Vol 10, No 1 (2016)

Adult neurogenesis is an intensively studied phenomenon that is presumably involved in brain functioning under normal and some pathological conditions. Neuroinflammation as a non-specific response of the nerve tissue to pathologic conditions may change the course of adult neurogenesis in the brain and thus enable long-term functional and structural alterations. In this short review, we discuss the interaction of adult neurogenesis and neuroinflammation with a special emphasis on the place that is occupied in both these processes by morphogenic proteins of the Wnt family, which play an important role in the development of the nervous system, as well as in the neuroplasticity of the adult brain.

This review describes the role of biogenic amines in the hypothalamic regulation of ovarian cycles in female rats. The mechanisms of action of industrial xenobiotics and experimental hyperhomocysteinemia, which induces premature aging of the reproductive function, are discussed. The point of view that the damaging action of reactive oxygen species is the basis of the unified response of hypothalamic regulation of reproductive cycles to external and internal neurotoxic impacts is substantiated. We describe the involvement of melatonin and short regulatory peptides in antioxidant protection of the reproductive system during aging.

A hypothetical mechanism for the influence of dopamine on the formation of neuronal representations of “object–place” associations in the hippocampus is proposed for spatial learning. According to this mechanism, dopamine that is released in a new situation or during expectation of reinforcement improves conditions for the development of homosynaptic long-term potentiation (LTP) of the input to the dentate gyrus granule cells from the medial entorhinal cortex, which transmits information about spatial location of objects and characteristics of objects. The effect occurs due to the activation of D1/D5 receptors on granule cells and D2 receptors on inhibitory interneurons. Heterosynaptic depression is simultaneously developed in inputs that were not activated. As a result, a contrasting representation of the learned “object–place” association is formed on neurons of the dentate gyrus. From these neurons, information about the association via the CA3 field is transmitted to the radial layer of the CA1 field by Schaffer collaterals, whereas the stratum lacunosum-moleculare receives signals directly from the entorhinal cortex and thalamic nucleus reuniens, which connects the hippocampus with the prefrontal cortex. The sign of the modulatory influence of dopamine on the efficacy of excitatory inputs to pyramid neurons of the CA1 field depends on the relationship between excitation and inhibition of these neurons, as well as the dopamine concentration. By acting on D1/D5 receptors on the pyramidal neurons of the CA1 field, dopamine can promote LTP induction in Schaffer collaterals simultaneously with LTP induction in the relatively strong perforant input, whereas relatively weak perforant input, as well as the input from the nucleus reuniens, become depressed. This depression is promoted by the activation of D1/D5 receptors on the inhibitory interneurons of the CA1 field, induction of LTP in these neurons, and the following enhancement of afferent inhibition of pyramidal cells. As a consequence, neuronal representation of the learned “object–place” association in the CA1 field is distorted more weakly by non-relevant information that comes from the entorhinal cortex and thalamus. As a result, the error probability during the performance of spatial task decreases. Because activation of D1/D5 receptors on pyramidal neurons of the prefrontal cortex promotes LTP induction in the input from the CA1 field, dopamine must improve the goal-directed performance of spatial tasks. The proposed mechanism explains the results of some experimental studies that seemed to be contradictory or incomprehensible.

We studied the features of choline acetyltransferase (ChAT) distribution in cholinergic structures of the central and peripheral nervous systems; specifically in the spinal cord and dorsal root ganglion (DRG) of embryo (E20), newborn, or adult rats using a goat polyclonal antibody. We found that this anti-ChAT antibody selectively labels both central and peripheral cholinergic structures. We observed cholinergic neurons with weak immunoreactivity. We demonstrated that at all stages of ontogeny that we studied, four groups of cholinergic neurons occurred in the cervical part of the spinal cord, viz., the small neurons of the dorsal horns, neurons of Rexed’s lamina X, neurons of the area of Rexed’s laminae VI–VII, and cells of the ventral horns. Interneurons of Rexed’s laminae VI–VII exhibited maximum ChAT reactivity as compared to other groups of cholinergic neurons of the spinal cord at all developmental stages we studied. We found an increase in the number of immunopositive cells of lamina X from E20 stage to the early postnatal and mature stages. In the peripheral cholinergic structures, i.e., the DRG, of the rat, all neurons expressed ChAT at all stages of ontogeny.

The effects of exercise stress following single semax and selank administration on the activity of carboxypeptidase E and phenylmethylsulfonyl fluoride-inhibited carboxypeptidase, which are basic carboxypeptidases that are involved in the final stage of processing of biologically active neuropeptide precursors, was studied. The enzyme activity was shown to increase during exercise stress, as well as in response to administration of the peptide agents prior to exercise. The role of basic carboxypeptidases in the mechanisms of semax- and selank-induced stimulation and in the activation of the peptidergic system during physical exercise is discussed.

Oxidative stress and inflammation are deemed to play a vital role in diabetic cerebral and neurological dysfunction. The present study was designed to investigate the protective effect of the naturally occurring antioxidant, lutein, against oxidative injury and inflammation in cerebral cortex (CCT) of diabetic animals. Using single IP injection of streptozotocin (STZ, 65 mg/kg) diabetes was induced in rats. Lutein dietary supplement was provided to diabetic animals for 5 consecutive weeks in three different doses. The extent of lipid peroxidation and cellular damage were estimated in CCT. Endogenous antioxidants molecules such as non-protein sulfhydryl groups (NP-SH) and enzymes including superoxide dismutase (SOD) and catalase (CAT) were also estimated in CCT. Levels of neurotrophic factors such as brain derived nerve factor (BDNF), nerve growth factor (NGF) and insulin growth factor (IGF) and pro-inflammatory cytokines, as markers for neural inflammation, were assessed in CCT. Lutein dietary supplement, significantly inhibited the diabetes induced increased in CCT levels of thiobarbituric acid reactive substances (TBARS), caspase-3, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. Diabetes caused inhibition in the levels of NP-SH, DNA and RNA was significantly increased following lutein dietary supplementation to diabetic group compared to normal diet fed animals in dose dependent manner. Diabetes induced down regulation of BDNF, NGF and IGF was also attenuated by lutein dietary supplementation to diabetic model for 5 weeks. These findings suggest that lutein has the potential to ameliorate diabetes-induced oxidative and inflammatory damage and neural degeneration in the CCT.

We compared the level of substance P in 28 patients with the acute phase of carotid ischemic stroke at day 1 and 3 of the development of the disease. The concentration of substance P in the blood serum of patients with severe stroke was higher than in the serum of patients with the mild and medium form of the disease, as well as in the control blood-serum samples. The data we obtained suggest that the peptide plays an important role during ischemic lesion of the brain.

Diabetic polyneuropathy (DN) is the most frequent neurological complication in diabetes mellitus (DM) patients. This study examines dyslipidemia and levels of lipid peroxidation in the plasma and erythrocytes of patients with type 2 DM in relation to the presence or absence of DN, and analyzes the possible impact of gender in the course of DN. There were no statistically significant differences between genders in the clinical or electrophysiological findings of DN (p > 0.05). The lipid parameters approached higher values in all DM patients in comparison to the control subjects (p < 0.05). No significant differences were detected between lipid values in DM with DN and without DN (p > 0.05). The obtained TBARS values in plasma and erythrocytes were higher in DM patients than in the control subjects. TBARS values in all study patients with DN (women and men) approached higher values than in the patients without DN (p > 0.05), but the only significant difference was found in the erythrocytes in women with DN compared to those without DN (p < 0.05). Based upon the data presented here, the lipid peroxidation in the cell and disturbed lipid profile that we observed in patients with type 2 DM and DN are more pronounced in women than in men. This suggests that women have a relatively higher risk for DN than men.