<i>Vitamin</i>D<sub>3</sub>Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor-Cognitive Function in -D<sub>2</sub>R Parkinsonian Mice Model

• 作者: Amin Abdulbasit Ansa E. Cobham Azeez O. Ishola Babafemi J. Laoye Damilola E. Oyeleke Ibukun D. Akinrinade Mujittapha U. Sirjao Olalekan M. Ogundele Oluwamolakun O. Bankole Wasiu G. Balogun
• 来源期刊: 生物医学工程(英文)
• 学科: 医学
• 关键词: DOPAMINE Calcium Signalling D2R VD3R CORTICOSTRIATAL Neural System
• 年，卷（期）: swyxgcyw_2015,（9）
• 页码范围: 601-615
• 页数: 15页
• 分类号: R73

摘要

Background: fourth generation antipsychotics have been implicated in the blockade of calcium signalling through inhibition of dopamine receptive sites on dopaminergic D2 Receptor (D3R). As a result of the abnormal calcium signalling associated with D2R inhibition, changes occur in the motor and memory neural axis leading to the observed behavioural deficits after prolonged haloperidol. Thus, Vitamin D3 receptor (VD3R), a calcium controlling receptor in the striatum can be targeted to relief the neurological symptoms associated with haloperidol (-D2R) induced PD. Aim: This study sets to investigate the role of VD3R activation in vitro and in vivo after haloperidol-induced Dopaminergic (D2R) blockade. In addition, we examined the associated neural activity and behavioural changes in parkinsonian and VDRA intervention mice. Methods: Dopaminergic D2R inhibition was investigated in vitro using Melanocytes isolated from the scale of a Tilapia. In four separate set ups, the cells were cultured in calcium free Ringer’s solution as follows;300 μM haloperidol, 100 μM VD3, 100 mM calcium chloride and a combination of 300 μM haloperidol and 100 μM VD3. Subsequently, dopaminergic vesicle accumulation and calcium signalling were observed in bright field microscopy using blue and green fluorescence probes. In the second phase, PD was induced in adult BALB/c mice (-D2;n = 8) after 14 days of intraperitoneal haloperidol treatment (10 mg/Kg). A set of n = 4 mice were untreated (-D2) while the other group (n = 4) received 100 mg/Kg of VD3 for 7 days (-D2/+VDR). The control groups (n = 4 each) were treated with normal saline (NS) and VD3 (+VDR) for 14 days. At the end of the treatment phase, the animals were assessed in Rotarod, parallel bar-, cylinder-, Y-Maze-, one trial place recognition- and novel object recognition-(NOR) tests. Neural activity was measured using chronic electrode implants placed in the M1 (motor cortex), CPu (striatum), CA1 (hippocampus) and PFC (prefrontal cortex). Neural activity was compared with the o