Medical University of Gdansk, Department of Medical Laboratory Diagnostics - Biobank Fahrenheit BBMRI.pl, Debinki Street 7, 80-211 Gdansk, Poland; Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7, 80-211 Gdansk, Poland.
Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 12 Smętna Street, 31-343 Kraków, Poland.
Brain Res. 2021 Oct 1;1768:147577. doi: 10.1016/j.brainres.2021.147577. Epub 2021 Jul 1.
The olfactory bulbectomized (OBX) rat model is a well-established model of depression in which antidepressant drugs reverse deficits in the passive avoidance test 14 days after administration. Recently, the olfactory bulbectomized rat model has been proposed to be a model of Alzheimer's disease (AD), and the available data indicate similarities between the changes that typically occur in AD and those observed in OBX animals. In the present study, the occurrence of neurochemical impairments related to AD were investigated 8 months after OB ablation. The expression of the nitric oxide synthases eNOS and nNOS, receptor for advanced glycation endproducts (RAGEs) and dimethylarginine dimethylaminohydrolase (DDAH1) in the prefrontal cortices (PFCs), hippocampi and striata of olfactory bulbectomized and sham-operated rats was evaluated. Subsequently, the impact of the administration of a positive allosteric modulator of the mGlu receptor, CDPPB (14 days, 2.5 or 5 mg/kg), on OBX-related changes was assessed. OB ablation induced typical deficits in passive avoidance. Significant aberrations in the expression of both isoforms of NOS were observed in the hippocampus and striatum, and the expression of DDAH1 was increased in the PFCs of OBX animals. CDPPB at a dose of 5 mg/kg ameliorated cognitive impairment in the passive avoidance test and partially reversed the changes in eNOS and nNOS expression induced by the lesion. The results of this study confirm that some of the neurochemical changes observed in OBX animals may resemble those associated with AD pathology and that activation of the mGlu receptor may partially counteract these pathological alterations.
嗅球切除术（OBX）大鼠模型是一种成熟的抑郁症模型，抗抑郁药物可在给药 14 天后逆转被动回避测试中的缺陷。最近，嗅球切除术大鼠模型被提出是阿尔茨海默病（AD）的模型，并且现有数据表明通常在 AD 中发生的变化与在 OBX 动物中观察到的变化相似。在本研究中，在 OB 消融后 8 个月研究了与 AD 相关的神经化学损伤的发生。评估了前额叶皮层（PFC）、海马和纹状体中内皮型一氧化氮合酶（eNOS）和神经元型一氧化氮合酶（nNOS）、晚期糖基化终产物受体（RAGEs）和二甲基精氨酸二甲氨基水解酶（DDAH1）的表达。随后，评估了 mGlu 受体正变构调节剂 CDPPB（14 天，2.5 或 5mg/kg）给药对 OBX 相关变化的影响。OB 消融导致被动回避的典型缺陷。在海马体和纹状体中观察到两种NOS 同工型的表达明显异常，并且 OBX 动物的 PFC 中 DDAH1 的表达增加。5mg/kg 的 CDPPB 改善了被动回避测试中的认知障碍，并部分逆转了损伤诱导的 eNOS 和 nNOS 表达变化。本研究的结果证实，在 OBX 动物中观察到的一些神经化学变化可能与 AD 病理学相关，并且 mGlu 受体的激活可能部分抵消这些病理改变。
