Neuroscience
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Alzheimer's disease (AD), the most common type of dementia, is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal loss in defined regions of the brain including the hippocampus and cortex. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) offers a safe and potentially effective tool for treating neurodegenerative disorders. However, the therapeutic effects of BM-MSCs on AD pathology remain unclear and their mechanisms at cellular and molecular levels still need to be addressed. ⋯ We also demonstrated amelioration of AD pathology by MSCs in vitro when these FAD neurons were co-cultured with MSCs, a paradigm that mimics the in vivo environment of post-transplantation of MSCs into damaged regions of brains. To overcome failed delivery of BDNF to the brain and to enhance MSCs releasing BDNF effect, we created BDNF-MSCs and found that MSCs protection was enhanced by BDNF-MSCs. This protection was abolished by BDNF-blocking peptides, suggesting that BDNF supply from BDNF-MSCs was enough to prevent AD pathology.
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Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson's disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. ⋯ We discuss neuroimaging studies that have identified key brain regions and modulatory mechanisms underlying placebo effects using well-established behavioral paradigms. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings.
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Glutamatergic synaptic activity entails a high energetic cost. During aging, a variety of neural metabolic changes have been reported that could compromise the capacity of neural circuits to maintain synaptic transmission during periods of reduced extracellular glucose. Indeed, a preferential compromise in evoked synaptic activity has been observed in hippocampal CA1 with age during exposure to low-glucose solutions. ⋯ However, orthodromic-evoked population spike amplitude and field excitatory post-synaptic potential (EPSP) slope were preferentially decreased in slices from aged rats during exposure to 1mM glucose-aCSF. Antidromic population spike amplitude was not differentially affected in slices from aged versus adult rats, however. These data suggest that synaptic efficacy is preferentially compromised with age under reduced glucose availability and, combined with a decreased capacity of the periphery to provide glucose to the central nervous system (CNS) during metabolically challenging conditions, could contribute to aging-related hippocampal dysfunction and cognitive decline.
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Acute bouts of aerobic physical exercise can modulate subsequent cognitive task performance and oscillatory brain activity measured with electroencephalography (EEG). Here, we investigated the sequencing of these modulations of perceptual and cognitive processes using scalp recorded EEG acquired during exercise. Twelve participants viewed pseudo-random sequences of frequent non-target stimuli (cars), infrequent distractors (obliquely oriented faces) and infrequent targets that required a simple detection response (obliquely oriented faces, where the angle was different than the infrequent distractors). ⋯ The P1 component evoked by infrequent targets also peaked earlier during low-intensity exercise compared to rest and high-intensity exercise. The P3a ERP component evoked by infrequent distractors measured at parietal electrodes peaked significantly earlier during both low- and high-intensity exercise when compared to rest. The modulation of the visual P1 and the later P3a components is consistent with the conclusion that exercise modulates multiple stages of neural information processing, ranging from early stage sensory processing (P1) to post-perceptual target categorization (P3a).
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Previous results from our laboratory showed that angiotensin II AT1 receptors (AT1-R) are involved in the neuroadaptative changes induced by amphetamine. The aim of the present work was to study functional and neurochemical responses to angiotensin II (ANG II) mediated by AT1-R activation in animals previously exposed to amphetamine. For this purpose male Wistar rats (250-320 g) were treated with amphetamine (2.5mg/kg/day intraperitoneal) or saline for 5 days and implanted with intracerebroventricular (i.c.v.) cannulae. Seven days after the last amphetamine administration the animals received ANG II (400 pmol) i.c.v. One group was tested in a free choice paradigm for sodium (2% NaCl) and water intake and sacrificed for Fos immunoreactivity (Fos-IR) determinations. In a second group of rats, urine and plasma samples were collected for electrolytes and plasma renin activity determination and then they were sacrificed for Fos-IR determination in Oxytocinergic neurons (Fos-OT-IR). ⋯ Repeated amphetamine exposure (a) prevented the increase in sodium intake and Fos-IR cells in caudate-putamen and accumbens nucleus induced by ANG II i.c.v. (b) potentiated urinary sodium excretion and Fos-OT-IR in hypothalamus and (c) increased the inhibitory response in plasma renin activity, in response to ANG II i.c.v. Our results indicate a possible functional desensitisation of AT1-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT1-R desensitisation allows to unmask the effects of ANG II i.c.v. mediated by oxytocin. We conclude that the long lasting changes in brain AT1-R functionality should be considered among the psychostimulant-induced neuroadaptations.