Chemobrain in blood cancers: How chemotherapeutics interfere with the brain's structure and functionality, immune system, and metabolic functions.

Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well-being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy-induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood-brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo-drug's effects on cognition in cancer are not direct and/or in-direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy-induced cognitive impairment.

Minireview: Animal model of schizophrenia from the perspective of behavioral pharmacology: Effect of treatment on cognitive functions.

Schizophrenia is a debilitating mental disorder characterized by positive, negative and cognitive symptoms. Whereas positive symptoms are satisfactorily addressed by current antipsychotic treatment, negative and cognitive symptomatic treatment remains largely ineffective. This review investigates the treatment efficacy regarding cognitive symptoms and evaluates the contribution of different monoamine receptor systems involved in schizophrenia pathophysiology to cognition. In the review, we included preclinical studies assessing the effect of different treatments on cognition in pre-pulse inhibition and two spatial cognitive tests. While pre-pulse inhibition investigates pre-attentive processes operating outside of conscious awareness, the spatial tasks require continuous attention and active engagement in task solving for a successful outcome. The schizophrenia-like phenotype was attained by acute or subchronic administration of non-competitive NMDA receptor antagonist MK-801.

Place avoidance tasks as tools in the behavioral neuroscience of learning and memory.

Spatial navigation comprises a widely-studied complex of animal behaviors. Its study offers many methodological advantages over other approaches, enabling assessment of a variety of experimental questions and the possibility to compare the results across different species. Spatial navigation in laboratory animals is often considered a model of higher human cognitive functions including declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents was designed in our laboratory, originally named the place avoidance task, and later a modification of this approach was established and called active place avoidance task. It employs a continuously rotating arena, upon which animals are trained to avoid a stable sector defined according to room-frame coordinates. This review describes the development of the place avoidance tasks, evaluates the cognitive processes associated with performance and explores the application of place avoidance in the testing of spatial learning after neuropharmacological, lesion and other experimental manipulations.