Hesperidin Ameliorates Anxiety-Depressive-Like Behavior in 6-OHDA Model of Parkinson's Disease by Regulating Striatal Cytokine and Neurotrophic Factors Levels and Dopaminergic Innervation Loss in the Striatum of Mice
MOLECULAR NEUROBIOLOGY
Authors: Antunes, Michelle S.; Souza, Leandro Cattelan; Lobo Ladd, Fernando Vagner; Barbosa Lobo Ladd, Aliny Antunes; Moreira, Amanda Lopez; Bortolotto, Vandreza Cardoso; Poetini Silva, Marcia Rosula; Araujo, Stifani Machado; Prigol, Marina; Nogueira, Cristina Wayne; Boeira, Silvana Peterini
Abstract
The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p < 0.05). It also attenuated the striatal levels of proinflammatory cytokines tumor necrosis factor-alpha, interferon-gamma, interleukin-1 beta, interleukin-2, and interleukin-6 and increased the levels of neurotrophic factors, including neurotrophin-3, brain-derived neurotrophic factor, and nerve growth factor in the striatum of 6-OHDA mice (p < 0.05). Hesperidin treatment was also capable to increase striatal levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid and protects against the impairment of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (p < 0.05). In conclusion, this study indicated that hesperidin exerts anxiolytic-like and antidepressant-like effect against 6-OHDA-induced neurotoxicity through the modulation of cytokine production, neurotrophic factors levels, and dopaminergic innervation in the striatum.
A Preliminary Description of the Sleep-Related Neural Systems in the Brain of the Blue Wildebeest,Connochaetes taurinus
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
Authors: Malungo, Illke B.; Gravett, Nadine; Bhagwandin, Adhil; Davimes, Joshua G.; Manger, Paul R.
Abstract
The current study provides a detailed qualitative description of the organization of the cholinergic, catecholaminergic, serotonergic, orexinergic, and GABAergic sleep-related systems in the brain of the blue wildebeest (Connocheates taurinus), along with a quantitative analysis of the pontine cholinergic and noradrenergic neurons, and the hypothalamic orexinergic neurons. The aim of this study was to compare the nuclear organization of these systems to other mammalian species and specifically that reported for other Cetartiodactyla. In the brain of the blue wildebeest, from the basal forebrain to the pons, the nuclear organization of the cholinergic, catecholaminergic, serotonergic, and orexinergic systems, for the most part, showed a corresponding nuclear organization to that reported in other mammals and more specifically the Cetartiodactyla. Furthermore, the description and distribution of the GABAergic system, which was examined through immunostaining for the calcium binding proteins calbindin, calretinin, and parvalbumin, was also similar to that seen in other mammals. These findings indicate that sleep in the blue wildebeest is likely to show typically mammalian features in terms of the global brain activity of the generally recognized sleep states of mammals, but Cetartiodactyl-specific features of the orexinergic system may act to lower overall daily total sleep time in relation to similar sized non-Cetartiodactyl mammals. Anat Rec, 2019. (c) 2019 American Association for Anatomy Anat Rec, 303:1977-1997, 2020. (c) 2019 American Association for Anatomy