ABSTRACT
Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes. Our goal was to design and test the neurotherapeutic potential of a forefront nanoparticle-based technology composed of albumin/PLGA nanosystems loaded with dopamine (ALNP-DA) in 6-OHDA PD mice model. ALNP-DA effectively crossed the BBB, replenishing dopamine at the nigrostriatal pathway, resulting in significant motor symptom improvement when compared to Lesioned and L-DOPA groups. Notably, ALNP-DA (20 mg/animal dose) additionally up-regulated and restored motor coordination, balance, and sensorimotor performance to non-lesioned (Sham) animal level. Overall, ALNPs represent an innovative, non-invasive nano-therapeutical strategy for PD, considering its efficacy to circumvent the BBB and ultimately deliver the drug of interest to the brain.
Subject(s)
Blood-Brain Barrier/metabolism , Dopamine/administration & dosage , Dopamine/pharmacokinetics , Drug Delivery Systems , Nanoparticles/administration & dosage , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/metabolism , Animals , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Dopaminergic Neurons/drug effects , Humans , Male , Mice , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Nanotechnology , Oxidopamine/toxicity , Parkinsonian Disorders/chemically induced , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/chemistryABSTRACT
Parkinson's disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp Parachartergus fraternus and evaluated its neuroprotective activity in the murine model of PD. For this purpose, the venom was filtered and separated through HPLC; fractions were analyzed through mass spectrometry and the active fraction was identified as a novel peptide, called Fraternine. We performed two behavioral tests to evaluate motor discoordination, as well as an apomorphine-induced rotation test. We also conducted an immunohistochemical assay to assess protection in TH+ neurons in the Substantia Nigra (SN) region. Group treated with 10 µg/animal of Fraternine remained longer in the rotarod compared to the lesioned group. In the apomorphine test, Fraternine decreased the number of rotations between treatments. This dose also inhibited dopaminergic neuronal loss, as indicated by immunohistochemical analysis. This study identified a novel peptide able to prevent the death of dopaminergic neurons of the SN and recover motor deficit in a 6-OHDA-induced murine model of PD.
Subject(s)
Behavior, Animal/drug effects , Dopaminergic Neurons/drug effects , Motor Activity/drug effects , Neuroprotective Agents/pharmacology , Parkinsonian Disorders/drug therapy , Peptides/pharmacology , Substantia Nigra/drug effects , Wasp Venoms/chemistry , Animals , Cell Death/drug effects , Disease Models, Animal , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Female , Male , Mice , Nerve Degeneration , Neuroprotective Agents/isolation & purification , Oxidopamine , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/physiopathology , Peptides/isolation & purification , Rotarod Performance Test , Substantia Nigra/metabolism , Substantia Nigra/physiopathology , WaspsABSTRACT
Studies on avian haemosporidia are on the rise, but we still lack a basic understanding of how ecological and evolutionary factors mold the distributions of haemosporidia among species in the same bird community. We studied the structure and organization of a local avian haemosporidian assemblage (genera Plasmodium and Haemoproteus) in the Cerrado biome of Central Brazil for 5 years. We obtained 790 blood samples from 54 bird species of which 166 (21%) were infected with haemosporidians based on molecular diagnostics. Partial sequences of the parasite cytochrome b gene revealed 18 differentiated avian haemosporidian lineages. We also analysed the relationship of life-history traits (i.e., nesting height, migration status, nest type, sociality, body mass, and embryo development period) of the 14 most abundant bird species with the prevalence of avian haemosporidia. It was found that host species that bred socially presented a higher prevalence of Haemoproteus (Parahaemoproteus) than bird species that bred in pairs. Thus, aspects of host behaviour could be responsible for differential exposure to vectors. The assemblage of avian haemosporidia studied here also confirms a pattern that is emerging in recent studies using molecular markers to identify avian haemosporidians, namely that many lineages are host generalists.
