Comparison of Brain-derived Neurotrophic Factor Level in Depressed Patients Treated with Fluoxetine and Sertraline

Background: The Brain-Derived NeurotrophicFactor (BDNF) is the main neuronal growth factor in the brain that regulates neurogenesis, neuronal maturity, synaptic formation and plasticity. Studies showed BDNF level decreased in depression and the administration of anti depressant drugs increased BDNF level. In this study, we used fluoxetine and sertraline, which are Selective Serotonin Reuptake Inhibitor (SSRI) but had a different mechanism in influencing the BDNF levels. The purpose of this study was to compare the effect of fluoxetine and sertraline administration tothe BDNF level in depressed subjects. This study was conducted at Wahidin Sudirohusodo Hospital, Makassar, Indonesia and its affiliates from January to February 2019. Twenty outpatient subjects were diagnosed with depression based on DSM-V. The subjects were either antidepressant naïve, or dropping out of antidepressant therapy for at least 3 months since the last administration. Blood samples from each subject were taken by consecutive sampling, and BDNF levels were analyzed before and after administration of fluoxetine and sertraline for six weeks. Also, Hamilton Depression Rating Scale (HDRS) scores are measured before and after administration. The BDNF serum was significantly increased by 100.6% (p<0,001) from the baseline level in the fluoxetine group and 75.4% in the sertraline group. HDRS score was decreased by39.5% (p<0,001) in the fluoxetine group and 30.1% in the sertraline group after six weeks of administration. This study suggests that fluoxetine was superior to sertraline in increasing the BDNF level in depression.

Tissue-Specificity of Antibodies Raised Against TrkB and p75NTR Receptors; Implications for Platelets as Models of Neurodegenerative Diseases

Platelets and neurons share many similarities including comparable secretory granule types with homologous calcium-dependent secretory mechanisms as well as internalization, sequestration and secretion of many neurotransmitters. Thus, platelets present a high potential to be used as peripheral biomarkers to reflect neuronal pathologies. The brain-derived neurotrophic factor (BDNF) acts as a neuronal growth factor involved in learning and memory through the binding of two receptors, the tropomyosin receptor kinase B (TrkB) and the 75 kDa pan-neurotrophic receptor (p75NTR). In addition to its expression in the central nervous system, BDNF is found in much greater quantities in blood circulation, where it is largely stored within platelets. Levels 100- to 1,000-fold those of neurons make platelets the most important peripheral reservoir of BDNF. This led us to hypothesize that platelets would express canonical BDNF receptors, i.e., TrkB and p75NTR, and that the receptors on platelets would bear significant resemblance to the ones found in the brain. However, herein we report discrepancies regarding detection of these receptors using antibody-based assays, with antibodies displaying important tissue-specificity. The currently available antibodies raised against TrkB and p75NTR should therefore be used with caution to study platelets as models for neurological disorders. Rigorous characterization of antibodies and bioassays appears critical to understand the interplay between platelet and neuronal biology of BDNF.

BDNF Expression in Cortical GABAergic Interneurons

Brain-derived neurotrophic factor (BDNF) is a major neuronal growth factor that is widely expressed in the central nervous system. It is synthesized as a glycosylated precursor protein, (pro)BDNF and post-translationally converted to the mature form, (m)BDNF. BDNF is known to be produced and secreted by cortical glutamatergic principal cells (PCs); however, it remains a question whether it can also be synthesized by other neuron types, in particular, GABAergic interneurons (INs). Therefore, we utilized immunocytochemical labeling and reverse transcription quantitative PCR (RT-qPCR) to investigate the cellular distribution of proBDNF and its RNA in glutamatergic and GABAergic neurons of the mouse cortex. Immunofluorescence labeling revealed that mBDNF, as well as proBDNF, localized to both the neuronal populations in the hippocampus. The precursor proBDNF protein showed a perinuclear distribution pattern, overlapping with the rough endoplasmic reticulum (ER), the site of protein synthesis. RT-qPCR of samples obtained using laser capture microdissection (LCM) or fluorescence-activated cell sorting (FACS) of hippocampal and cortical neurons further demonstrated the abundance of BDNF transcripts in both glutamatergic and GABAergic cells. Thus, our data provide compelling evidence that BDNF can be synthesized by both principal cells and INs of the cortex.

Different Effects of Cannabis Abuse on Adolescent and Adult Brain

Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in <i>Cannabis sativa</i> is tetrahydrocannabinol (THC). However, in the past 40 years the content of the psychoactive ingredient THC in most of the preparations is not constant but has increased due to other breeding and culturing conditions. THC acts as the endocannabinoids at CB1 and CB2 receptors but pharmacologically can be described as a partial (not a pure) agonist. Recent evidence shows that activation of the CB1 receptor by THC can diminish the production of neuronal growth factor in neurons and affect other signalling cascades involved in synapsis formation. Since these factors play an important role in the brain development and in the neuronal conversion processes during puberty, it seems reasonable that THC can affect the adolescent brain in another manner than the adult brain. Accordingly, in adolescent cannabis users structural changes were observed with loss of grey matter in certain brain areas. Moreover, recent studies show different effects of THC on adolescent and adult brains and on behaviour. These studies indicate that early THC abuse can result in neuropsychological deficits. This review gives an overview over the present knowledge in this field.

New opportunities in treatment of patients with discirculatory encephalopathy: emphasis on nervous growth factor

The paper presents the results of research on the role of neuronal growth factors in the development and progression of cognitive and psychoemotional disorders. Peculiarities of Bacopa Monier and Ginkgo Biloba influence on structural and functional changes of the brain in the experiment and in certain groups of patients are shown. The results of treatment with phytocomplex (FC) Memostim® (fixed combination of Bacopa Monier - 150 mg and Ginkgo Biloba - 120 mg) of 30 patients with DE II grade due to atherosclerosis and hypertension are described. The control group consisted of 30 patients with grade II DE who were not prescribed FC Memostim®. After 3 months of treatment with FC Memostim®, a decrease in the frequency and severity of cephalic, vestibulo-atactic and asthenic syndromes was observed in patients. There was a significant improvement in cognitive functions (on the MoSA scale) and psycho-emotional state of patients. There was a significant improvement in the calculated operations and attention (by 22% relative to baseline, p <0.05) and the overall score on the test (+ 8%, p> 0.05). The general tendency to improve visual-constructive functions, memory, speech, executive functions, abstract thinking and orientation has been identified. Similar results of the effect of FC Memostim® on cognitive functions were obtained from the FAB questionnaire. According to the results of the survey of patients on the scale of quality of life, a significant positive dynamics of the integrative index (statistically significant increase by 31%), index of psychological well-being (increase by 32%), self-satisfaction (by 28%), indicators of physical well-being (by 18%) after 3 months of treatment with FC Memostim®. The level of neuronal growth factor (β-NGF) increased statistically significantly (by 67%). The analysis of the obtained data testifies to the effectiveness and safety of FC Memostim® in the treatment of patients with DE. Thus, the obtained data demonstrate the profound effect of FC Memostim® on the symptoms of cognitive and psychoemotional disorders in patients with DE, which is associated with an increase in NGF levels on the background of the course.