NEUROPROTECTIVE EFFECTS OF 17ß-ESTRADIOL ADMINISTRATION ON DOPAMINERGIC SYNTHESIS IN AN ANIMAL MODEL OF PARKINSON DISEASE

MARÍA PAULA BONACCORSO MARINELLI; GÓMEZ SILVINA; VALDEZ, SUSANA RUTH; CABRERA RICARDO JORGE

Mar del Plata

Congreso; Reunión Anual de las Sociedades de Biociencias 2019; 2019

SAIC-SAFE-SAB-SAP-NANOMED-Ar-ACCyTAL

We investigate estrogen neuroprotective actions in adult male rat braintissue after neurotoxic injury. Using inmunohistochemical techniques (IHQ), welabel and localize neurons that express tyrosine hydroxylase (TH) on substantianigra (SN) and their projections to corpus striatum (CPu). TH is the firstenzyme in dopamine (DA) biosynthesis and catalyses the conversion of L-tyrosineto L-DOPA. We use it to quantify neuron loss in SN and analyze striataldopamine depletions. On postnatal day 60 (D= 0) rats were injected with6-hydroxydopamine (6-OHDA) or vehicle (V) in the left CPu. From D 7-17 (10days), they received a chronic treatment with 17ß- Estradiol (E= 0.1 μg/kg/days.c.) or corn oil (O). Groups were conformed as HP (6-OHDA lesion, O treatmentn= 18); HP+E (6-OHDA lesión, E treatment n= 18); E (V lesion, E treatment n= 15);C (V lesion, O treatment n= 15). On day 60 all animals were euthanized for THIHQ. CICUAL approval 86/2016. In SN, the number of TH+ cells (NN) on bothhemispheres was statistically lower in HP animals in comparison to the othergroups (C= 26 ± 1.4, E= 29.8 ± 3.7, HP= 12.5 ± 1.1, HPE= 28.7 ± 2.3;p<0.0001). To calculate the size of the lesion (SL) we used NN mean valueson both hemispheres and compared the mean difference to control group. Therewas a significant increase in HP group compared to C (mean diff= 13.60,p<0.001). This represents an expansion of the 18.2 % in the size of lesion.In the case of E (mean diff= -3.7) and HP+E (mean diff= -2.6) there was nostatistical difference between means in comparison to C, but the SL wasdiminished in 18.4 % for E and 19.7 % for HPE group. We made a plugin toautomatically count and label TH+ neurons in SN, using this approach wecalculated regression analysis of NN vs. stained area (mm2). Results indicate alinear and positive relation for all groups; goodness of fit (r2) for C was0.54 and perfect (r2= 1) for E, HP and HP+E. Linear regression analysis showsthat, NN is a good predictor for the stained area proportion. What is more,treatment with E improved CPu dopaminergic projections and neuron arborization.Staining was more intense and better distributed in HPE group compared to HP.While 6-OHDA administration diminishes NN and increases lesioned size in HP;evidence shows that E administration attenuates loss and almost reverts tissuedetrimental effects in HPE group. In conclusion, E has neuroprotective effectson the nigrostriatal dopaminergic pathway which may stimulate dopaminesynthesis.@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073786111 1 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;}div.WordSection1{page:WordSection1;}