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Acta Physiologica Hungarica, Volume 100 (4), pp. 388–394 (2013)DOI: 10.1556/APhysiol.100.2013.4.3

Molecular basis of chronic stress-induced hippocampal lateral asymmetry in rats and impact on learning

and memoryN Spasojevic, P Jovanovic, S Dronjak

Institute of Nuclear Sciences “Vinca”, Laboratory of Molecular Biology and Endocrinology, University of Belgrade, Belgrade, Serbia

Received: January 30, 2013Accepted after revision: June 24, 2013

Neurochemical lateralization has been demonstrated in the rat brain suggesting that such lateralization might contribute to behavior. Thus, the aim of the present study was to examine neurochemical asymmetry in the hippocampus, molecular basis of neurochemical lateralization and its impact on spatial learning and memory. Changes in noradrenaline content, tyrosine hydroxylase (TH) were studied in the right and left hippocampus of naive control and chronically isolated rats, by applying TaqMan RT-PCR and Western blot analysis. Hippocampal-based spatial learning and memory were evaluated using the Barnes maze. In control rats an asymmetrical right-left distribution of noradrenaline content and gene expression of catecholamine synthesizing enzyme was found. Chronic psychosocial stress further emphasized asymmetry. Isolation stress reduced noradrenaline content only in the right hippocampus. No changes were observed in gene expression and protein levels of TH in the right hippocampus, whereas expression of catecholamine synthesizing enzyme was elevated in the left hippocampus. Reduced noradrenaline content in the right hippocampus did not cause impairment in spatial learning and memory. Our fi ndings suggest that chronic psychosocial stress reduces noradrenaline stores in the right hippocampus which may be caused by molecular asymmetry, but it does not affect spatial learning and memory.

Keywords: asymmetry, hippocampus, noradrenaline, memory, rats

Cerebral lateralization is one of the well-known asymmetries. Right–left asymmetries are now known to be present in a variety of species, including rodents and humans (6, 9). Numerous brain regions show right–left asymmetries including hippocampus. The hippocampus is a sensitive brain structure that is involved in certain aspects of learning and memory (7). Cognitive and neurobiological studies have provided converging evidence that the hippocampus is critically involved in long-term memory formation (3, 16). Stress damages the hippocampal structures. The chronic stress increases the release of stress-dependent neurotransmitters such as noradrenaline, which has a signifi cant infl uence on cognitive functions (15). Chengzhi et al. (4) have found that noradrenaline is essential in memory formation. These authors reported that chronic noise exposure of young male rats reduced monoamine neurotransmitters in the hippocampus and impaired spatial learning and memory. It has been also demonstrated that presentation of a stressful stimulus can cause a rapid increase in the activity of catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) as well as in the extracellular concentration of noradrenaline in the brain (1). Aubert et al. (2) have found that hippocampal neurons possess

Corresponding author: Sladjana Dronjak, PhD Research ProfessorInstitute of Nuclear Sciences “Vinca” Lab. Mol. Biol. Endocrinol.11000 Belgrade, Serbia PO Box 522-090 Phone/Fax: +381-112455561; E-mail: sladj@vinca.rs