Neuroscience
-
Resveratrol pretreatment has been shown to provide neuroprotection in models of cerebral ischemia. This phenomenon, commonly termed preconditioning, promotes ischemic tolerance and may involve mild activation of endoplasmic reticulum stress pathways in the affected tissue. Systemic injection of resveratrol (2 x 10(-3), 2 x 10(-4), 1 x 10(-4) mg/kg) 30 min prior to a 4 h period of right middle cerebral artery occlusion significantly reduced infarct area in the insular region of rat prefrontal cortex. ⋯ The calcium-sensitive chaperone heat shock protein 70 and the cysteine protease m calpain did not respond to resveratrol pretreatment. However, a significant induction of heat shock protein 70 was observed in the contralateral cortex of resveratrol pretreated rats following 4 h of right middle cerebral artery occlusion. These data suggest that resveratrol preconditioning promotes ischemic tolerance in the short term, in part via effects mediated through activation of estrogen and NMDA receptors, as well as through mild activation of cellular stress proteins.
-
It is poorly understood if and how pain may modify the effect of opioids on neural systems that contribute to reward and addictive behavior. We hypothesized that the activation of ascending dopaminergic and serotonergic nuclei by morphine is modified by the presence of noxious stimulation. Immunohistochemical double-labeling technique with Fos was used to examine if an intraplantar formalin injection, an acute noxious input, changed the effect of morphine on dopaminergic neurons of the ventral tegmental area (VTA), and serotonergic neurons of the dorsal raphe nucleus (DR). ⋯ Therefore, morphine's activation of the VTA, which is associated with motivated behavior and reward seeking, appears similar in the context of pain. However, activation of the ascending serotonin system, which influences mood and has the capacity to modify reward pathways, appears different. In addition, these findings reveal interactions between nociceptive signaling and opioids that contrasts with the notion that opioids simply block access of nociceptive signaling to supraspinal structures.
-
Endogenous opioid peptides are involved in prolactin release during lactation, in part by decreasing tuberoinfundibular dopaminergic (TIDA) neuronal activity. Both mu (mu) and kappa (kappa) opioid receptors have a role in the suckling-induced prolactin rise after 4-5 h up deprivation. The aim of this study was to investigate effects of mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), and kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on prolactin secretion and TIDA neuronal activity in lactating rats after 18 h pup deprivation. ⋯ These data support involvement of endogenous opioidergic systems in the suckling-induced prolactin rise after a prolonged (18 h) period of pup deprivation, as well as the shorter (4 h) pup deprivation period previously reported. Suppression of TIDA neuronal activity likely played a part in mu opioid receptor input to the suckling-induced prolactin rise after both 4 h and 18 h separation, whereas non-dopaminergic input was implicated with kappa opioid receptors after 18 h pup deprivation. Increased mu and kappa opioid receptors gene expression in the mediobasal hypothalamus may contribute to reduced effectiveness of opioid receptor antagonists to block suckling-induced prolactin release after 18 h pup deprivation.
-
Rats receiving a complete spinal cord transection (ST) at a neonatal stage spontaneously can recover significant stepping ability, whereas minimal recovery is attained in rats transected as adults. In addition, neonatally spinal cord transected rats trained to step more readily improve their locomotor ability. We hypothesized that recovery of stepping in rats receiving a complete spinal cord transection at postnatal day 5 (P5) is attributable to changes in the lumbosacral neural circuitry and not to regeneration of axons across the lesion. ⋯ Retrograde labeling transsynaptically via injection of pseudorabies virus (Bartha) into the soleus and tibialis anterior muscles showed no labeling in the same brain nuclei. Furthermore, re-transection of the spinal cord at or rostral to the original transection did not affect stepping ability. Combined, these results clearly indicate that there was no regeneration across the lesion after a complete spinal cord transection in neonatal rats and suggest that this is an important model to understand the higher level of locomotor recovery in rats attributable to lumbosacral mechanisms after receiving a complete ST at a neonatal compared to an adult stage.
-
The mechanisms underlying diabetic encephalopathy, are largely unknown. Here, we examined whether docosahexaenoic acid (DHA) and lutein could attenuate the oxidative changes of the diabetic cerebral cortex. The levels of malondialdehyde (MDA) were significantly increased and glutathione (GSH) and glutathione peroxidase activity (GPx) were decreased in diabetic rats. ⋯ The latter demonstrated extensive overlap with the 4-HNE staining in the cortex from diabetic rats. Our findings demonstrate a clear participation of glucose-induced oxidative stress in the diabetic encephalopathy, and that the cells suffering oxidative stress are neurons. Lowering oxidative stress through the administration of different antioxidants may be beneficial for the central nervous tissue in diabetes.