Neuroscience
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Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. ⋯ No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system.
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An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. ⋯ We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.
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Amyotrophic lateral sclerosis (ALS) is an idiopathic and lethal neurodegenerative disease that currently has no effective treatment. A recent study found that the Notch signaling pathway was up-regulated in a TAR DNA-binding protein-43 (TDP-43) Drosophila model of ALS. Notch signaling acts as a master regulator in the central nervous system. ⋯ We found that the Notch pathway was activated in in vitro and in vivo models of ALS, and suppression of Notch activation with a Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) and Notch1 siRNA significantly reduced neuronal apoptotic signaling, as evidenced by the up-regulation of Bcl-2 as well as the down-regulation of Bax and cytochrome c. We also found that lithium and VPA suppressed the Notch activation associated with the superoxide dismutase-1 (SOD1) mutation, and the combination of lithium and VPA produced a more robust effect than either agent alone. Our findings indicate that the Notch pathway plays a critical role in ALS, and the neuroprotective effects of lithium and VPA against mutant SOD1-mediated neuronal damage are at least partially dependent on their suppression of Notch activation.
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The retina is a metabolically highly active tissue that is sensitive to pH changes. Blinding diseases of the retina are often characterized by degeneration of photoreceptor cells altering the acid-base homeostasis of the tissue microenvironment and by an accompanying inflammatory response. GPR4, GPR65 and GPR68 are G protein-coupled receptors that aid cells to sense and survive conditions of acidic pH and inflammatory cells express Gpr65 enhancing their viability. ⋯ We observed increased retinal expression of Gpr65, but not of Gpr4 and Gpr68, in mouse models of both inherited (rd10) and induced (light damage) retinal degeneration. Lack of GPR65 slightly accelerated photoreceptor degeneration in rd10 mice and resulted in a strong activation of microglia after light-injury. Since GPR65 was dispensable for normal retinal development, function and aging as evidenced by the evaluation of Gpr65(-/-) mice, our results indicate that the proton-sensing G protein-coupled receptor GPR65 may be involved in a mechanism that supports survival of photoreceptors in the degenerating retina.
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Schizophrenia patients treated with olanzapine, or other second-generation antipsychotics, frequently develop metabolic side-effects, such as glucose intolerance and increased adiposity. We previously observed that modeling these adverse effects in rodents also resulted in hippocampal shrinkage. Here, we investigated the impact of olanzapine treatment, and the beneficial influence of routine exercise, on the neurosecretion machinery of the hippocampus. ⋯ Syntaxin-1 depletion appeared more prominent in VGAT-positive terminals within the dentate gyrus, and in non-VGAT/VGLUT1-overlapping areas of CA3. The present findings suggest that chronic exposure to olanzapine may alter hippocampal connectivity, especially in inhibitory terminals within the dentate gyrus, and along the mossy fibers of CA3. Together with previous studies, we propose that exercise-based therapies might be beneficial for patients being treated with olanzapine.