Transplantation of neural cells is a potential approach for the treatment of stroke, but the disruption of tissue architecture that accompanies stroke may limit the efficacy of transplantation. One strategy for enhancing the ability of transplants to restore brain structure and, thereby, function is to administer cells together with biomaterial scaffolding. We occluded the middle cerebral artery in adult rats and, 3 wks later, injected one of the following into the infarct cavity: (a) artificial cerebrospinal fluid, (b) Matrigel scaffolding, (c) human neuronal precursor cells, (d) scaffolding plus cells, or (e) cells cultured in and administered together with scaffolding. When tested up to 9 wks later, the latter group showed reduced infarct size, survival and neuronal differentiation of transplanted cells, and improved outcome on behavioral tests of sensorimotor and cognitive function. These results indicate that transplantation of human neural cells together with the scaffolding in which they are cultured has the potential to improve outcome from stroke, even when treatment is delayed for several weeks after the ischemic event.

One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.DOI: http://dx.doi.org/10.7554/eLife.09275.001

No abstract

The interaction of the basolateral amygdala and prelimbic cortex plays a crucial role in the reactivation of addiction memory.

Dopaminergic signaling in the basolateral amygdala (BLA) is important for drug-stimulus learning that triggers relapse to drug-seeking behavior. However, little is known about adaptive changes in this signaling pathway upon chronic morphine treatment. In this paper, we observed the influence of chronic morphine treatment on the effect of dopamine (DA) on the excitatory transmission in the pyramidal cells of BLA in slices with the whole-cell patch-clamp method. We also studied its mechanism and significance with pharmacological approaches combined with biochemical and behavioral techniques. The results showed that chronic morphine exposure switched the effect of DA on the excitatory synaptic transmission from inhibition to excitation; the chronic morphine-induced switching action on the effect of DA was due to its influence on D1 receptors; the site of the effect of chronic morphine treatment on D1 receptors was at presynaptic locus; chronic morphine treatment induced a significant increase in the amount of D1 receptor expression in the synaptosomes and synaptosomal membrane fraction from BLA; the enhancement of presynaptic glutamate release by D1 receptor agonist upon chronic morphine treatment was dependent on the activation of cAMP-dependent protein kinase; and the intra-BLA injection of D1 receptor antagonist canceled the conditioned place aversion (CPA) in morphine-dependent rats. In conclusion, chronic morphine treatment switches the effect of DA on the excitatory synaptic transmission from inhibition to excitation by the presynaptic D1 receptor amount increase-mediated glutamate release in the pyramidal cells of BLA and the blockade of D1 receptors in BLA cancels CPA in morphine-dependent rats.

Whether fat is beneficial or detrimental to bones is still controversial, which may be due to inequivalence of the fat mass. Our objective is to define the effect of body fat and its distribution on bone quality in healthy Chinese men. A total of 228 men, aged from 38 to 89 years, were recruited. BMD, trabecular bone score (TBS), and body fat distribution were measured by dual-energy X-ray absorptiometry. Subcutaneous and visceral fat were assessed by MRI. In the Pearson correlation analysis, lumbar spine BMD exhibited positive associations with total and all regional fat depots, regardless of the fat distribution. However, the correlation disappeared with adjusted covariables of age, BMI, HDL-C, and HbA1c%. TBS was negatively correlated with fat mass. In multiple linear regression models, android fat (and not gynoid, trunk, or limbs fat) showed significant inverse association with TBS (β = −0.611, P < 0.001). Furthermore, visceral fat was described as a pathogenic fat harmful to TBS, even after adjusting for age and BMI (β = −0.280, P = 0.017). Our findings suggested that body fat mass, especially android fat and visceral fat, may have negative effects on bone microstructure; whereas body fat mass contributes to BMD through mechanical loading.

BackgroundDrug addiction is a chronic brain disorder characterized by the compulsive use of drugs. The study of chronic morphine-induced adaptation in the brain and its functional significance is of importance to understand the mechanism of morphine addiction. Previous studies have found a number of chronic morphine-induced adaptive changes at molecular levels in the brain. A study from our lab showed that chronic morphine-induced increases in the expression of D1 receptors at presynaptic terminals coming from other structures to the basolateral amygdala (BLA) played an important role in environmental cue-induced retrieval of morphine withdrawal memory. However, the neurocircuitry where the increased D1 receptors are located and how chronic morphine increases D1 receptor expression in specific neurocircuits remain to be elucidated.ResultsOur results show that chronic morphine induces a persistent increase in D1 receptor expression in glutamatergic terminals of projection neurons from the medial prefrontal cortex (mPFC) to the BLA, but has no influence on D1 receptor expression in projection neurons from the hippocampus or the thalamus to the BLA. This adaptation to chronic morphine is mediated by reduced expression of miR-105 in the mPFC, which results in enhanced D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA. Ex vivo optogenetic experiments show that a chronic morphine-induced increase in D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA results in sensitization of the effect of D1 receptor agonist on presynaptic glutamate release. mPFC to BLA projection neurons are activated by withdrawal-associated environmental cues in morphine-withdrawal rats, and overexpression of miR-105 in the mPFC leads to reduced D1 receptor induction in response to chronic morphine in glutamatergic terminals of the projection neurons from the mPFC to the BLA, and a reduction in place aversion conditioned by morphine withdrawal.ConclusionsThese results suggest that chronic morphine use induces a persistent increase in D1 receptors in glutamatergic terminals of projection neurons from the mPFC to the BLA via downregulation of miR-105 in the mPFC, and that these adaptive changes contribute to environmental cue-induced retrieval of morphine withdrawal memory.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0467-2) contains supplementary material, which is available to authorized users.

No abstract