Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of Substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Activation of the mixed lineage kinase and c-Jun N-terminal kinase (JNK) has been reported in models of PD. Our focus was to discern whether distinct pathways were activated in cell-specific manner within the SNpc. We now demonstrate the selective phosphorylation of p38 MAP kinase within the dopaminergic neurons, whereas JNK activation occurs predominantly in the microglia. p38 activation results in downstream phosphorylation of p53 and increased p53 mediated transcription of Bax and Puma in the ventral midbrain. Treatment with p38 inhibitor, SB239063 protected primary dopaminergic neurons derived from human progenitor cells from MPP+ mediated cell death and prevented the downstream phosphorylation of p53 and its translocation to the nucleus in vivo, in the ventral midbrain. The increased staining of phosphorylated p38 in the surviving neurons of SNpc in human brain sections from patients with PD and in MPTP treated mice but not in the ventral tegmental area provides further evidence suggesting a role for p38 in the degeneration of dopaminergic neurons of SNpc. We thus demonstrate the cell specific activation of MAP kinase pathways within the SNpc after MPTP treatment emphasizing the role of multiple signaling cascades in the pathogenesis and progression of the disease. Selective inhibitors of p38 may therefore, help preserve the surviving neurons in PD and slow down the disease progression

Regional variation in pig farmer awareness and actions regarding Japanese encephalitis in Nepal : implications for public health education

The objective was to explore regional variations in farmer awareness and actions towards Japanese Encephalitis (JE) in Nepal; the association of awareness and actions with farm and farmer variables; and the implications for public health education and extension services. Social factors such as literacy, gender, and cultural practices were associated with farmer attitudes, knowledge and practices for JE control. The low uptake of vaccine and lack of infrastructure or financial capacity to house pigs adequately suggest that farmer personal protection should be a priority for education. JE is a mosquito-borne zoonotic disease with pigs as the amplifying hosts

Comparative spatial dynamics of Japanese encephalitis and acute encephalitis syndrome in Nepal

Geographical patterns can provide important clues about disease etiology. Infectious diseases, such as Japanese Encephalitis (JE), are driven by ecological and social processes which result in heterogeneous distribution of disease risk. Pattern indices describing the amount of irrigated land edge density and the degree of landscape mixing for irrigated areas were positively associated with (JE) and acute encephalitis syndrome (AES) risk, while fragmented forest measured by the number of forest patches were negatively associated with AES and JE. These landscape variables highlight the importance of integrating healthy land management policies and disease prevention strategies in both rural and urban-fringe developing areas