Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico; Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional (IPN), CDMX, Mexico.
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico.
J Chem Neuroanat. 2022 Mar;120:102061. doi: 10.1016/j.jchemneu.2021.102061. Epub 2021 Dec 22.
Hypertension is a risk factor for vascular dementia, which is the second most prevalent type of dementia, just behind Alzheimer's disease. This highlights the brain vulnerability due to hypertension, which may increase with aging. Thus, studying how hypertension affects neural cells and behavior, as well as the effects of antihypertensives on these alterations, it's important to understand the hypertension consequences in the brain. The spontaneously hypertensive rat (SHR) has been useful for the study of hypertension alterations in diverse organs, including the brain. Thus, we studied the losartan effects on cognitive and structural neuroplasticity impairments in SHR of 10 months of age. In the first instance, we evaluated the losartan effects on exploratory behavior and novel object recognition test (NORT) in the SHR. Then, we assessed the density and morphology of dendritic spines of pyramidal neurons from the prefrontal cortex (PFC) layers 3 and 5, and CA1 of the dorsal Hp (dHp). Our results indicate that in SHR, losartan treatment (2 months, 15 mg/Kg/day) reduces high blood pressure to age-matched vehicle-treated Wistar-Kyoto (WKY) rat levels. Moreover, losartan improved long-term memory in SHR compared with age-matched vehicle-treated WKY rats, without affecting the locomotor and anxiety behaviors. The behavioral improvement of the SHR can be associated with the increase in the number of dendritic spines and the mushroom spine population in the PFC and the dHp. In conclusion, losartan enhances cognitive impairments by controlling the high blood pressure and improving neuroplasticity in animals with chronic hypertension.
高血压是血管性痴呆的一个风险因素，血管性痴呆是仅次于阿尔茨海默病的第二大常见痴呆症。这凸显了高血压对大脑的脆弱性，而这种脆弱性可能随着年龄的增长而增加。因此，研究高血压如何影响神经细胞和行为，以及抗高血压药物对这些改变的影响，对于了解高血压对大脑的后果非常重要。自发性高血压大鼠（SHR）已被用于研究包括大脑在内的多种器官的高血压改变。因此，我们研究了洛沙坦对 10 月龄 SHR 认知和结构神经可塑性损伤的影响。首先，我们评估了洛沙坦对 SHR 探索行为和新物体识别测试（NORT）的影响。然后，我们评估了背海马（dHp）CA1 和前额叶皮层（PFC）第 3 和第 5 层的锥体神经元树突棘的密度和形态。我们的结果表明，在 SHR 中，洛沙坦治疗（2 个月，15mg/Kg/天）可将高血压降低至与年龄匹配的 vehicle 治疗的 Wistar-Kyoto（WKY）大鼠水平。此外，与年龄匹配的 vehicle 治疗的 WKY 大鼠相比，洛沙坦改善了 SHR 的长期记忆，而不影响运动和焦虑行为。SHR 的行为改善可能与 PFC 和 dHp 中树突棘数量和蘑菇状树突棘群体的增加有关。总之，洛沙坦通过控制高血压和改善慢性高血压动物的神经可塑性，增强了认知障碍。
