The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-10-01 DOI:10.1016/j.jchemneu.2023.102317
Luis Ángel Lima-Castañeda , María Elena Bringas , Leonardo Aguilar-Hernandez , Linda Garcés-Ramírez , Julio César Morales-Medina , Gonzalo Flores
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Abstract

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

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抗精神病药奥氮平可减少自闭症雄性大鼠模型的记忆缺陷和神经元异常
自闭症谱系障碍(ASD)是一种影响社会互动和感觉处理的神经发育疾病,其患病率正在上升。怀孕期间暴露于丙戊酸(VPA)会导致后代出现自闭症样特征。奥氮平(OLZ)是一种非典型抗精神病药物,用于治疗ASD。我们通过产前VPA治疗评估了OLZ对大鼠行为、神经形态和海马一氧化氮(NO)水平的影响。众所周知,ASD患者表现出感觉异常。因此,我们利用甩尾测试来验证ASD模型。在新目标识别测试(NORT)中,VPA暴露降低了首次引入新目标时的识别指数(DI)。此外,OLZ和给药的大鼠在第二次接触新物体的DI时表现不同,这表明OLZ逆转了vpa诱导的识别记忆缺陷。在给药后,vpa暴露大鼠的Morris水迷宫记忆和学习测试中发现隐藏平台的潜伏期有所提高,表明OLZ改善了这些大鼠的空间记忆。产前给药VPA可诱导海马CA1区锥体神经元的神经元萎缩和脊柱密度降低。OLZ治疗可纠正VPA引起的神经形态学改变。在海马CA1区,VPA处理增加了神经元数量,OLZ处理使其正常化。OLZ使对照大鼠海马背侧一氧化氮水平升高。在暴露于VPA的大鼠中,第二代抗精神病药OLZ可减少记忆相关和神经可塑性改变。目前的研究结果支持在这种疾病中使用OLZ,并进一步验证了产前VPA作为ASD模型的使用。
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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
期刊最新文献
Editorial Board Retraction notice to “Astrocyte response to melatonin treatment in rats under high-carbohydrate high-fat diet” [J. Chem. Neuroanat. 136 (2024) 102389] Retraction notice to “Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol” [J. Chem. Neuroanat. 135 (2024) 102367] Retraction notice to “Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus” [J. Chem. Neuroanat. 114(2021) 101946] Retraction notice to “Aqueous leaf extract of Phyllanthus amarus protects against oxidative stress and misfiring of dopaminergic neurons in Paraquat-induced Parkinson's disease-like model of adult Wistar rats” [J. Chem. Neuroanat. 135 (2024) 102365]
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