SPC365

Physical exercise or atenolol: what is the best strategy to counteract the behavioral modifications induced by low doses of doxorubicin?

Session: CO 05 - Ciência Básica
Speaker: Ângela Raquel Amaro Leal

Congress: CPC 2021
Topic: O. Basic Science
Theme: 36. Basic Science
Subtheme: 36.6 Basic Science - Other
Session Type: Comunicações Orais
FP Number: ---
Authors: Ângela Raquel Amaro Leal; Filipa Machado; Ana i. Afonso; isabel rocha; Vera Geraldes
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Doxorubicin-induced cognitive impairment and cardiovascular disorders are widely recognized as common complications of cancer therapies, which dramatically deteriorates the patients&rsquo; quality of life, preventing them from restoring their pre-cancer life.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Often termed &ldquo;chemobrain&rdquo;, these anatomical and functional cardiac changes, including the autonomic nervous system, could interfere with the control of different cognitive domains, with changes in various aspects of memory and executive function, and emotional factors, such as anxiety and depression. &nbsp;&nbsp;</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Different preventive strategies, such as beta-blockers or physical activity affect positively brain function and can prevent anthracycline-induced sympathoexcitation.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Thus, the current study was undertaken to test the hypothesis that beta-blockers or physical exercise can prevent or relieve Dox-induced cognitive and behavioral impairments. We also assess the relationship between heart rate variability (HRV), as a measure of autonomic nervous system (ANS) functioning, and behavioral performance in an animal model of low dose of doxorubicin (DOX).</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">For that, adult female Wistar rats (n=30), aged more than 20 weeks, were randomly divided into 3 groups, namely doxorubicin (DOX; ip cumulative dose 8mg/kg, 1 time/week, for 4 weeks), DOX with beta-blockers (DOX+ATN; Atenolol, OA 4 mg/ml, 5 times/week), DOX with exercise training (DOX+EXER; treadmill, 30 min to 22 cm/seg, 5x/week). Anxiety (elevated plus maze), locomotor activity (open-field test) and working memory (Y maze test) were analyzed 2 and 4 weeks after DOX initiation.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Overall, our results showed that low dose DOX therapy results in anxiety-like behavior over time and tended to reduce locomotor activity, without evidence of sympatho-excitation. Nevertheless, working memory were not affected. Atenolol treatment significantly increased the amount of time that DOX animals spent in the open arms of the elevated plus maze, mitigating the DOX induced-anxious behavior. This beta-blocker tended to increase locomotor activity and working memory over-time. Physical exercise protocol, similar to atenolol effect, tended to increase the time spent in the open arms, the total distance travelled and the percentage&nbsp;of alternation, suggesting improvements in locomotion and working memory and relieving anxiety associated with DOX therapy. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black">Although both pharmacological and non-pharmacological interventions appear to have a positive effect on behavioral function, atenolol had a more pronounced protective effect. Our preliminary results also provide additional evidence that an increased sympathetic activity, but not decreased parasympathetic activity, is associated with better cognitive performances. However, complementary biochemical and molecular analysis are needed to substantiate this claim.</span></span></span></span></p>