Ontogenetic and Phylogenetic Approaches for Studying the Mechanisms of Cognitive Dysfunctions

Abstract

This chapter summarizes the phylogenetic and ontogenetic approaches for studying cognitive disorders such as Alzheimer's disease. It gives an extended example of evaluation of animal behavior and brain properties using an original model of prenatal hypoxia in rats by various physiological, behavioral, immunohistochemical, molecular biological, and biochemical techniques at different stages of postnatal development, which provide a better understanding of the pathological processes in the human brain during the development of neurodegeneration.

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

“…Antioxidants, in particular epigallocatechin gallate (EGCG), which was shown to increase NEP expression in cell models (Melzig and Janka, 2003 ), were also found capable to improve neurological deficits in our model of rat prenatal hypoxia (Zhuravin et al, 2018 ) and in a mouse model of Alzheimer's disease (Chang et al, 2015 ). The increase in NEP activity correlated with an improvement of rat performance in the radial maze and with restoration of both short- and long-term memory in the novel object recognition test (Zhuravin et al, 2011 , 2018 ; Nalivaeva et al, 2012 ).…”

“…Animal studies also provide evidence that preeclampsia-like conditions leading to increased blood pressure, proteinuria, growth restriction and, in the most severe cases, intrauterine mortality also resulted in increased apoptotic cell death in the fetal brain with the most sensitive areas being the subventricular and pallidum zones (Pellicer et al, 2011 ). Despite the existence of various protective mechanisms during embryogenesis and at birth, exposure of the embryonic brain to maternal hypoxia results in a number of changes in its structure and functional properties (Gross et al, 1981 ; Vasilev et al, 2016a , b ; Zhuravin et al, 2018 ).…”

“…The hypoxic conditions are achieved by replacing oxygen with nitrogen down to 7% O 2 concentration (or other desired level) during 10 min and then remaining at this level for 3 h. This paradigm provides a reliable and reproducible setting for maintaining hypoxic conditions and obtaining the material for further experiments either from the fetuses or rat pups during different stages of their postnatal development. The detailed analysis of the data obtained in these studies has recently been reviewed in Zhuravin et al ( 2018 ). Below we shall discuss the main effects of prenatal hypoxia on rat brain anatomical, biochemical and functional properties (Figure 2 ) comparing the results of our studies with the data of other research groups employing different hypoxia paradigms.…”

“…As we have also observed, prenatal hypoxia on E14 resulted in a decrease in the number of VAChT-positive cholinergic terminals which form synapses on the bodies of the pyramidal neurones in layers V-VI of the parietal cortex. On the other hand, the EAAT levels were found to be much higher in hypoxic animals resulting in spontaneous epileptogenic activity and increased kindling in response to pharmacological agents and other external stimuli (Zhuravin et al, 2018 ) and even a weak electric shock could induced seizure episodes in 1.5 years old rats subjected to prenatal hypoxia on E14 with more pronounced average duration than in control animals (Kalinina et al, 2015 ).…”

Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia

“…As shown in our studies in rats, prenatal hypoxia on embryonic days E13–14, when the generation and migration of the cells into the forming cortical areas take place [ 3 ], leads to delayed development of pups’ motor reactions and long-lasting cognitive dysfunctions observed at various stages of ontogenesis and underlined by impaired synaptic plasticity [ 4 , 5 , 6 ]. Along with the functional and structural alterations caused in animals by prenatal hypoxia, substantial rearrangements at the molecular and metabolic levels were observed in their nervous system.…”