Rat hippocampal GABAergic molecular markers are differentially affected by ageing

Apr 5, 2003Journal of neurochemistry

Age-related changes in brain chemical signals that reduce activity in the rat memory area

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Abstract

A differential age-related decrease in specific GABAergic mRNA levels was observed in the hippocampus of aged rats.

The expression of somatostatin and neuropeptide Y mRNAs decreased in 75% of aged animals, indicating a significant vulnerability.
Calretinin and vasoactive intestinal peptide mRNAs were affected in 50% of aged animals, while parvalbumin mRNA decreased in 25%.
An inverse correlation was found between the decrease in these mRNAs and the up-regulation of the alpha1 GABA receptor subunit.
Somatostatin interneurones, which primarily innervate distal dendrites of principal cells, showed greater vulnerability compared to calretinin interneurones.
Parvalbumin interneurones, which target the perisomatic domain of principal cells, were preserved, suggesting selective vulnerability among interneuronal subpopulations.

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We previously reported that the pharmacological properties of the hippocampal GABAA receptor and the expression of several subunits are modified during normal ageing. However, correlation between these post-synaptic modifications and pre-synaptic deficits were not determined. To address this issue, we have analysed the mRNA levels of several GABAergic molecular markers in young and old rat hippocampus, including glutamic acid decarboxylase enzymes, parvalbumin, calretinin, somatostatin, neuropeptide Y and vasoactive intestinal peptide (VIP). There was a differential age-related decrease in these interneuronal mRNAs that was inversely correlated with up-regulation of the alpha1 GABA receptor subunit. Somatostatin and neuropeptide Y mRNAs were most frequently affected (75% of the animals), then calretinin and VIP mRNAs (50% of the animals), and parvalbumin mRNA (25% of the animals) in the aged hippocampus. This selective vulnerability was well correlated at the protein/cellular level as analysed by immunocytochemistry. Somatostatin interneurones, which mostly innervate principal cell distal dendrites, were more vulnerable than calretinin interneurones, which target other interneurones. Parvalbumin interneurones, which mostly innervate perisomatic domains of principal cells, were preserved. This age-dependent differential reduction of specific hippocampal inteneuronal subpopulations might produce functional alterations in the GABAergic tone which might be compensated, at the post-synaptic level, by up-regulation of the expression of the alpha1 GABAA receptor subunit.

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Rat hippocampal GABAergic molecular markers are differentially affected by ageing

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