Degeneration of astrocytes in the prefrontal cortex induces depressive-like behavior in rats: Behavioral, immunochemical and histological studies

• Autorzy: Smialowska M. , Szewczyk B. , Wawrzak-Wlecial A. , Domin H.
• Języki publikacji: EN

Abstrakty

EN

Postmortem studies of depressed patients showed that one of the most consistent findings is a decrease in the density of glial cells in human brain cortical regions, especially in the prefrontal and cingular areas. Furthermore, a decline in the number of astrocytes in the prefrontal cortex was found in rats after chronic unpredictable stress – one of the generally accepted animal models of depression. An important function of astrocytes in the brain tripartite synapse is the uptake of released glutamate. Hence the basic consequence of the loss of astrocytes is a reduction in glutamate uptake and an excess of glutamate in the synaptic cleft. The glutamatergic predominance in the excitator-inhibitory balance is postulated to be involved in the pathogenesis of depression. Recently, depressive-like behavior have been demonstrated in rats after astrocytes ablation. Therefore in the present study we tried to ascertain whether astroglial degeneration in the prefrontal cortex was sufficient to induce a depressive-like behavior and could serve as an animal model of depression. Astrocytic toxin L- or D,Lalpha-aminoadipic acid (AAA), 100 µg/2 µl, was microinjected bilaterally into rat medial prefrontal cortex (PFC). The toxins were injected twice, on day 1 and 2; afterwords depressive-like behavior was assessed by a forced swim test on day 5 of the experiment. Some rats were additionally treated with the antidepressant imipramine (30 mg/kg, i.p.) 24, 5 and 1 h before the forced swim test. The rats’ brains were taken out for an analysis on day eight. Histological verifications of the injection sites and immunohistochemical staining for the astrocytic marker glial fibrillary acidic protein (GFAP), were carried out. The GFAP positive cells were stereologically counted in the PFC. Also the level of GFAP expression was determined by the Western blot analysis in all the experimental groups. It was found that both L-AAA and DL-AAA induced a significant increase in immobility time in the forced swim test, without changing the overall locomotor activity, which indicates depressive-like effects of these compounds. The immunohistochemical and Western blot analyses showed a significant decrease in the number of GFAP-positive cells and GFAP level in the PFC of toxin-treated rats. The decrease amounted to ca. 50%. Both the behavioral and the GFAP changes were reversed or partially inhibited by imipramine injection. The obtained results suggest an important role of astrocytes in the PFC in mood regulation; moreover, they indicate that the degeneration of astrocytes in this structure may be used as an animal model of depression. This study was supported by Grant POIG.01.01.02-12-004/09Friday, November 23, 2012

Słowa kluczowe

EN

degeneration; astrocyte; prefrontal cortex; depression-like behaviour; rat; behaviour; immunochemistry; histology; depressed patient; glial cell; brain; cortical region; animal model; depression; medial prefrontal cortex

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.178

Twórcy

autor

Smialowska M.

• Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Szewczyk B.

• Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Wawrzak-Wlecial A.

• Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Domin H.

• Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland