Rolipram improves cognition, reduces anxiety- and despair-like behaviors and impacts hippocampal neuroplasticity after transient global cerebral ischemia

Is your doctor doing anything for you despair, anxiety or cognition. Mine did nothing.  I do wonder how they know mice are despairing or have anxiety?
http://www.sciencedirect.com/science/article/pii/S0306452216300495

• Lígia Mendes Soares^a,
• Jochen De Vry^b,
• Harry W.M. Steinbusch^b,
• Humberto Milani^a,
• Jos Prickaerts^b,
• Rúbia M. Weffort de Oliveira^{a, ,}

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doi:10.1016/j.neuroscience.2016.03.062

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Highlights

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Rolipram improves cognition, reduces anxiety- and despair-like behaviors after BCCAO.

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Rolipram decreases hippocampal neurodegeneration induced by BCCAO.

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Rolipram increases DCX- and MAP-2 expression in the hippocampus of BCCAO mice.

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Abstract

Cognitive impairment, anxiety- and depressive-like symptoms are well recognized outcome of cerebral ischemia in clinical and preclinical settings. Rolipram, a phosphodiesterase-4 (PDE-4) inhibitor, improves cognition and produces anxiolytic- and antidepressant-like effects in rodents. Rolipram also exerts anti-inflammatory effects and enhances survival of newborn hippocampal neurons in mice subjected to transient global cerebral ischemia. Here, we evaluated the effects of chronic rolipram treatment in mice subjected to transient global brain ischemia. C56B6/7 mice were subjected to bilateral common carotid artery occlusion (BCCAO) and were then tested in a multi-tiered behavioral battery including the elevated zero maze (EZM), open field (OF), object location test (OLT), and forced swim test (FST). We also investigated the effects of rolipram on hippocampal neurodegeneration and the expression of the neuronal plasticity markers doublecortin (DCX) and microtubule-associated protein (MAP-2). Ischemic mice exhibited memory deficits OLT, higher levels of anxiety EZM and behavioral despair FST. BCCAO caused neuronal loss in the CA3 hippocampal subfield and basolateral amygdala (BLA). In the hippocampus of BCCAO mice, a disrupted neuronal plasticity was evidenced by decreased DCX expression. Chronic treatment with rolipram attenuated the behavioral effects of BCCAO. Rolipram also decreased neurodegeneration in the CA3 while it increased dendritic arborization of DCX-immunoreactive (DCX-IR) neurons and microtubule associate MAP-2 expression in the hippocampus of BCCAO mice. These data suggest that chronic inhibition of PDE-4 can be a useful therapeutic strategy to improve the emotional and cognitive outcomes of transient global cerebral ischemia.

Abbreviations

• BCCAO, bilateral common carotid artery occlusion;
• BLA, basolateral amygdala;
• cAMP, cyclic adenosine monophosphate;
• CREB, cAMP-responsive element binding protein;
• DAB, 3-3′-diaminobenzidine;
• DCX, doublecortin;
• DCX-IR, DCX-immunoreactive;
• EZM, elevated zero maze;
• FST, forced swim test;
• GCL, granular cell layer;
• MAP-2, microtubule-associated protein;
• MAP-2, microtubule-associated protein;
• OF, open field;
• OLT, object location test;
• PDE-4, phosphodiesterase-4;
• PKA, protein kinase A;
• SGZ, subgranular zone

Key words

• rolipram;
• bilateral common carotid artery occlusion;
• neuroprotection

Corresponding author. Tel: +55-44-30115165; fax: +55-44-30114999.

Copyright © 2016 Published by Elsevier Ltd.

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