The effects of corticotropin-releasing factor on motor learning.

Corticotropin-releasing factor (CRF) is mainly secreted from the hypothalamic paraventricular nuclei and plays a crucial role in stress-related responses. Recent studies have reported that CRF is a neuromodulator in the central nervous system. In the cerebellum, CRF is essential for the induction of long-term depression (LTD) at the parallel fiber-Purkinje cell synapses. Given that LTD is thought to be one of the fundamental mechanisms of motor learning, CRF may affect motor learning. However, the role of CRF in motor learning in vivo remains unclear. In this study, we aimed to examine the role of CRF in motor learning. This was achieved through a series of behavioral experiments involving the in vivo administration of CRF and its antagonists. Rats injected with CRF directly into the cerebellum exhibited superior performance on the rotarod test, especially during initial training phases, compared to control subjects. Conversely, rats receiving a CRF receptor antagonist demonstrated reduced endurance on the rotating rod compared to controls. Notably, CRF mRNA expression levels in the cerebellum did not show significant variance between the CRF-injected and control groups. These findings imply a critical role of endogenous CRF in cerebellar motor learning and suggest that exogenous CRF can augment this process. (199 words).

Participation of the nucleus accumbens dopaminergic system in the antidepressant-like actions of a diet rich in omega-3 polyunsaturated fatty acids.

The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.

Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice.

Patients and rodents with cerebellar damage display ataxic gaits characterized by impaired coordination of limb movements. Here, gait ataxia in mice with a null mutation of the gene for the cerebellin 1 precursor protein (cbln1-null mice) was investigated by kinematic analysis of hindlimb movements during locomotion. The Cbln1 protein is predominately produced and secreted from cerebellar granule cells. The cerebellum of cbln1-null mice is characterized by an 80% reduction in the number of parallel fiber-Purkinje cell synapses compared with wild-type mice. Our analyses identified prominent differences in the temporal parameters of locomotion between cbln1-null and wild-type mice. The cbln1-null mice displayed abnormal hindlimb movements that were characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles and knees. When recombinant Cbln1 protein was injected into the cerebellum of cbln1-null mice, the step cycle and stance phase durations increased toward those of wild-type mice, and the angular excursions of the knee during a cycle period showed a much closer agreement with those of wild-type mice. These findings suggest that dysfunction of the parallel fiber-Purkinje cell synapses might underlie the impairment of hindlimb movements during locomotion in cbln1-null mice.

Preparation of Bioadhesive Phosphorescent Particles and Their Use as Markers for Video-oculography of Mice.

OBJECTIVE: To develop a bioadhesive phosphorescent particle that can be used as a marker in video-oculography to assess eye movements in the dark without drug treatment. METHODS: The marker was prepared by spray-coating a Sr4Al14O25: Eu2+, Dy3+ phosphor with a carboxyvinyl polymer. The morphologic, luminescent and adhesive properties were assessed. The dynamic properties of VOR measured by the marker were compared with those obtained by tracking the pupil under miotic treatment. RESULTS: Non-aggregated and non-fused particles having diameters of about 5µm could be prepared by polymeric coating of the phosphor, resulting in particles small enough not to restrict eye movement. Although the phosphorescent of the particles decreased with increasing thickness of the coating layer, the coated particles were detectable in the dark for at least 60 min. The thicker the coating layer was, the higher the adhesiveness of the particles obtained. The particles having the thickest coating layer were retained on the corneal surface during VOR measurement and thus performed well as a marker in video-oculography. The dynamic properties of VOR measured by the marker were essentially identical to those obtained by tracking the pupil under miotic treatment. CONCLUSION: Our marker will contribute to understanding the mechanisms underlying motor learning.

Characteristics of gait ataxia in δ2 glutamate receptor mutant mice, ho15J.

The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.

Definição de níveis aceitáveis baseados no risco para hidrocarbonetos no Município de Porto Alegre segundo a metodologia RBCA / Definition of risk-based screening levels to hydrocarbons in Porto Alegre municipality according to the RBCA methodology

O presente estudo definiu valores de NABR (Níveis Aceitáveis Baseados no Risco) para hidrocarbonetos no Município de Porto Alegre, de acordo a metodologia RBCA, adotando-se dados hidrogeológicos dos compartimentos Embasamento Cristalino alterado e Depósitos Sedimentares Quaternários. Os parâmetros de exposição adequados à população do município, bem como dados de toxicidade dos compostos selecionados, foram definidos a partir de fontes bibliográficas e bancos toxicológicos disponíveis. As tabelas de referência geradas são, em geral, mais restritivas para o Embasamento Cristalino em relação aos Depósitos Sedimentares. Comparados às tabelas de referência da Cetesb, os valores correspondentes a Porto Alegre são inferiores, resultando na necessidade de investigações ambientais mais detalhadas em áreas impactadas por hidrocarbonetos.

This study defined RBSL (Risk Based Screening Levels) values to hydrocarbons in Porto Alegre, Southern Brazil. The values were obtained through the RBCA methodology, using hydrogeological data from the Crystalline Altered Basement and the Quaternary Sedimentary Deposits. The exposure parameters appropriate to the urban population, as well as toxicity data of selected compounds, were obtained from bibliographical sources and toxicological databases. The reference tables demonstrated that the Crystalline Altered Basement values, in general, are more restrictive than those from the Quaternary Sedimentary Deposits. In comparison to Cetesb's reference tables, the values in Porto Alegre are lower, resulting in the need of more detailed environmental investigations in hydrocarbons polluted areas.