel approach to understand specific features of parkinsonism, which might be due to such an involvement of the spinal cord. Moreover they suggest a common neurodegenerative process, underlying distinct neurodegenerative disorders, to which spinal neurons could be the more sensible.
    Journal of chemical neuroanatomy 03/2011; 42(4):327-40. · 1.75 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Previous studies suggest that behavioral consequences of heroin treatment depend on the drug history of the animals and that cholinergic neurotransmission is involved in both behavioral and motor sensitization induced by heroin and other drugs of abuse. Immunohistochemistry, using a recently developed antiserum, specific for choline acetyl-transferase of the common type (cChAT), was applied to four different groups of rats, differing in drug regimens. Two groups of rats were submitted to the same schedule of heroin sensitization and then challenged for vehicle or heroin before sacrifice, obtaining two distinct groups, namely heroin-vehicle (HV) and heroin-heroin (HH). The same challenge was applied to another group of rats, previously submitted to a treatment with vehicle, obtaining other two groups, vehicle-vehicle (VV) and vehicle-heroin (VH), respectively. The number of cChAT-positive neurons is significantly increased (p<0.05) in the diagonal band nuclei (with a consequent increase of cChAT positive fibers in the dentate gyrus) and notably, even not significantly (p>0.05), increased in the nucleus accumbens core of heroin-sensitized rats (HV, HH). Instead, acute heroin treatment significantly increase (p<0.05) the number of cChAT-positive cells in the nucleus accumbens shell of both heroin-naïve (VH) and heroin-sensitized (HH) rats. In heroin-sensitized rats (HV, HH), moreover, staining intensity of cChAT-positive fibers is significantly increased in the dorsal striatum, and basolateral amygdala (p<0.05). Unlikely, cChAT positive fibers in the central amygdala are significantly increased (p<0.05) by acute heroin treatments (VH, HH). The increase of cholinergic fibers in the dentate gyrus of the heroin sensitized rats (HV, HH) seems accompanied by a evident reduction in calretinin immunoreactive neurons in the same area. Our results, in a small group of animals, support the view that cholinergic mechanisms are intimately associated with the development of addictive phenotype. Furthermore, they suggest that cholinergic system is differentially engaged, following different heroin treatments.
    Journal of chemical neuroanatomy 03/2011; 41(2):111-21. · 1.75 Impact Factor
  • Furong Cheng, Giorgio Vivacqua, Shun Yu
    [show abstract] [hide abstract]
    ABSTRACT: Alpha-synuclein (α-syn), a synaptic protein richly expressed in the central nervous system, has been implicated in several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies, which are collectively known as synucleinopathies. By contrast to the clear evidence for the involvement of α-syn in synucleinopathies, its physiological functions remain elusive, which becomes an impediment for revelation of its pathological mechanism. Since α-syn is richly expressed in presynaptic terminals and associated with synaptic vesicles, a large number of studies have been focused on revealing the potential functions of this protein in neurotransmission and synaptic plasticity. In this review article, we summarized recent advances for the role of α-syn in synaptic vesicle recycling, neurotransmitter synthesis and release, and synaptic plasticity. We discussed the possible relevance between the loss of normal α-syn functions in disease conditions and the onset of some neurodegenerative diseases.
    Journal of chemical neuroanatomy 12/2010; 42(4):242-8. · 1.75 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: This study provides the first immunohistochemical evidence of the presence and distribution patterns in the rat spinal cord of alpha-synuclein (alpha-Syn), a soluble acidic protein, widely expressed in the CNS and closely associated to the pathogenesis of neurodegenerative conditions such as Parkinson's and Alzheimer's diseases. We used two novel homemade monoclonal antibodies (2E3 and 3D5) recognizing two different epitopes of alpha-Syn. Both antibodies localized alpha-Syn within the nerve terminals, whereas 3D5 alone also localized it within the neuronal nuclei. alpha-Syn-immunoreactive nervous elements were widely recognized throughout rat spinal cord and in almost all the gray matter laminae. However, they appeared particularly concentrated within laminae I, II, VII and X and more scattered in the others. Double immunofluorescent labeling showed that alpha-Syn colocalized with synaptophysin in the presynaptic nerve terminals, with neuropeptide Y (NPY) in lamina I, II, IX and X, and had close relationships with tyrosine hydroxylase (TH) immunoreactive neurons in laminae VII and X. Interestingly, the alpha-Syn-immunoreactive nerve elements, in lamina X, contained little of calbindin-28KD and calretinin-31KD. Our findings could help in understanding the genesis of some early clinical symptoms of Parkinson's disease (PD), such as pain and dysautonomic disorders, and indicate the spinal cord as their probable starting point, according to the ascending theory of PD, proposed by Braak.
    Neuroscience 01/2009; 158(4):1478-87. · 3.12 Impact Factor