Neuroscience
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Comparative Study
Ventral tegmental area neurons are either excited or inhibited by cocaine's actions in the peripheral nervous system.
Cocaine's multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via its peripheral actions. ⋯ Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened and the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons before its well-known direct actions in the brain.
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We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric β-amyloid (Aβ(1-42)) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aβ clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aβ. ⋯ In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aβ peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aβ may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.
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The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. ⋯ Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of dark rearing and light exposure.
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Receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within the CNS and whether these receptors exist within the nucleus of the solitary tract (NTS), and their possible role in the regulation of arterial pressure (AP) is unknown. Experiments were done in the rat to: (1) map the distribution of STC-1 receptors throughout NTS using in situ ligand binding that uses a stanniocalcin-alkaline phosphatase (STC-AP) fusion protein; (2) determine whether protein and gene expression for STC-1 exists within NTS using immunohistochemistry, Western blot and real time qPCR; (3) determine the effect of microinjection of STC-1 into NTS on AP and the baroreflex. Cells exhibiting STC-1 binding sites were found mainly within the caudal medial (Sm), gelantinous and commissural subnuclei of NTS. ⋯ Additionally, injection of STC-1 into Sm potentiated the AP responses to electrical stimulation of the ipsilateral aortic depressor nerve. Finally, bilateral injection of STC-1 primary antiserum (1:1000; 100 nl) into Sm elicited a long lasting increase in AP, whereas microinjection of heat inactivated STC-1 antiserum did not alter AP. Taken together these data suggest that endogenous STC-1 signaling in NTS is involved in regulating the excitability of neurons that normally function as components of the baroreceptor reflex controlling AP.
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Many patients suffer from secondary muscle hyperalgesia after experiencing angina pectoris. In this study, we examined the role of the nucleus tractus solitarius (NTS) and glutamate receptors in modulating cardiac-evoked muscle hyperalgesia induced by pericardial capsaicin, which was monitored by recording electromyogram (EMG) activity from the spinotrapezius muscle in the anesthetized rat. Unilateral chemical lesioning of the commissural NTS with the neurotoxin ibotenic acid significantly depressed the cardiac-somatic reflex; the EMG responses decreased to 56.4 ± 6.9% of that of the controls (5 of 5). ⋯ When a combination of MK-801 and MCPG was administrated, the EMG response further decreased to 22.5 ± 13.2% (n=6) of that of the controls. However, administration of a non-NMDA receptor antagonist 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), at 2 and 5 nmol, had no effect on the EMG response. These results suggest that the NTS is involved in the facilitation of the cardiac-somatic reflex, and that the NMDA receptor and mGluRs play an important role in mediating this effect.