Neuroscience
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We have shown that intravenous immunoglobulin (IVIG) contains anti-Aβ autoantibodies and IVIG could induce beta amyloid (Aβ) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Aβ efflux remains unclear. In this study, we used amyloid precursor protein (AβPP) transgenic mice to investigate if the IVIG could induce efflux of Aβ from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Aβ transporter in blood-CSF barrier (BCB); could mediate this clearance process. ⋯ In the mechanistic study, IVIG could induce Aβ efflux through the in vitro BCB membrane formed by cultured BCB epithelial cells. Both receptor-associated protein (RAP; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Aβ efflux. Should Aβ prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for AD by inducing efflux of Aβ from the brain through the LRP1 in the BCB.
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We tested the hypothesis that the angiotensinergic neurotransmission, specifically in the paraventricular nucleus of the hypothalamus (PVN), is involved in the cardiovascular modulation during acute restraint stress (RS) in rats. The intravenous pretreatment with the angiotensin AT1 receptor antagonist losartan (5mg/kg) inhibited the pressor response to RS, but did not affect the concomitant RS-evoked tachycardiac response. Because similar effects were observed after the PVN pretreatment with CoCl2, and considering the high density of angiotensin receptors reported in the PVN, we studied the effect of the pretreatment of the PVN with either losartan or the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the RS-evoked cardiovascular response. ⋯ When animals were pretreated with such doses of either losartan or lisinopril, the cardiovascular RS-evoked response was not affected, thus indicating that even if there were a complete leakage of the drug to the periphery, it would not affect the cardiovascular response to RS. This observation favors the idea that the effect of the intravenous injection of 5mg/kg of losartan on the RS-related cardiovascular response would be explained by an action across the blood-brain barrier, possibly in the PVN. In conclusion, the results suggest that an angiotensinergic neurotransmission in the PVN acting on AT1-receptors modulates the vascular component of the RS-evoked cardiovascular response.
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Deficient reelin signaling leads to characteristic layering malformations in the cerebral cortex and causes polarity defects of cortical neurons. Since the discovery of reelin much has been learned about the molecular mechanisms that underlie the characteristic defects of layering defects in the reeler mutant. More recent studies provided insights in the crosstalk between reelin signaling and molecular pathways that control polarity development of radially migrating neurons. The present review summarizes and discusses recent findings on the role of reelin in modulating polarization and process orientation of neurons in the neocortex and hippocampus.
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Proper development of the auditory cortex depends on early acoustic experience that modulates the balance between excitatory and inhibitory (E/I) circuits. In the present social and occupational environment exposure to chronic loud sound in the form of occupational or recreational noise, is becoming inevitable. This could especially disrupt the functional auditory cortex development leading to altered processing of complex sound and hearing impairment. ⋯ Expressions of markers of synaptogenesis, synaptic stability and plasticity i.e., synaptophysin, PSD-95 and gephyrin were reduced with noise but increased with music exposure. Thus our results showed differential effects of prenatal chronic loud noise and music exposures on the E/I balance and synaptic function and stability in the developing auditory cortex. Loud music exposure showed an overall enrichment effect whereas loud noise-induced significant alterations in E/I balance could later impact the auditory function and associated cognitive behavior.
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Traumatic spinal cord injury induces a long-standing inflammatory response in the spinal cord tissue, leading to a progressive apoptotic death of spinal cord neurons and glial cells. We have recently demonstrated that immediate treatment with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC) attenuates neuroinflammation, induces axonal sprouting, and reduces the death of motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The objective of the current study was to investigate the effects of long-term antioxidant treatment on the survival of descending rubrospinal neurons after spinal cord injury in rats. ⋯ Treatment also decreased the expression of BAX, caspase 3, OX42 and ED1 after 2 weeks. After 8 weeks, treatment decreased immunoreactivity for OX42, whereas it was increased for 5HT. In conclusion, this study provides further insight in the effects of treatment with NAC and ALC on descending pathways, as well as short- and long-term effects on the spinal cord trauma zone.