Autophosphorylation of αCaMKII regulates alcohol consumption by controlling sedative effects of alcohol and alcohol-induced loss of excitatory synapses.

Calcium/calmodulin-dependent kinase II (CaMKII) is a key enzyme at the glutamatergic synapses. CAMK2A gene variants have been linked with alcohol use disorder (AUD) by an unknown mechanism. Here, we looked for the link between αCaMKII autophosphorylation and the AUD aetiology. Autophosphorylation-deficient heterozygous αCaMKII mutant mice (T286A+/- ) were trained in the IntelliCages to test the role of αCaMKII activity in AUD-related behaviours. The glutamatergic synapses morphology in CeA was studied in the animals drinking alcohol using 3D electron microscopy. We found that T286A+/- mutants consumed less alcohol and were more sensitive to sedating effects of alcohol, as compared to wild-type littermates (WT). After voluntary alcohol drinking, T286A+/- mice had less excitatory synapses in the CeA, as compared to alcohol-naive animals. This change correlated with alcohol consumption was not reversed after alcohol withdrawal and not observed in WT mice. Our study suggests that αCaMKII autophosphorylation affects alcohol consumption by controlling sedative effects of alcohol and preventing synaptic loss in the individuals drinking alcohol. This finding advances our understanding of the molecular processes that regulate alcohol dependence.

Extremely Low Frequency-Electromagnetic Fields (ELF-EMF) Can Decrease Spermatocyte Count and Motility and Change Testicular Tissue.

Background: Substantial evidence indicates that exposure to extremely low frequency-electromagnetic fields (ELF-EMFs) affects male reproductive system. Objective: The goal of this study was to evaluate the effects of long-term irradiation with ELF-EMF on sperm quality and quantity and testicular structure. Material and Methods: In this case-control study, sixty male Sprague-Dawley rats were randomly divided into six groups. Experimental groups were exposed to ELF-EMF (50 Hz EMF, 100 µT) for either 1 h/day for 52 days (Group 1), 4 h/day for 52 days (Group 3), 1 h/day for 5 days (Group 5), 4 h/day for 52 days (Group 7). Groups 2, 4, 6 and 8 were only sham exposed at durations equal to Groups 1, 3, 5 and 7, respectively. Results: Both count and motility of sperms were significantly decreased in animals exposed to ELF-EMF (1 h/day for 52 days, 4 h/day for 52 day, and 4 h/day for 5 days) compared to the sham-exposed groups (P<0.05). Serum testosterone levels showed a significant decrease in the animals exposed to ELF-EMF (4 h/day for 5 days) compared to the control groups (P<0.05). A significant decrease was observed in the volume of the seminiferous tubules, seminiferous tubules epithelium and interstitial tissue in the animals exposed to ELF-EMF for 4 h/day for 5 days. Tubules length was also reduced by 18% in animals exposed to ELF-EMF (4 h/day for 5 days). Conclusion: Our results show that ELF-EMF can reduce spermatocyte count and motility and is able to induce structural changes in testicular tissue.

Optimisation of ketamine-xylazine anaesthetic dose and its association with changes in the dendritic spine of CA1 hippocampus in the young and old male and female Wistar rats.

BACKGROUND: A combination of ketamine-xylazine (K-X) is frequently used for anaesthesia in rats. Sex and age affect this cocktail dosage. Ketamine causes a hypnotic effect by blocking NMDA receptors located on the dendritic spine of the CA1 region. OBJECTIVES: The present study aimed to find the optimal dosage of K-X and its association with the changes in dendritic spine number of the CA1 region for aged and young rats of both sexes. METHODS: We injected 150-4 mg/kg of K-X in young and 100-2 mg/kg in aged Wistar rats intraperitoneally and recorded the onset time and duration of anaesthesia and death percentage. Then, animals were sacrificed, brains removed, cut and after Golgi-Cox staining, the total number of dendritic spines on CA1 was estimated. RESULTS: The findings showed that the onset time of anaesthesia lasted longer and its duration lasted shorter, and the number of mature spines decreased with aging, but sex caused no significant effect. The death percentages in young groups comprise 20% and in the aged groups were lower: 5% in males and 0.0% in females. CONCLUSIONS: It seems 100-2 mg/kg of K-X is an optimal dose in aged rats and retains an association with reduction of the mature dendritic spine of CA1.

The medial prefrontal cortex to the medial amygdala connections may affect the anxiety level in aged rats.

BACKGROUND: Aging changes brain function and behavior differently in male and female individuals. Changes in the medial prefrontal cortex (mPFC)-medial amygdala (MeA) connectivity affect anxiety-like behavior. OBJECTIVES: Therefore, this study aimed to investigate the effect of aging and sex on the mPFC-MeA connection and its association with the level of anxiety-like behavior. METHODS: We divided the Wistar rats into the male and female young rats (2-3-month-old) and male and female old rats (18-20 months old). First, the open field test (OFT) was performed, and then 80 nl of Fluoro-Gold (FG) was injected by stereotaxic surgery in the right or left MeA. After 10 days, the animals were perfused, their brain removed, coronal sections cut, and the number of FG-labeled cells in the right and left mPFC of each sample was estimated. RESULTS: Based on our results, old animals revealed less anxiety-like behavior than young ones, and young females were less anxious than young males, too. Interestingly, MeA of old male rats received more fibers from the bilateral mPFC than young ones. Also, this connection was stronger in the young females than young males. Altogether, the present study indicated that old individuals had less anxiety-like behavior and stronger mPFC-MeA connection, and young female rats were less anxious and had a stronger connection of mPFC-amygdala than males of the same age. CONCLUSION: Thus, it seems that there is a negative relationship between anxiety levels based on the rat's performance in the OFT apparatus and the mPFC-MeA connection.

Different paradigms of transcranial electrical stimulation improve motor function impairment and striatum tissue injuries in the collagenase-induced intracerebral hemorrhage rat model.

BACKGROUND: In the horizon of therapeutic restrictions in intracerebral hemorrhage (ICH), recently, non-invasive transcranial electrical stimulation (tES) has achieved considerable prosperities. Translational studies have postulated that transcranial direct current stimulation (tDCS) and the other types of tES remain potentially a novel therapeutic option to reverse or stabilize cognitive and motor impairments. OBJECTIVE: The aim of this study was to comparatively evaluate the effects of the four main paradigms of tES, including tDCS, transcranial alternating (tACS), pulsed (tPCS), and random noise (tRNS) stimulations on collagenase-induced sensorimotor impairments and striatum tissue damage in male rats. METHODS: To induce ICH, 0.5 µl of collagenase was injected into the right striatum of male Sprague Dawley rats. One day after surgery, tES, was applied to the animals for seven consecutive days. Motor functions were appraised by neurological deficit score, rotarod, and wire hanging tests on the day before surgery and postoperative days 3, 7, and 14. After behavioral tests, brain tissue was prepared appropriately to perform the stereological evaluations. RESULTS: The results indicated that the application of the four tES paradigms (tDCS, tACS, tRNS, and tPCS) significantly reversed motor disorders in collagenase-induced ICH groups. Further, the motor function improvement of tACS and tRNS receiving rats in wire-hanging and rotarod tests were higher than the other two tES receiving groups. Structural changes and stereological assessments also confirmed the results of behavioral functions. CONCLUSION: Our findings suggest that in addition to tDCS application in the treatment of ICH, other tES paradigms, especially tACS and tRNS may be considered as add-on therapeutic strategies in stroke.

Genomic and Phenotypic Analyses Reveal Mechanisms Underlying Homing Ability in Pigeon.

The homing pigeon was selectively bred from the domestic pigeon for a homing ability over long distances, a very fascinating but complex behavioral trait. Here, we generate a total of 95 whole genomes from diverse pigeon breeds. Comparing the genomes from the homing pigeon population with those from other breeds identifies candidate positively selected genes, including many genes involved in the central nervous system, particularly spatial learning and memory such as LRP8. Expression profiling reveals many neuronal genes displaying differential expression in the hippocampus, which is the key organ for memory and navigation and exhibits significantly larger size in the homing pigeon. In addition, we uncover a candidate gene GSR (encoding glutathione-disulfide reductase) experiencing positive selection in the homing pigeon. Expression profiling finds that GSR is highly expressed in the wattle and visual pigment cell layer, and displays increased expression levels in the homing pigeon. In vitro, a magnetic field stimulates increases in calcium ion concentration in cells expressing pigeon GSR. These findings support the importance of the hippocampus (functioning in spatial memory and navigation) for homing ability, and the potential involvement of GSR in pigeon magnetoreception.