Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

BACKGROUND: Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. METHODS: The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. RESULTS: We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. CONCLUSIONS: Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia-induced neuroinflammation. Importantly, our results also open promising new perspectives for the therapeutic use of H1R antagonists to treat or ameliorate neurodegenerative processes.

High-Precision Optical Fiber-Based Lickometer.

Quantifying and analyzing licking behavior can offer valuable insights into fundamental neurobiological mechanisms controlling animal consummatory behaviors. Lickometers are typically based on electrical properties, a strategy that comes with limitations, including susceptibility to electrical interference and generation of electrical disturbances in electrophysiological measurements. While optical lickometers offer an alternative method to measure licks and quantify fluid intake in animals, they are prone to false readings and susceptibility to outside light sources. To overcome this problem, we propose a low-cost open-source lickometer that combines a restricted infrared beam defined by optical fibers, with a poke design that allows easy access to the tongue while limiting access of other body parts and external light sources. This device also includes features for detecting nose pokes and presenting visual cues during behavioral tasks. We provide validation experiments that demonstrate the optical lickometer's reliability, high-sensitivity and precision, and its application in a behavioral task, showcasing the potential of this tool to study lick microstructure in combination with other techniques, such as imaging of neural activity, in freely moving mice.

Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson's disease.

Retinoic acid (RA) plays an important role in the commitment, maturation and survival of neural cells. Recently, RA was pointed as a therapeutic option for some neurodegenerative diseases, including Parkinson's disease (PD). The administration of RA has been defying, and in this sense we have previously developed novel RA-loaded polymeric nanoparticles (RA-NPs) that ensure the efficient intracellular transport and controlled release of RA. Herein, we show that nanoformulation as an efficient neuroprotective effect on dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mouse model for PD. The results showed that the RA-NPs administration induced a significant reduction of DA neuron loss in the substantia nigra (SN) as well as their neuronal fiber/axonal innervations in the striatum. Furthermore, we observed an increase in the expression levels of the transcription factors Pitx3 and Nurr1 induced by RA-NPs, showing its supportive effect on the development and functional maintenance of DA neurons in PD. This is the first study showing that RA-NPs can be an innovative strategy to halt the progression of PD pathogenesis, suggesting that this nanoformulation could be of particular interest for the development of new approaches for PD therapeutics.

Avaliação da qualidade sanitária dos rótulos de alimentos embalados de origem animal / Health quality assessment of labels from packed food of animal origin

Neste estudo avlia-se a qualidade das informações e dos rótulos de alimentos embalados, de origem animal, importante instrumento de informação ao consumidor e da segurança sanitária e alimentar. Este é um estudo descritivo, no qual as unidades de observação foram os rótulos de alimentos de origem animal comercializados em supermercados das cidades de Barreiras e Salvador (BA). Foram analisados rótulos de ovos, mel, frango congelado, linguiça calabresa, iogurte e leite líquido de diversas marcas. As categorias analíticas foram: tipo de alimento, identificação do produtor, lote, inscrição Indústria Brasileira, registro no Ministério da Agricultura, validade, data de fabricação/envase, carimbo do serviço de inspeção, informações nutricionais e ingredientes, instruções sobre armazenamento e conservação, preparo ou uso, aderência do rótulo, legibilidade, visibilidade, coerência e clareza. Verificou-se que a maioria dos rótulos atendia a legislação em vigor. Inconformidades encontradas foram falta do número de lote e visibilidade das informações. Alimentos com pior qualidade da rotulagem foram ovos, mel e linguiça calabresa. Um maior controle sanitário das informações contidas nos rótulos de alimentos poderá tornar o consumidor mais consciente de seus direitos.