Neuroscience
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Fibronectin type III domain containing 5 (Fndc5) has already been distinguished to be involved in neural differentiation. However, cellular events of Fndc5 function are still ambiguous in the nervous system. One approach to shed light on duty of this protein in the nervous system is to find its cross-talks with various signaling pathways with defined characteristics and roles. ⋯ Furthermore, inhibition of this pathway by PD0325901 dramatically reduced Fndc5 mRNA level, while activating the pathway up-regulated Fndc5 transcription. In addition, it has been proven that ERK1/2 modulation via RA has more significant controlling effect on Fndc5 promoter rather than bFGF. This led us to conclude that RA enhances Fndc5 expression through a non-genomic pathway via the ERK signaling pathway.
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Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2h vs. 24h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2h vs. 24h after PD. ⋯ We also found for the first time a significant increase 2h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal.
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Somatostatin is a 14-28 amino acid peptide that is located not only in the gastrointestinal system but also in multiple sites of the human brain. The inhibitory effect of somatostatin on the growth hormone (GH) secretion of the pituitary gland is a well-established phenomenon. There is a general consensus that somatostatin is released into the hypophysial portal blood and modulates GH secretion by hormonal action. ⋯ The morphology and the abundance of somatostatin to GHRH juxtapositions indicate that these associations are functional synapses, and they represent, at least partially, the morphological substrate of the somatostatin-influenced GHRH secretion. Thus, in addition to influencing the GH secretion directly via the hypophysial portal system, somatostatin may also modulate GH release from the anterior pituitary by regulating the hypothalamic GHRH secretion via direct contacts. The rare GHRH to somatostatin juxtapositions indicate that the negative feedback effect of GH targets the somatostatinergic system directly and not via the GHRH system.
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We investigated the role of the autonomic nervous system to cardiovascular responses to obstructive apnea in awake, unrestrained rats, and measured expression of Fos induced by apnea in the brainstem. We implanted a tracheal balloon contained in a rigid tube to allow the induction of apnea without inducing pain in the trachea. During bouts of 15s of apnea, heart rate fell from 371±8 to 161±11bpm (mean±SEM, n=15, p<0.01) and arterial pressure increased from 115±2 to 131±4mmHg (p<0.01). ⋯ Apnea induced Fos expression in several brainstem areas involved in cardiorespiratory control such as the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and pons. Ligation of the carotid body artery reduced apnea-induced bradycardia, blocked heart rate responses to i.v. injection of cyanide, reduced Fos expression in the caudal NTS, and increased Fos expression in the rostral VLM. In conclusion, apnea activates neurons in regions that process signals from baroreceptors, chemoreceptors, pulmonary receptors, and regions responsible for autonomic and respiratory activity both in the presence and absence of carotid chemoreceptors.
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Recent studies have demonstrated that inflammatory and immune mechanisms play important roles in the progression of chronic cerebral hypoperfusion (CCH)-induced white matter lesions (WMLs). As an endogenous neuromodulator in the brain, the extracellular levels of adenosine represent a critical endogenous mechanism for the regulation of immune and inflammatory responses. Ecto-5'-nucleotidase (CD73), which dephosphorylates AMP to adenosine, is considered to catalyze the rate-limiting step in the generation of extracellular adenosine. ⋯ More reactive astrocytes and microglia were observed in the corpus callosum in CD73-KO mice. CD73 deficiency significantly increased the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the BCAS model of CCH. These findings suggest that CD73 plays a protective role in the development of CCH-induced WMLs and cognitive impairment via the regulation of glial cell activation and proinflammatory cytokine expression.