Background: Missense mutations and multiplications of the α-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). α-Synuclein protein is also a major component of Lewy bodies, the hallmark pathological inclusions of PD. Therefore, α-synuclein plays an important role in the pathogenesis of familial and sporadic PD. To model α-synuclein-linked disease in vivo, transgenic mouse models have been developed that express wild-type or mutant human α-synuclein from a variety of neuronal-selective heterologous promoter elements. These models exhibit a variety of behavioral and neuropathological features resembling some aspects of PD. However, an important deficiency of these models is the observed lack of robust or progressive nigrostriatal dopaminergic neuronal degeneration that is characteristic of PD. Results:We have developed conditional α-synuclein transgenic mice that can express A53T, E46K or C-terminally truncated (1-119) human α-synuclein pathological variants from the endogenous murine ROSA26 promoter in a Cre recombinase-dependent manner. Using these mice, we have evaluated the expression of these α-synuclein variants on the integrity and viability of nigral dopaminergic neurons with age. Expression of A53T α-synuclein or truncated αSyn119 selectively in nigrostriatal pathway dopaminergic neurons for up to 12 months fails to precipitate dopaminergic neuronal loss in these mice. However, αSyn119 expression in nigral dopaminergic neurons for up to 12 months causes a marked reduction in the levels of striatal dopamine and its metabolites together with other subtle neurochemical alterations. Conclusion:We have developed and evaluated novel conditional α-synuclein transgenic mice with transgene expression directed selectively to nigrostriatal dopaminergic neurons as a potential new mouse model of PD. Our data support the pathophysiological relevance of C-terminally truncated α-synuclein species in vivo. The expression of αSyn119 in the mouse nigrostriatal dopaminergic pathway may provide a useful model of striatal dopamine depletion and could potentially provide a presymptomatic model of PD perhaps representative of the earliest derangements in dopaminergic neuronal function observed prior to neuronal loss. These conditional α-synuclein transgenic mice provide novel tools for evaluating and dissecting the age-related effects of α-synuclein pathological variants on the function of the nigrostriatal dopaminergic pathway or other specific neuronal populations.

A surgically resected medulloblastoma of the left cerebellum in a 42-year-old man contained numerous mature fat cells; many of these adipocytes expressed glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin as seen by immunocytochemistry. The cellular parts of the tumor showed varying immunoreactivities for GFAP, S-100 protein, neuron-specific enolase, and synaptophysin. It is concluded that this tumor exhibits a unique spectrum of differentiation along multiple lines, including transformation of neuroectodermal cells to fat cells. The significance of this new type of differentiation in primitive neural tumors remains to be elucidated.

The central nervous system (CNS) was studied in 252 HIV-infected patients from the States of Rio de Janeiro and São Paulo in Brazil, the regions with the highest incidence of AIDS in the country. We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases. There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or tumours. Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections. The most frequent was toxoplasmosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%). Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7%. Other opportunistic and HIV associated lesions were present in a limited number of cases and there were also vascular and non-specific lesions. Our study confirms the high frequency of CNS lesions in HIV infected patients. They are morphologically similar to those previously described. However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV-associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio-economic factors.

Morphological changes in the myocardium after left ventricular hypertrophy, due to chronic experimental hypertension, require an understanding of the quantitative relationship between myocyte and nonmyocyte compartments forming the structural framework of the myocardium. Hypertension was induced by long-term low-dosage inhibition of nitric oxide synthesis by N^G-nitro-L-arginine methyl ester (L-NAME) in rats. L-NAME (12 mg/kg) was given to animals in water ad libitum during 15 weeks. After this period, systolic blood pressure increased almost 50% as compared with that in the control group. Morphological changes in control and L-NAME animals were investigated with stereology and immunohistochemistry. Comparing control and L-NAME animals, the surface density of myocytes decreased 73.7% while the mean cross-sectional area increased 97.6% in L-NAME rats. The volume density of myocytes decreased 45.9% and the volume density of the interstitium increased 71.7% in L-NAME rats. No stereological difference was found in blood vessels comparing the two groups. Remodeling of the cardiac interstitium occurred with increased deposition of both fibronectin and type III collagen. Fibronectin was seen in both early and latter responses to infarction while type III collagen was seen mainly in areas of incomplete healing among myocytes and around intramyocardial branches of the coronary arteries. The long-term low-dosage administration of an inhibitor of the NO synthase such as L-NAME causes myocyte hypertrophy and early interstitial and perivascular fibrosis without important quantitative changes in microcirculation.