Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients

Ana-Maria Buga, Ovidiu Ciobanu, George Mihai Bădescu, Catalin Bogdan, Ria Weston, Mark Slevin, Mario Di Napoli and Aurel Popa-Wagner _

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Oncotarget. 2016; 7:17415-17430. https://doi.org/10.18632/oncotarget.8277

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Abstract

Ana-Maria Buga1,2,*, Ovidiu Ciobanu2,6,*, George Mihai Bădescu7, Catalin Bogdan2, Ria Weston3, Mark Slevin3, Mario Di Napoli4,5 and Aurel Popa-Wagner1

1 Department of Psychiatry and Psychotheraphy, University of Medicine Rostock, Rostock, Germany

2 Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy Craiova, Craiova, Romania

3 Department of Healthcare Science, Manchester Metropolitan University, Manchester, UK

4 Neurological Service, San Camillo de’ Lellis General Hospital, Rieti, Italy

5 Neurological Section, SMDN—Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L’Aquila, Italy

6 Vivantes Humboldt-Klinikum, Center for Affective Disorders, Berlin, Germany

7 Psychiatry Clinical Hospital, University of Medicine and Pharmacy of Craiova, Craiova, Romania

* These authors have contributed equally to this work

Correspondence to:

Aurel Popa-Wagner, email:

Keywords: aging; stroke; post-stroke depression; serotonin receptor type B; neurogenesis; Gerotarget

Received: February 04, 2016 Accepted: March 14, 2016 Published: March 22, 2016

Abstract

Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke.


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