Neonatal Proinflammatory Stress Induces Accumulation of Corticosterone and Interleukin-6 in the Hippocampus of Juvenile Rats: Potential Mechanism of Synaptic Plasticity Impairments.

Infectious diseases in early postnatal ontogenesis can induce neuroinflammation, disrupt normal central nervous system development, and contribute to pathogenesis of cerebral pathologies in adults. To study long-term consequences of such early stress, we induced neonatal proinflammatory stress (NPS) by injecting bacterial lipopolysaccharide into rat pups on postnatal days 3 and 5 and then assessed the levels of corticosterone, proinflammatory cytokines and their mRNAs, and neurotrophins and their mRNAs in the hippocampus and neocortex of the one-month-old animals. Long-term potentiation (LTP) was studied in hippocampal slices as an index of synaptic plasticity. NPS-induced impairments of LTP were accompanied by the accumulation of corticosterone and IL-6 in the hippocampus. In the neocortex, a decrease in exon IV BDNF mRNA was detected. We suggest that excessive corticosterone delivery to hippocampal receptors and proinflammatory changes persisting during brain maturation are among the principal molecular mechanisms responsible for NPS-induced neuroplasticity impairments.

Effects of intranasal administration of the peptide antagonist of type I vaniloid receptor (TRPV1) in the rodent central nervous system.

Intranasal administration of the polypeptide APHC3, an antagonist of the TRPV1 receptor, had acute anxiolytic and antidepressant effects, as well as an ability to modify the microglial response to proinflammatory stress and cytokine profile of the hippocampus. However, the acute antidepressant effect of the polypeptide was not related to the attenuation of neuroiflammation and probably had a different mechanism. The use of intranasal administration of the APHC3 peptide as a therapeutic approach aimed at decreasing depression symptoms needs additional studies in order to find the mechanism of action of this polypeptide in the central nervous system (CNS).

[The Effects of Chronic Combined Stress: Changes in Behavior of Rats with Various Responses to Novelty].

We studied the effect of chronic combined stress (model of experimental neurosis) on behavior of rats with different basal strategies of behavior in novelty conditions. Chronic stress resulted in decreases in the body weight and testosterone contents in the blood and neocortex in all animals. Animals with initially low orient- ing-exploratory response in the "open field" test did not exhibit substantial alterations of behavior during repeated testing in this test of the "dark-light chamber" test; however, the depression-like behavior was more expressed in the second forced swim test. Chronic combined stress did not significantly affect the behavior of this group of rats. Animals with initially high orienting-exploratory response in the "open field" test exhibited decreased locomotor and exploratory activity in the repeated "open field" tests. The decreases in the locomotor and exploratory activity were substantially less expressed in the repeated tests in these rats after chronic combined stress. The indices of depression-like behavior increased one month after the end of exposure to chronic combined stress. Our data demonstrate that different responses to novelty in the "open field" test do not allow predict with reasonable certainty the development of depression-like behavior after exposure to chronic combined stress.

[CHANGES OF THE CEREBRAL CORTEX AFTER DOSED TRAUMATIC BRAIN INJURY IN RATS OF DIFFERENT AGES].

Using dosed lateral fluid percussion, moderate and severe traumatic brain injury (TBI) was modeled in one- and two-year-old rats. Brain sections were stained using the Nissl cresyl violet method and an immunohistochemical reaction was performed for the demonstration of glial fibrillary acidic protein (GFAP), a marker of astrocytes. The results obtained indicate the formation in the cerebral cortex, ipsilateral to the impact, the zones of direct and remote of injury. The zone of direct injury corresponded to the area of immediate contact of the liquid column with the dura mater, whereas the remote area of damage was located laterally and caudally to the former. Morphological signs of the injury depended on the force of impact and were manifested in both age groups by astrocytic gliosis and the thinning of layer I of the cortex resulting from neuronal death. The emergence of ischemia-modified neurons, probably, was due to a local disruption of the blood supply. Disorders in the brain in one-year-old rats had a local character and those in two-year-old rats were diffuse, while gliosis was inhomogeneous. The reproducibility and adequacy of the model allow its use for research of molecular-genetic mechanisms of TBI outcomes in humans, as well as for the identification of common mechanisms of TBI consequences and the pathogenesis of the major diseases, comorbid with TBI, primarily depression and epilepsy.

[Functions of microglia in the healthy brain: focus on neuroplasticity].

Microglia is in the center of modern research because it is involved in neuroinflammation processes, which is considered as an important part of pathogenesis of many brain pathologies. On the contrary, normal physiological functions of microglia are less studied. Here we review modern data on functioning of microglia in the healthy brain. We consider involvement of microglia in angiogenesis, neurogenesis, synaptogenesis, long-term potentiation, and the mechanisms of microglia-neuron interaction. We further consider modern concept on active interaction of microglia with neurons in developing and healthy mature brain and the essential role of microglia in neuroplasticity mechanisms at various levels.