Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet.

Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

Differential Influence of Amyloid-ß on the Kinetics of Dopamine Release in the Dorsal and Ventral Striatum of Rats.

Dopaminergic dysfunction is a part of Alzheimer's disease pathology. The brain accumulation of amyloid-ß of toxic form is a key link of the pathology, which, according to the literature, is also true for dopaminergic dysfunction. An increase in the amyloid-ß level in the brain changes the maximum of the evoked dopamine release in the dorsal and ventral parts of the striatum of the experimental animals. Theoretically, this may be due to the change in the intensity of dopamine release from the nerve terminals or its reuptake. However, it has not been studied. To fill this gap, we examined the amyloid-ß induced changes in the kinetics of the evoked dopamine release in the dorsal striatum and the nucleus accumbens core and shell. Amyloid-ß solution (fragments 25-35) was injected into the ventricular system of the anesthetized male Wistar rats. Before and after injection, electrically evoked dopamine kinetics was registered with fast-scan cyclic voltammetry. The results had shown that the amount of dopamine release decreases in the dorsal striatum and increases in the nucleus accumbens shell. No changes were found in the intensity of dopamine reuptake.

Prefrontal mRNA expression of long and short isoforms of D2 dopamine receptor: Possible role in delayed learning deficit caused by early life interleukin-1ß treatment.

Long (D2L) and short (D2S) isoform of the D2 dopamine receptor are believed to play different roles in behavioral regulation. However, little is known about differential regulation of these isoforms mRNA expression during the process of learning in physiological and pathological states. In this study, we have investigated the combined effect of training in active avoidance (AA) paradigm and chronic early life treatment with pro-inflammatory cytokine interleukin (IL)-1ß (1µg/kg i.p., P15-21) on D2S and D2L dopamine receptor mRNA expression in the medial prefrontal cortex (mPFC) of adult rats. We have shown differential regulation of D2 short and long mRNA isoform expression in the mPFC. There was no effect of AA-training on D2S mRNA expression, while D2L mRNA was downregulated in AA-trained control (intact and saline-treated) animals, and this effect was not observed in rats treated with IL-1ß. D2S mRNA expression level negatively correlated with learning ability within control (saline-treated and intact) groups but not in IL-1ß-treated animals. Thus, prefrontal expression of distinct D2 dopamine receptor splice variants is supposed to be implicated in cognitive decline caused by early life immune challenge.

Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models.

Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy.

The Pavlov Department of Physiology: a scientific history.

The scientific adventure of the Ivan Pavlov Department of Physiology is traced from Pavlov's and his students pioneer work on "psychic salivation" to the times of the Biological Station at Koltushi. The development of the Department after Pavlov's death is described and the research trends of the three present laboratories (Neurobiology of Integrative Brain Functions, Psychophysiology of Emotions, and Neurodynamic Correction of Psycho Neurological Pathology) are discussed.