[Telomere-telomerase system in aging, norm and pathology (literature review)].

This literature review presents results of research showing association between functional activity of the telomere-telomerase system and mental cognitive and emotional processes in normal and various pathological states: chronic stress, depression, bipolar disorder, schizophrenia, mild cognitive impairment and dementia in aging. It also refers to age-specific, psycho-social, economic, immunological, genetic and epigenetic factors that influence these relationships.

[THE INTEGRATIVE LEVEL OF THE HIERARCHICAL SYSTEM OF SPATIAL ORIENTATION OF ANIMALS].

The purpose of this review is to analyze the current knowledge about the higher, integrative level of the physiological system of orientation of animals in space. The significance of the study of this level caused by the fact that its disruption can cause deterioration of the capacity for spatial orientation (spatial agnosia) which is an important sign of some diseases of the brain, and in particular Alzheimer's disease. In recent decades, the main functional components of integration of information on space position of animals were discovered. The significance of these discoveries was reflected in a number of prestigious awards and honors, including the Nobel Prize in Physiology or Medicine for 2014.

[MECHANISMS OF NEURONAL LOSS IN ALZHEIMER''S DISEASE].

One of the main elements of the pathogenesis of Alzheimer's disease is neuronal loss in different areas of the brain, which is more intensive than in normal aging. Necessity of studying the pathogenesis of this process is determined by the fact that the loss of neurons begins at the preclinical stage of Alzheimer's disease when the amyloid plaques and neurofibrillary tangles (main morphological manifestations of the disease) is not yet formed and that the loss of neurons correlates with the severity of clinical symptoms. To date, there is evidence that allows delineating probable pathogenetic mechanisms of neuronal loss. This is the purpose of this review of the literature.

[Effects of activation of kappa-opioid receptors on the behavior at the postnatal development of the stress reactivity systems].

It is known that stress changes state and reactivity of humoral systems of stress, particularly the hypothalamic-pituitary-adrenal system (HPA) and the dynorphin-K-opioid system (DKOS) in any age periods, including ones of early postnatal development. Supposedly these changes are underlying some disorders. Difference in state and reactivity of the HPA system is well established. But the role of DKOS is not clear. Further study of this requires summarizing of the literature data on physiology of DKOS activation and ethological features of the activation in different periods of postnatal development. It is possible to conclude that the mode of reaction to stimulation of the DKOS differs in the early development in contrast to adult animals. The mode of reaction can be changed in relation to the periods of development of the system of stress-reactivity and can depend on prior activation of the stress system in a particular period.

[Ontogenetic peculiarities of regulation of apoptosis in hypothalamic neurosecretory cells in thf-knockout mice].

Tumor necrosis factor (TNF) participates in regulation of many processes including carcinogenesis and apoptosis. However, at present, there are practically absent the works on peculiarities of regulation of apoptosis in tnf-knockout (tnf-/-) mice. These mice develop without morphological abnormalities, but they seem to have disturbances of many biological processes, such as inflammation, programmed cell death, etc. Therefore, the goal of our work was to study possible pathways of regulation of apoptosis in the absence of TNF in neurosecretory cells (NSC) of young and old mice. For this purpose, we determined immunohistochemically expression of apoptosis markers caspase-8, -9. Bax, Bcl2, Mcl1, neuropeptide vasopressin, and the apoptosis level in hypothalamus in tnf-knockout mice of different ages as compared with mice with unchanged level of TNF synthesis. It was shown that the apoptosis activation observed during aging did not depend on the tnf gene, and apoptosis at aging was caspase-dependent. It has been revealed that at aging in mouse NSC the external cell death pathway with participation of caspase-8 is activated. The pathways mediating cell death in different neurosecretory centers at aging are different. Thus, in supraoptic nucleus (SON), in all studied animal groups, animal groups, an important cause of the NSC apoptosis is Bax. In paraventricular nucleus (PVN), of the greater importance is a decrease of the antiapoptotic protection. Hence, misbalance of synthesis of proteins of the Bcl-2 family plays an important role in development of senescent apoptosis.

Aging-related changes in the expression of apoptosis-associated molecules in neurosecretory cells of the mouse hypothalamus.

The aim of the present work was to identify the characteristics of the control of apoptosis in neurosecretory centers of aged (18 months) mice on exposure to the immunomodulator interferon-alpha (IA) in comparison with young (two months) mice. Age-related activation of apoptosis in the supraoptic (SON) and paraventricular (PVN) nuclei was found to be mediated by different pathways and could result from changes in the ratio of synthesis of pro-(Bax) and antiapoptotic (Mcl-1, Bcl-2) molecules. In addition, the apoptosis signal cascade in young mice treated with IA was identical in both nuclei, while in aged mice there were differences between the SON and the PVN.

[Changes in expression of apoptosis-associated molecules in hypothalamic neurosecretory cells of mice during aging].

The aim of work was to study the peculiarities of apoptosis regulation in neurosecretory centers of old (aged 18 months) mice treated with immunomodulator interferon alpha (IFN-alpha) as compared to young (aged 2 months) mice. It was shown that age-related apoptosis activation in supraoptic (SON) and paraventricular (PVN) nuclei was mediated by different molecular mechanisms and could result from the alterations of the balance of apoptosis-associated proteins, including the synthesis of proapoptotic (Bax) and antiapoptotic (Mcl-1, Bcl-2) molecules. Besides, the apoptosis signal cascade in young mice treated with IFN-alpha was identical in both nuclei, whereas in old mice there were some differences between SON and PVN.