Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice.

The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning. Using RasGEF1b deficient mice (RasGEF1b-cKO), we investigated the impact of this gene deletion in behavior, cognition, brain neurochemistry and microglia morphology. We showed that RasGEF1b-cKO mice display spontaneous hyperlocomotion and anhedonia. RasGEF1b-cKO mice also exhibited compulsive-like behavior that was restored after acute treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (5 mg/kg). A down-regulation of mRNA of dopamine receptor (Drd1, Drd2, Drd4 and Drd5) and serotonin receptor genes (5Htr1a, 5Htr1b and 5Htr1d) was observed in hippocampus of RasGEF1b-cKO mice. These mice also had reduction of Drd1 and Drd2 in prefrontal cortex and 5Htr1d in striatum. In addition, morphological alterations were observed in RasGEF1b deficient microglia along with decreased levels of hippocampal BDNF. We provided original evidence that the deletion of RasGEF1b leads to unique behavioral features, implicating this factor in CNS functioning.

Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.

Weight-drop model as a valuable tool to study potential neurobiological processes underlying behavioral and cognitive changes secondary to mild traumatic brain injury.

The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.

Morfologia e morfometria da cérvice uterina de cabras sem raça definida da microrregião de Teresina-Piauí / Morphology and morphometry of the uterine cervice of cross breed goat from micro region of Teresina-Piauí

A criação de caprinos está em ascensão mundial. No Brasil, esta prática tem contribuído bastante na economia, principalmente da região Meio Norte, onde o clima predominante, o semiárido, é favorável à criação destes animais. As cabras sem raça definida (SRD) podem apresentar alterações morfofisiológicas adaptativas para viverem neste ambiente específico. As adaptações podem ocasionar modificações que fogem ao padrão geralmente observado. Na análise macroscópica foram observados trinta úteros de cabras SRD quanto a topografia, morfometria e quantificação dos anéis cervicais uterinos. Das estruturas analisadas, observaram-se diferenças apenas quanto ao número de anéis, quando comparados com outros pequenos ruminantes. A estrutura histológica da cérvice foi analisada em microscopia de luz. Este órgão é composto predominatemente por tecido conjuntivo, apresentando pouco tecido muscular. A luz do colo uterino é revestida por um epitélio pseudoestratificado com células caliciformes. A mucosa endocervical apresenta dobras longitudinais e é repleta de glândulas secretoras de muco. As camadas musculares encontram-se dispostas de forma circular (interna), longitudinal (externa) e com algumas fibras transversais. Assim, as características anatômicas da cérvice uterina de cabras sem raça definida são importantes para uma melhor execução das técnicas de manejo reprodutivo, bem como para biologia destes animais.

Goat farming is steadily increasing worldwide. In Brazil this practice have contributed a lot in the economy, especially the Mid-North region, where the semi-arid prevailing climate is favorable to the creation of these animals. To live in this environment, the cross breed goat may have morpho-physiological adaptive changes, which may cause changes that are beyond the pattern usually observed. Thirty cross breed goat uterus were selected for topographic and morphometric analysis and quantification of uteri cervical rings. In analyzed structures, differences were observed only on the number of rings when compared with others small ruminants. The histological structure of the cervix was examined under light microscopy. This body is predominately composed of connective tissue with little muscle tissue. The light of the cervix is lined by a pseudostratified epithelium with goblet cells. The endocervical mucosa has longitudinal folds and is lined with mucus-secreting glands. Muscle layers are arranged circular (internal), longitudinal (external) and some transverse fibers. Thereby, the anatomical characteristics of the uterine cervix of cross breed goats are important both to the improvement of the reproductive management techniques as to the biology of this animal.