Placenta-Derived Mesenchymal-like Adherent Stromal Cells as an Effective Cell Therapy for Cocaine Addiction in a Rat Model.

Recent research points to mesenchymal stem cells' potential for treating neurological disorders, especially drug addiction. We examined the longitudinal effect of placenta-derived mesenchymal stromal-like cells (PLX-PAD) in a rat model for cocaine addiction. Sprague-Dawley male rats were trained to self-administer cocaine or saline daily until stable maintenance. Before the extinction phase, PLX-PAD cells were administered by intracerebroventricular or intranasal routes. Neurogenesis was evaluated, as was behavioral monitoring for craving. We labeled the PLX-PAD cells with gold nanoparticles and followed their longitudinal migration in the brain parallel to their infiltration of essential peripheral organs both by micro-CT and by inductively coupled plasma-optical emission spectrometry. Cell locations in the brain were confirmed by immunohistochemistry. We found that PLX-PAD cells attenuated cocaine-seeking behavior through their capacity to migrate to specific mesolimbic regions, homed on the parenchyma in the dentate gyrus of the hippocampus, and restored neurogenesis. We believe that intranasal cell therapy is a safe and effective approach to treating addiction and may offer a novel and efficient approach to rehabilitation.

The Effect of Dehydroepiandrosterone Treatment on Neurogenesis, Astrogliosis and Long-Term Cocaine-Seeking Behavior in a Cocaine Self-Administration Model in Rats.

Cocaine addiction is an acquired behavioral state developed in vulnerable individuals after cocaine exposure. It is characterized by compulsive drug-seeking and high vulnerability to relapse even after prolonged abstinence, associated with decreased neurogenesis in the hippocampus. This addictive state is hypothesized to be a form of "memory disease" in which the drug exploits the physiological neuroplasticity mechanisms that mediate regular learning and memory processes. Therefore, a major focus of the field has been to identify the cocaine-induced neuroadaptations occurring in the usurped brain's reward circuit. The neurosteroid dehydroepiandrosterone (DHEA) affects brain cell morphology, differentiation, neurotransmission, and memory. It also reduces drug-seeking behavior in an animal model of cocaine self-administration. Here, we examined the long-lasting effects of DHEA treatment on the attenuation of cocaine-seeking behavior. We also examined its short- and long-term influence on hippocampal cells architecture (neurons and astrocytes). Using a behavioral examination, immunohistochemical staining, and diffusion tensor imaging, we found an immediate effect on tissue density and activation of astrocytes, which has a continuous beneficial effect on neurogenesis and tissue organization. This research emphasizes the requites concert between astrocytes and neurons in the rehabilitation from addiction behavior. Thus, DHEA may serve as a treatment that corrects brain damage following exposure to and abstinence from cocaine.

Dehydroepiandrosterone and Addiction.

Drug addiction has a great negative influence on society, both social and economic burden. It was widely thought that addicts could choose to stop using drugs if only they had some self-control and principles. Nowadays, science has changed this view, defining drug addiction as a complex brain disease that affects behavior in many ways, both biological and psychological. Currently there is no ground-breaking reliable treatment for drug addiction. For more than a decade we are researching an alternative approach for intervention with drug craving and relapse to its usage, using DHEA, a well-being and antiaging food supplement. In this chapter we navigate through the significant therapeutic effect of DHEA on the brain circuits that control addiction and on behavioral performance both in animal models and addicts. We suggest that an integrative program of add-on DHEA treatment may further enable to dynamically evaluate the progress of rehabilitation of an individual patient, in a comprehensive assessment. Such a program may boost and support the detoxification and rehabilitation process, and help patients regain a normal life in a shorter amount of time.

Efficacy of temporal processing training to improve phonological awareness among dyslexic and normal reading students.

One of the leading theories for dyslexia suggests that it is the result of a difficulty in auditory temporal processing (ATP). This theory, as well as others, is supported by studies showing group differences and correlation between phonological awareness and ATP. However, these studies do not provide causal relationship. In the current study the authors aimed to test causal relationship between ATP and phonological awareness by comparing the performance of dyslexic and normal reader students in phonological awareness tasks before and after a short-term (5-day) training in either temporal processing (dichotic temporal order judgment; TOJ), nontemporal processing (intensity discrimination), or no training. TOJ training resulted in significant reduction of TOJ threshold and increase in phonological awareness tasks' scores. Intensity discrimination training resulted in a decrease of intensity discrimination threshold, but with no change in phonological awareness tasks. Those who had no training, had no change in TOJ and intensity discrimination thresholds, as well as in the phonological awareness tasks. These results show that (a) a short-term training in temporal processing with no other perceptual cues for adult dyslexic and normal readers can be efficient in improving their phonological awareness; and (b) phonological awareness (dis) ability has causal relationship to ATP.

Phosphorylation of SPICK2, an AKT2 channel homologue from Samanea motor cells.

SPICK2, a homologue of the weakly-inward-rectifying Shaker-like Arabidopsis K channel, AKT2, is a candidate K+-influx channel participating in light- and clock-regulated leaf movements of the legume, Samanea saman. Light and the biological clock regulate the in situ K+-influx channel activity differentially in extensor and flexor halves of the pulvinus (the S. saman leaf motor organ), and also-though differently-the transcript level of SPICK2 in the pulvinus. This disparity between the in situ channel activity versus its candidate transcript, along with the sequence analysis of SPICK2, suggest an in situ regulation of the activity of SPICK2, possibly by phosphorylation and/or by interaction with cAMP. Consistent with this (i) the activity of the voltage-dependent K+-selective fraction of the inward current in extensor and flexor cells was affected differentially in whole-cell patch-clamp assays promoting phosphorylation (using the protein phosphatase inhibitor okadaic acid); (ii) several proteins in isolated plasma membrane-enriched vesicles of the motor cells underwent phosphorylation without an added kinase in conditions similar to patch-clamp; and (iii) the SPICK2 protein was phosphorylated in vitro by the catalytic subunit of the broad-range cAMP-dependent protein kinase. All of these results are consistent with the notion that SPICK2 is the K+-influx channel, and is regulated in vivo directly by phosphorylation.

Plasma membrane aquaporins in the motor cells of Samanea saman: diurnal and circadian regulation.

Leaf-moving organs, remarkable for the rhythmic volume changes of their motor cells, served as a model system in which to study the regulation of membrane water fluxes. Two plasma membrane intrinsic protein homolog genes, SsAQP1 and SsAQP2, were cloned from these organs and characterized as aquaporins in Xenopus laevis oocytes. Osmotic water permeability (P(f)) was 10 times higher in SsAQP2-expressing oocytes than in SsAQP1-expressing oocytes. SsAQP1 was found to be glycerol permeable, and SsAQP2 was inhibited by 0.5 mM HgCl(2) and by 1 mM phloretin. The aquaporin mRNA levels differed in their spatial distribution in the leaf and were regulated diurnally in phase with leaflet movements. Additionally, SsAQP2 transcription was under circadian control. The P(f) of motor cell protoplasts was regulated diurnally as well: the morning and/or evening P(f) increases were inhibited by 50 microM HgCl(2), by 2 mM cycloheximide, and by 250 microM phloretin to the noon P(f) level. Our results link SsAQP2 to the physiological function of rhythmic cell volume changes.