Cognitive Training as a Potential Activator of Hippocampal Neurogenesis in the Rat Model of Sporadic Alzheimer's Disease.

Alena O Burnyasheva,Natalia A Stefanova,Ekaterina A Rudnitskaya,Tatiana A Kozlova,Nataliya G Kolosova

doi:10.3390/ijms21196986

Abstract

There is a growing body of evidence that interventions like cognitive training or exercises prior to the manifestation of Alzheimer’s disease (AD) symptoms may decelerate cognitive decline. Nonetheless, evidence of prevention or a delay of dementia is still insufficient. Using OXYS rats as a suitable model of sporadic AD and Wistar rats as a control, we examined effects of cognitive training in the Morris water maze on neurogenesis in the dentate gyrus in presymptomatic (young rats) and symptomatic (adult rats) periods of development of AD signs. Four weeks after the cognitive training, we immunohistochemically estimated densities of quiescent and amplifying neuronal progenitors, neuronal-lineage cells (neuroblasts and immature and mature neurons), and astrocytes in young and adult rats, and the amyloid precursor protein and amyloid-β in adult rats. Reference memory was defective in OXYS rats. The cognitive training did not affect neuronal-lineage cells’ density in either rat strain either at the young or adult age, but activated neuronal progenitors in young rats and increased astrocyte density and downregulated amyloid-β in adult OXYS rats. Thus, to activate adult neurogenesis, cognitive training should be started before first neurodegenerative changes, whereas cognitive training accompanying amyloid-β accumulation affects only astrocytic support.

Highlights

Alzheimer’s disease (AD) is a detrimental multifactorial disorder developing asymptomatically for many years prior to its manifestation [1]
It is well known that adult neurogenesis occurring in the hippocampal dentate gyrus (DG) of mammals results in the integration of newborn granule cells into the hippocampus circuitry, providing an extra degree of plasticity that is crucial for the acquisition of certain types of contextual memory [8]
Wistar rats learned the location of the submerged platform starting from the second training day (p < 0.009); whereas OXYS rats started successfully finding the platform on the third training day (p < 0.02; Figure 1A)

Summary

Introduction

Alzheimer’s disease (AD) is a detrimental multifactorial disorder developing asymptomatically for many years prior to its manifestation [1]. Several studies have revealed positive associations of physical activity, cognitive training, or both with cognition in elderly people and patients with mild cognitive impairment [5,6,7]. These cognitive improvements may be explained by the activation of neuroplasticity. Physical exercise and cognitive training activate neurogenesis in the hippocampal DG of adult animals [9,10] It is still unclear at what age cognitive training should be started to improve cognitive function [11] because the precise mechanisms underlying cognitive improvement in elderly people are still unknown, and this research is difficult because of limitations of human studies as well as the absence of suitable animal models for the late-onset sporadic form of AD

Methods

Results

Conclusion