► Trans fat (TF) consumption can modify the neuronal plasticity causing motor diseases. ► TF-fed rats showed movement disorders, which was intensified by exercise. ► TF and lard decreased catalase ...activity, which was increased by exercise in TF group. ► Exercise increased striatal Na
+K
+-ATPase activity of lard and soybean-fed rats. ► TF inhibited benefits of exercise indicating its critical role in brain neurochemistry.
The influence of
trans fatty acids (FA) on development of orofacial dyskinesia (OD) and locomotor activity was evaluated. Rats were fed with diets enriched with 20% soybean oil (SO;
n
−
6 FA), lard (L; saturated FA) or hydrogenated vegetable fat (HVF;
trans FA) for 60 weeks. In the last 12 weeks each group was subdivided into sedentary and exercised (swimming). Brains of HVF and L-fed rats incorporated 0.33% and 0.20% of
trans FA, respectively, while SO-fed group showed no incorporation of
trans FA. HVF increased OD, while exercise exacerbated this in L and HVF-fed rats. HVF and L reduced locomotor activity, and exercise did not modify. Striatal catalase activity was reduced by L and HVF, but exercise increased its activity in the HVF-fed group. Na
+K
+-ATPase activity was not modified by dietary FA, however it was increased by exercise in striatum of SO and L-fed rats. We hypothesized that movement disorders elicited by HVF and less by L could be related to increased dopamine levels in striatum, which have been related to chronic
trans FA intake. Exercise increased OD possibly by increase of brain dopamine levels, which generates pro-oxidant metabolites. Thus, a long-term intake of
trans FA caused a small but significant brain incorporation of
trans FA, which favored development of movement disorders. Exercise worsened behavioral outcomes of HVF and L-fed rats and increased Na
+K
+-ATPase activity of L and SO-fed rats, indicating its benefits. HVF blunted beneficial effects of exercise, indicating a critical role of
trans FA in brain neurochemistry.
The c‐kit proto‐oncogene plays a dual role in the control of male fertility in mice through two alternative gene products: (1) c‐kit the transmembrane tyrosine kinase receptor for stem cell factor ...(SCF), which is expressed and functional in differentiating spermatogonia of the postnatal testis, in which c‐kit is essential for pre‐meiotic proliferation; and (2) tr‐kit, an intracellular protein which is specifically accumulated during spermiogenesis through the use of an alternative intronic promoter, and which is able to trigger mouse egg activation when microinjected into the cytoplasm of metaphase II arrested oocytes. Here, we summarize the most recent findings about the molecular pathways through which c‐kit regulates cell cycle progression in mitotic germ cells, and those through which sperm‐derived tr‐kit triggers parthenogenetic completion of meiosis II and pronuclear formation in microinjected mouse eggs.
Deposition of amphiphilic porphyrin derivatives occurs spontaneously on silanised glass surfaces, in a controlled fashion. The resulting porphyrin films show appreciable fluorescence emission. This ...emission can be effectively quenched by immersion of the slides into a diluted solution of Hg2+ (μM concentration). The initial intensity can be restored by washings with a solution of N,N,N′,N′-tetrakis(2-pyridilmethyl)ethylenediammine with no loss of efficiency. A remarkable selectivity is featured toward the detection of Hg2+ over Cu2+, Cd2+, Pb2+ and Zn2+ counterparts. This protocol can be extended to a flow-through apparatus. The presented results are of importance for the achievement of a solid-state chemosensor for mercuric ions, at micromolar concentration, in water.
We have recently developed a novel cell-based therapy consisting of autologous adult Regenerative Macrophages (REMaST®) for nervous tissue regeneration. Strong preclinical evidence has shown the ...effect of REMaST® on nerve growth and spinal cord injury (SCI) healing. Multiple administrations of REMaST®, starting from the subacute phase following severe (complete) compressive-contusive SCI, improved motor recovery and rewired the SCI hostile microenvironment, reducing the fibrotic scar, increasing vasculature and tissue oxygenation and dampening the chronic inflammation.
We now developed the GMP protocol to generate human REMaST® for clinical use. In this context, we developed quality controls (QCs) to define REMaST® quality attributes characterizing the safety (proliferation, genomic alteration), identity (gene and protein expression), and potency of the drug substance. Based on the major mechanisms of action observed in preclinical studies, we developed ad hoc potency/efficacy QCs to assess the neuroprotective (neurite outgrowth, neural cell survival in condition of oxygen and glucose deprivation), chemotactic (SDF-1), and immunomodulatory properties (skewing of M1 polarization).
We are further optimizing human REMaST® production using a close loop system enabling robust large-scale manufacturing of the drug product for clinical use.
► Orofacial dyskinesia (OD) and catalepsy were induced by reserpine and haloperidol. ► Pecan shell aqueous extract (AE) prevented and reversed OD. ► But only prevented the catalepsy induced by both ...animal models. ► Our results indicate the similarity between the two animal models. ► And show that the prevention of extrapyramidal disorder is better than its reversal.
Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed.
Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant.
When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal.
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