Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement

doi:10.1016/S0306-4522(00)00050-6

Neuroscience

Volume 97, Issue 2, April 2000, Pages 253-266

https://doi.org/10.1016/S0306-4522(00)00050-6 Get rights and content

Abstract

We recently demonstrated that stress-induced cognitive deficits in rats do not correlate with hippocampal neuronal loss. Working on the premise that subtle structural changes may however be involved, we here evaluated the effects of chronic stress on hippocampal dendrite morphology, the volume of the mossy fiber system, and number and morphology of synapses between mossy fibers and CA3 dendritic excrescences. To better understand the mechanisms by which stress exerts its structural effects, we also studied these parameters in rats given exogenous corticosterone. Further, to search for signs of structural reorganization following the termination of the stress and corticosterone treatments, we analysed groups of rats returned to treatment-free conditions. All animals were assessed for spatial learning and memory performance in the Morris water maze. Consistent with previous findings, dendritic atrophy was observed in the CA3 hippocampal region of chronically stressed and corticosterone-treated rats; in addition, we observed atrophy in granule and CA1 pyramidal cells following these treatments. Additionally, profound changes in the morphology of the mossy fiber terminals and significant loss of synapses were detected in both conditions. These alterations were partially reversible following rehabilitation from stress or corticosterone treatments. The fine structural changes, which resulted from prolonged hypercortisolism, were accompanied by impairments in spatial learning and memory; the latter were undetectable following rehabilitation.

We conclude that there is an intimate relationship between corticosteroid levels, hippocampal neuritic structure and hippocampal-dependent learning and memory.

Section snippets

Animals and treatments

Male Wistar rats (Gulbenkian Institute of Science, Oeiras, Portugal) were used in this study. All studies were performed in accordance with the European Communities Council Directives of 24 November 1986 (86/609/ECC) and Portuguese Act no. 129/92. Animals were maintained under standard laboratory conditions (light/dark cycle of 12/12 h; temperature at 22°C; free access to food and drink). The following groups (n=10), were formed by random pooling animals from different litters aged two months:

Behavioral performance

Place learning. The overall repeated-measures ANOVA showed that rats in all groups progressively improved their ability to locate the platform over the 12 days of training (F_5,225=97.23, P<0.0005). Although the main effect of treatment on the performance of rats in place learning was non-significant, ANOVA revealed a significant group × trial block interaction (F_20,225=1.69, P<0.05). Post hoc comparisons showed that STR rats swam significantly longer distances to find the platform than CONT, on

Stress induces neuritic degeneration

The present stochastic analysis of the dendrites of the main hippocampal neuronal populations confirmed previous reports that stress results in CA3 apical dendrite atrophy.40., 68. Specifically, we found that stress induces a widespread reduction of the total dendritic length and a reduction in the distal dendritic branching density as a consequence of the shorter length of the terminal segments. However, in contrast to other reports,⁶³ we did not detect increases in the number of thorny

Acknowledgements

This work was supported by PRAXIS/2/2.1./SAU/1338/95.

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Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement

Abstract

Section snippets

Animals and treatments

Behavioral performance

Stress induces neuritic degeneration

Acknowledgements

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Brain Res.

The dendritic trees of neurons from the hippocampal formation of protein-deprived adult rats. A quantitative Golgi study

Expl Brain Res.

Evidence of reorganization in the hippocampal mossy fiber synapses of adult rats rehabilitated after prolonged undernutrition

Expl Brain Res.

Estimation of surface area from vertical sections

J. Microsc.

Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life

Science

Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment

Behav. Neurosci.