Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias

The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression

NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981. Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25-6981 was administered (protocol days 6–7) followed by retraining (days 15–18 or 29–32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol. Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29–32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment. Chronological analysis indicated a possible involvement of new mature neurons in the reconfiguration of memory processes. This was attended by behavioral/gene correlations which revealed direct links between spatial memory retrieval enhancement and modified gene activity induced by NR2B/NMDA receptor blockade and upregulation

Tobacco smoking dependence in patients with depressive spectrum mental disorders: clinical, pathogenetic, and therapeutic aspects

This review considers the clinical and pathogenetic aspects of an association between tobacco smoking dependence and depressive spectrum disorders. The comorbidity of these disorders has been established to be to a large extent determined by their common genetic bases. This association substantially affects the efficiency of treatment. Resistance to anti-nicotine and antidepressant medications is associated precisely with the comorbidity of these diseases. To enhance the efficiency of treatment, it is promising to include non-drug methods into the therapeutic complex. This makes it possible to achieve a gradual reduction in tobacco withdrawal syndrome and to prevent an exacerbation of comorbid depression

Behavioral Patterns and Expression of Genes Coding Serotonin Receptors in Rats with Ultrasound Induced Depression

Aims: The aim of our study was to investigate the effects of continuous action of ultrasonic waves of variable frequencies on behavior of rats in "classical" tests used to reveal depression-like behavior, to evaluate the influence of different psychotropic drugs on rates of these tests and to analyze expression of several genes involved in pathogenesis of depression. Study Design: Rats in individual cages were exposed to ultrasonic irradiation for 21 days. Place and Duration of Study: V.P. Serbsky National Recearh Center For Social and Forensic Psychiatry, Department of Basic and Applied Neurobiology, Moscow, Russian Federation, between November 2012 and January 2013. Methodology: 48male non-pedigree albino rats were divided into 5 groups: nonultrasound- saline, ultrasound-saline, ultrasound-fluoxetine, ultrasound-bupropion and ultrasound-tianeptine. After 21 days of irradiation social interaction test, forced swimming test and sucrose preference test (anhedonia test) were conducted. Than rats were decapitated and prefrontal cortex were taken for RT-qPCR gene expression analysis of 5-HT1A, 5-HT2A, 5HT1B, 5HT2B receptors and SERT. Results: Depression-like behavior manifests itself in reduced social activity in social interaction test, increased immobility in forced swimming test and lower sucrose consumption in anhedonia test. The administrated antidepressants demonstrated their effectiveness, except for bupropion in the social interaction test. RT-qPCR gene expression analysis showed reduced expression of 5HT2A receptor gene and increased expression of SERT gene in the prefrontal cortex of rats stressed with ultrasonic radiation. Conclusion: The obtained data allow to conclude that further investigations with lager number of animals, extended tests battery may allow to claim that this model meets the main requirements set to animal models (face, predictive and construct validity) and can be used in studies of depression-like disorders caused by a situation of informational uncertainty and in pre-clinical development of new antidepressants

Analysis of NAPA gene expression in brain structures of Wistar Rats during the formation of long-term spatial memory and physical activity under stress situation

In the cerebellum, hippocampus, and prefrontal cortex of mature male Wistar rats with trained spatial navigational skill in the Morris water maze, the transcriptional activity the NAPA gene that regulates the transport and secretion of synaptic vesicles, release of neurotransmitters, and protein degradation was determined by real-time PCR. Animals subjected to forced swimming in a time-matched regime (active control) and naïve rats were used as the comparison groups. Suppression of NAPA gene activity was found in the hippocampus and cerebellum of the active control group, while navigation skill training led to a significant increase in gene expression in all brain structures under study. The findings suggest the existence of specific mechanisms regulating NAPA gene activity during the formation of spatial memory and adaptive behavior under stress conditions