Neuroscience
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The medial preoptic area (mPOA) participates in the temperature and cardiovascular control. The mPOA receives inputs from limbic structures and sends projections to hypothalamus and brainstem. Moreover, stress elicits pronounced neuronal activation in mPOA, suggesting its involvement in central neural pathway mediating stress responses. ⋯ In addition, pretreatment of mPOA with CoCl2 increased RS-evoked tachycardic and hyperthermic responses evoked by RS when compared with aCSF-treated animals, without affecting the RS-evoked pressor response and the fall in Ttail. In summary, our results suggest that mPOA exerts a tonic inhibitory influence on the sympathetic cardiac tone under both rest and stress conditions, modulating negatively the sympathetic component of baroreflex. Results also confirm the mPOA involvement in the control of body temperature because its inhibition was followed by a sustained increase in body temperature and vasoconstriction in the tail artery territory.
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Patients with Parkinson's disease (PD), and especially those with freezing of gait (FOG), are known to experience impairments in gait rhythmicity, symmetry, and bilateral coordination between both legs. In the current study, we investigated whether deficits in perception of gait speed between limbs were more pronounced in freezers than in non-freezers and could explain some of these gait impairments. We also assessed cognitive ability and proprioception. ⋯ Greater step length and limb excursions were associated with better perception, whereas more variable gait was associated with more impaired perception. The results confirm the hypothesis that freezers have impaired perception of locomotor asymmetry. While proprioceptive and cognitive ability did not explain these findings, the possible causal link with the occurrence of FOG needs further corroboration.
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Stress during early development produces lasting effects on psychopathological outcomes. We analysed the impact of prior intermittent, physical stress (IPS) during early adolescence (PD 22-33) on anxiety-like behaviour of female rats in adulthood. After behavioural testing, we used immunohistochemistry for the 5-HT transporter (SERT) to evaluate 5-HT innervation profiles in the medial prefrontal cortex (mPFC) and ventral hippocampus (VH). ⋯ Selective stress-induced increases in the density of SERT-ir positive fibres were found in the infralimbic (IL) subregion of the mPFC but not in the cingulate or prelimbic (PL) subregions. IPS in early adolescence did not affect 5-HT innervation profiles in any sub-fields of the VH. Our findings confirm and extend on earlier evidence that stress during early adolescence promotes the emergence of an anxious phenotype and provide novel evidence that these effects are associated with increased 5-HT innervation of the IL mPFC.
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Both insulin signaling disruption and Ca2+ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca2+-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca2+-dependent AHP. ⋯ Results indicate that insulin reduced Ca2+ transients, which appears to have involved a reduction in ryanodine receptor function. Together, these results suggest insulin regulates pathways that control intracellular Ca2+ which may reduce the AHP and improve memory. This may be one mechanism contributing to improved memory recall in response to intranasal insulin therapy in the clinic.
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PTPN11 is associated with regulation of growth factor signaling pathways in neuronal cells. Using SH-SY5Y neuroblastoma cells, we showed that adeno-associated virus (AAV)-mediated PTPN11 upregulation was associated with TrkB antagonism, reduced neuritogenesis and enhanced endoplasmic reticulum (ER) stress response leading to apoptotic changes. Genetic knock-down of PTPN11 on the other hand leads to increased TrkB phosphorylation in SH-SY5Y cells. ⋯ This study provides evidence of molecular interactions between PTPN11 and the TrkB receptor in SH-SY5Y cells. The results reinforce the role played by PTPN11 in regulating neurotrophin protective signaling in neuronal cells and highlight that PTPN11 dysregulation promotes apoptotic activation. Based on these findings we suggest that blocking PTPN11 could have potential beneficial effects to limit the progression of neuronal loss in neurodegenerative disorders.