Research Plan

Research aim 1: Synthesis of substances influencing glutamatergic neurotransmission  

• Research objective 1: Biological and pharmacological properties of new NMDAr inhibitors  
  • Activity 1. Neuropharmacology of potential medicaments with dual modulation of the cholinergic and glutamatergic system
  • Activity 2. Biological properties of new dual molecules influencing excitability of the CNS
• Research objective 2: Blockade of specific branches of the kynurenine metabolic pathway  
  • Activity 1. Inhibition of production of kynurenic acid as a new antipsychotic mechanism of the effect of pharmaceuticals
  • Activity 2. Antidepressant and neuroprotective influence of inhibition of quinolinic acid production
• Research objective 3: Multireceptor activity of neuroactive steroids (E. Kudová)  
  • Activity 1. Neurosteroids with positive allosteric effect at NMDA receptors
    Institutions/researchers involved:
    1. Institute of Physiology CAS (IPHYS): Prof. Ladislav Vyklicky, M.D., Ph.D., D.Sc.
    2. Institute of Organic Chemistry and Biochemistry (IOCB): RNDr. Eva Kudová, Ph.D.
    There has been more than 16 years of fruitful cooperation between IPHYS and IOCB in the research of steroid-induced modulation of NMDAR activity - numerous papers were published in prestigious international journals and five patents accepted. In addition, we have recently established cooperation with MUDr. Milos Petrovic, PhD. from University of Central Lanceshire.
• Research objective 4: Infrastructure for the monitoring of molecular basis of neurological disorders  
  • Activity 1. Monitoring of neurochemical background of CNS disorders
  • Activity 2. Drug delivery systems for new API´s dual modulating cholinergic and glutamatergic system
  • Activity 3. Introduction of GLP / GMP for drug synthesis

Research aim 2: Creation of new clinically relevant animal models  

• Research objective 1: Study of glutamatergic neurotransmission in neurodevelopmental models of CNS disorders  
  • Activity 1. Role of inflammatory mechanism in seizure development in perinatal period
  • Activity 2. Effect of perinatal stress on glutamatergic system
  • Activity 3. The effect of relapses on progression of schizophrenia in novel model of psychotic relapses
  • Activity 4. The role of glutamatergic neurotransmission in the development of dependency on methamphetamine
  • Activity 5. The effect of the long-term tonic excitation by light et night (LAN) in early postnatal development on circadian clock maturation, brain neurochemistry and vulnerability to circadian disruption by secondary insults later in life
• Research objective 2: Study of naturally occurring modulators of glutamatergic neurotransmission  
  • Activity 1. Study of Kynurenine Pathway Metabolism: Shared theory of affective and psychotic disorder pathophysiology
  • Activity 2. The role of neurosteroid in development of behavioral disease

Research aim 3: Therapy of Mental Disorders and their Relationship to the Neurotransmission of Glutamate  

• Research objective 1: Glutamatergic pharmaceuticals in clinical practice  
  • Activity 1. Neurobiology of the antidepressant effect of ketamine in the light of modulation of kynurenine cascade
• Research objective 2. Non-pharmacological effects of glutamatergic neurotransmission in the therapy of neurogenerative disorders: mechanisms and efficacy of cognitive remediation and stimulation methods  
  • Activity 1. Options of cognitive remediation using a progressive cognitive training for schizophrenia and bipolar disorder
  • Activity 2. Options of cognitive remediation by means of a progressive cognitive training for a mild cognitive impairment
  • Activity 3. Augmentation (enhancer) of pharmacotherapy using non-pharmacological methods– influencing of glutamatergic transmission in target areas of the brain (stimulation methods - rTMS, tDCS)
• Research objective 3. Development of new methods using virtual reality for a cognitive remediation for neuropsychiatric disorders in connection with the glutamatergic transmission  
  • Activity 1. Development of applications for remediation of a disrupted speed of information processing (flexibility, psychomotor tempo, cognitive coordination)
  • Activity 2. Development of virtual games for a cognitive training with a focus on memory functions
  • Activity 3. Development of new methods for a cognitive training for obsessive-compulsive type disorder with a focus on inhibitory control