Acute morphine administration, morphine dependence, and naloxone-induced withdrawal syndrome affect the resting-state functional connectivity and Local Field Potentials of the rat prefrontal cortex.

Opiates are among the widely abused substances worldwide. Also, the clinical use of opioids can cause unwanted and potentially severe consequences such as developing tolerance and dependence. This study simultaneously measured the changes induced after morphine dependence and naloxone-induced withdrawal syndrome on the resting-state functional connectivity (rsFC) and Local Field Potential (LFP) power in the prefrontal cortex of the rat. The obtained results revealed that acute morphine administration significantly increased the LFP power in all frequency bands, as well as the rsFC strength of the prefrontal cortex, and naloxone injection reversed this effect. In contrast, chronic morphine administration reduced neural activity and general correlation values in intrinsic signals, as well as the LFP power in all frequency bands. In morphine-dependent rats, after each morphine administration, the LFP power in all frequency bands and the rsFC strength of the prefrontal cortex were increased, and these effects were further enhanced after naloxone precipitated withdrawal syndrome. The present study concludes that general correlation merely reflects the field activity of the local cortices imaged.

Measuring the Frequency-Specific Functional Connectivity Using Wavelet Coherence Analysis in Stroke Rats Based on Intrinsic Signals.

Optical intrinsic signal imaging (OISi) method is an optical technique to evaluate the functional connectivity (FC) of the cortex in animals. Already, using OISi, the FC of the cortex has been measured in time or frequency domain separately, and at frequencies below 0.08 Hz, which is not in the frequency range of hemodynamic oscillations which are able to track fast cortical events, including neurogenic, myogenic, cardiac and respiratory activities. In the current work, we calculated the wavelet coherence (WC) transform of the OISi time series to evaluate the cerebral response changes in the stroke rats. Utilizing WC, we measured FC at frequencies up to 4.5 Hz, and could monitor the time and frequency dependency of the FC simultaneously. The results showed that the WC of the brain diminished significantly in ischemic motor and somatosensory cortices. According to the statistical results, the signal amplitude, responsive area size, correlation, and wavelet coherence of the motor and the somatosensory cortices for stroke hemisphere were found to be significantly lower compared to the healthy hemisphere. The obtained results confirm that the OISi-based WC analysis is an efficient method to diagnose the relative severity of infarction and the size of the infarcted region after ischemic stroke.

Human cardiomyocytes undergo enhanced maturation in embryonic stem cell-derived organoid transplants.

Human cardiomyocytes (CM) differentiated from pluripotent stem cells (PSCs) are relatively immature when generated in two-dimensional (2D) in vitro cultures, which limits their biomedical applications. Here, we devised a strategy to enhance maturation of human CM in vitro by assembly of three-dimensional (3D) cardiac organoids (CO) containing human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs), endothelial cells (ECs), and mesenchymal stem cells (MSCs). In contrast to corresponding 2D cultures, 3D CO not only developed into structures containing spontaneously beating CM, but also showed enhanced maturity as indicated by increased expressions of sarcomere and ion channel genes and reduced proliferation. Heterotopic implantation of CO into the peritoneal cavity of immunodeficient mice induced neovascularization, and further stimulated upregulation of genes coding for the contractile apparatus, Ca2+ handling and ion channel proteins. In addition, CM in implanted CO were characterized by a more mature ultrastructure compared to CM implanted without CO support. Functional analysis revealed the presence of working cardiomyocytes in both in vivo and ex ovo chorioallantoic membrane implanted CO. Our results demonstrate that cultivation in 3D CO and subsequent heterotopic implantation enhance maturation of CM towards an adult-like phenotype. We reason that CO-derived CM represent an attractive source for drug discovery and other biomedical applications.