Hypertension is a serious disease characterized by a sustained or recurrent increase in blood pressure, which can lead to various complications. Here, we studied the effect of genetically determined arterial hypertension in rats on their adaptation to long-term isolation and subsequent response to acute restraint stress. Male SHR rats with spontaneous hypertension were maintained in individual cages for 14 weeks. The serum levels of corticosterone, glucose, and pro- and anti-inflammatory cytokines and salivary α-amylase activity were studied, and the expression of genes associated with the regulation of steroidogenesis in the adrenal glands was evaluated. There were no significant changes in the parameters of the hypothalamic–pituitary–adrenocortical and sympatho-adrenal systems after isolation. Nevertheless, the preliminary isolation significantly affected the response to moderate restraint stress, including the expression of the regulatory genes Fkbp5 and Star in the adrenal glands and the content of proinflammatory cytokines IL-1β and IL-6 in the blood, although the changes in these indices were relatively subtle. This may reflect the predisposition of animals in isolation to develop quite specific stress-related changes.

—Nerve growth factor (NGF) is a factor which determines neuronal differentiation. NGF plays an important role in growth and differentiation of sensory and sympathetic neurons in the peripheral nervous system. In the mature brain, NGF is involved in the maintenance of the cholinergic neuronal phenotype. Here, we studied a possibility to induce the cholinergic phenotype in mouse neuroblastoma cells, which are often used to model various physiological and pathological processes occurring in the nervous system. Cells of NB41A3 and Neuro2a neuroblastoma lines are most frequently used to study the properties of cholinergic neurons. In the cells of these lines, the expression of TrkA and p75NGFR receptors, which is specific for the forebrain cholinergic nuclei, was revealed. Differentiation of the cells was induced by application of NGF or 8-Br-cAMP. NGF did not induce neuronal differentiation. Moreover, we did not find any changes in the content of choline acetyltransferase and vesicular acetylcholine transporter mRNA and protein, which were used as markers of the cholinergic phenotype. Thus, NB41A3 and Neuro2a cell lines cannot be advised as a model of cholinergic neurons in vitro because they do not differentiate and/or exhibit signs of the cholinergic phenotype in response to NGF stimulation.

Rodent models of deprivation of parental care are increasingly used to model depression-like disorders induced by early stress. The present study used a model of the consequences of mothers and offspring being kept in conditions of nesting material deficiency (NMD) for a prolonged period in early postnatal ontogeny in rats. The aim of this study was to determine whether the behavior of male rats exposed to stress due to being kept in conditions of NMD in the early postnatal period changes and whether any such changes are associated with impairments to the animals’ stress reactivity. Keeping of rats in conditions of NMD from postnatal day 2 to postnatal day 9 did not lead to any significant changes in measures of behavior pointing to anxiety and depressivity recorded in standard tests (open field test, elevated plus maze, sucrose solution preference) either in adolescence or adulthood. NMD in the early postnatal period produced an increase in social attachment (extent of socially oriented behavior manifest as the desire to spend more time in the presence of an unfamiliar individual in a novel context) in one-month-old but not adult animals. Keeping in conditions of NMD improved spatial learning but had no effect on long-term memory in adult rats on assessment of the ability of adults to learn to solve a spatial task in the Barnes maze. Changes in stress reactivity in animals (dynamics of release of corticosterone into the blood) were most marked in adult rats. Thus, NMD in the early postnatal period did not induce anxiety or depression-like behavior in male rats at ages 1 or 6 months but had transient effects on social attachment in young animals and altered stress reactivity on short-term exposure to a moderate stressor (restraint).

Olfactory bulbectomy in rodents is widely used as a model of the symptoms of clinical depression and neurodegeneration, including cholinergic. Male C57BL/6 mice in the present study underwent olfactory bulbectomy. Formation of long-term nonassociative memory (habituation) and spatial memory were studied two and four weeks after surgery. The effect of bulbectomy on the state of neurons in the medial septal area was studied using immunohistochemical staining for choline acetyltransferase and NeuN at the end of the behavioral studies, i.e., four and seven weeks after surgery. Bulbectomy led to impaired habituation in terms of measures of motor activity in the open field test and impaired spatial learning, but not memory in a water maze at both time points. A decrease in the proportion of cholinergic cells in the medial septal area was seen at four but not seven weeks after surgery. There were no significant changes in the total number of neurons in this part of the brain. Thus, the occurrence of cognitive impairment after olfactory bulbectomy may be associated with the manifestations of transient cholinergic deficit at the early stages of the development of pathology.

Rodent models of parental care deprivation are often used for reproduction of depressive-like disorders induced by early life stress. In the present study we used a model in which mother and litter are housed under the limited bedding and nesting (LBN) conditions during early postnatal ontogeny to evaluate its consequences. The aim of the study was to investigate whether the behavior of male rats that have experienced stress due to the exposure to LBN environment in the early postnatal period changes with age, and whether these changes are associated with an impairment of the stress-responsiveness of animals. The housing of rat pups in the LBN conditions during postnatal day 2 - day 9 did not result in significant alterations of anxiety- or depressive-like behavior observed in the standard tests, including the open field test, elevated plus-maze test, sucrose preference test in either adolescent or adult animals. However, the exposure to LBN increased social attachment or socially-oriented behavior, which was expressed in the desire to spend more time in the presence of an unfamiliar individual in a new environment, in 1-month-old but not adult rats. The exposure to LEN improved spatial learning but did not affect long-term memory in adult rats trained to perform a spatial task in the Barnes' maze. Changes in the stress-responsiveness, evaluated using blood corticosterone release, were more expressed in adult animals. Thus, the exposure to LBN in the early postnatal period did not result in the development of anxiety- or depressive-like behavior in land 6-month-old male rats; it transiently affected social attachment in young animals and modified response to short-term mild stressor.

Background: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer’s disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer’s disease. Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. Methods: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. Results: The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. Conclusion: We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer’s disease.

Removal of the olfactory bulbs induces a multitude of behavioral impairments, the most reproducible of which is hyperlocomotion. Olfactory bulbectomy is widely used to model anxiety and depression-like states. In the present study, C57Bl/6 mice subjected to olfactory bulbectomy were tested in standard tests to assess anxiety and depression-like behavior. Removal of the olfactory bulbs in mice was found to increase anxiety and emotionality. Attention in the present work was focused on the fact that hyperactivity induced by bulbectomy can seriously distort the results obtained in anxiety tests. The results lead to the conclusion that the contribution of hyperlocomotion must be taken into account in the interpretation of behavioral measures in the elevated plus maze test.

Olfactory bulbectomy causes multiple behavioral impairments, including hyperlocomotion, the main and most reproducible effect. Olfactory bulbectomy is widely used for anxiety and depression modeling. In the present study, male C57B1/6 mice were subjected to olfactory bulbectomy and then, studied in the standard test for estimation of anxiety and depressive-like behavior. The emotionality and anxiety have been increased in mice after olfactory bulbectomy. Olfactory bulbectomy induced in mice hyperactivity, which significantly affected their behavior in most tests. We concluded that the effects of hyperlocomotion should be taken into account for interpretation of animal behavior in an elevated plus maze.