Agnieszka Nikiforuk, PhD

More publications
  • The effects of positive allosteric modulators of alpha7 nicotinic acetylcholine receptors on complex cognitive processes - 2013-07-12 - 2016-07-12
    α7 nicotinic acetylcholine receptors (α7-nAChRs) play important role in the regulation of complex cognitive functions which may be impaired in a number of psychiatric disorders. Moreover, it has been suggested that the α7-nAChRs may be implicated in the pathogenesis of schizophrenia. Therefore, in recent years, α7-nAChRs arouse a great interest as a target for the development of pharmacological treatment of cognitive dysfunctions in schizophrenia. The activity of α7-nAChR can be modulated be either orthosteric agonists or positive allosteric modulators (PAMs). Despite numerous preclinical evidences, the procognitive action of direct α7-nAChR agonist has not been conclusively confirmed in patients with schizophrenia. Allosteric modulation is thought to be associated with more favourable and more specific action. Hence, α7-nAChR PAMs may represent more promising tool. While several α7-nAChR PAMs have been recently developed, their behavioural effects, including their potential impact on cognitive processes, have not been yet extensively characterised. Our research hypothesis is based on the presumption that the action of PAMs may differ from the effects induced by orthosteric receptor activation. It is suggested by PAM-induced retardation of rapid desensitization, a fundamental feature of α7-nAchR. Therefore, the aim of the proposed project is to examine the effects of α7-nAChR PAM in comparison to orthosteric agonists in animal tasks assessing cognitive domains that are important from the perspective of cognitive deficits encountered in schizophrenia (e.g., executive functions, attention, and working memory).
  • The evaluation of the efficacy of ligands of alpha7 nicotinic acetylcholine receptors in models of autism in rats
    Autism spectrum disorders (ASD), one of the most common neurodevelopmental disorders, are now a major public health and social concern throughout the world. The ASD symptoms are grouped in two main diagnostic criteria: social/communicative deficits and restricted, repetitive patterns of behaviours. These symptoms manifest themselves at early childhood, persist into adulthood and limit or impair everyday life. ASD is also accompanied by diversity of comorbid features, as for example, anxiety, hyperactivity, impulsivity, inattention, irritability, sensory abnormalities, aggressive behaviour and cognitive deficits. One of the most troublesome aspects of ASD is that the number of patients has strikingly increased in the last years. As a consequence, costs relating to the treatment and care of ASD patients are also dramatically rising.Pharmacologic treatment of ASD is mainly targeted at co-occurring problems. Thus, there is an urgent need for a new pharmacotherapy that can effectively treat the core symptomatology of the disease, particularly in the social/communication domain. A wide body of evidence points to the role of cholinergic system, including alpha 7 nicotinic acetylcholine receptors (α7-nAChR), in the pathophysiology of ASD and pharmacotherapy of this disorder. Nevertheless, the strategy based on a direct activation of α7-nAChR has not yet been assessed for the efficacy against core symptoms of ASD in either clinical or preclinical studies. The research hypothesis of our project is that the selective targeting of α7-nAChR can address both core symptom domains and co-morbid impairments. To test this hypothesis we plan to assess the efficacy of selective α7-nAChR ligands (the agonist and positive allosteric modulators) in neurodevelopmental ASD models in rats. Behavioural studies will be complemented by the assessment of neurochemical changes. The results of the proposed study will provide a preclinical framework for targeting α7-nAChR ligand as a pharmacotherapy of ASD.