Premium
[P3–046]: NOVEL NON‐CATECHOL D1 RECEPTOR AGONISTS EXHIBIT SUSTAINED PHARMACOLOGICAL ACTIVITY
Author(s) -
Tierney Patrick L.,
Allen John A.,
Volfson Dmitri,
Lotarski Susan,
Rossi Amie,
Gray David L.,
Kozak Rouba
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1859
Subject(s) - agonist , tachyphylaxis , quinpirole , pharmacology , chemistry , dopamine agonist , in vivo , dopamine , desensitization (medicine) , endocrinology , receptor , partial agonist , medicine , biology , biochemistry , microbiology and biotechnology
Background: Sleep deprivation (SD) has been implicated as a risk factor for various neurodegenerative disorders viz., dementia including Alzheimer’s disease, ultimately leading to cognitive impairment. It has enduring effects on learning and memory, besides hippocampal synaptic plasticity. Although SD is known to result in cognitive impairment, mechanisms underlying this process are still not clear. Angiotensin converting enzyme (ACE) inhibitors has been studied for its neuroprotective effect against Parkinson’s, Alzheimer’s, Cerebral stroke etc., Hence we investigated the effects of Captopril, the first generation drug of ACE inhibitors on sleep deprivation induced cognitive impairment in C57BL/6J mice. Methods: We used Single platform method of Sleep deprivation in C57BL/6J mice for continuous 5 days. Novel object recognition test (NORT) and elevated plus maze (EPM) were used to assess the cognitive enhancing effect of Captopril during SD. Hippocampal synaptic plasticity was investigated using pre and post – synaptic markers such as Synapsin – I and Neurabin. Brain derived neurotrophic factor (BDNF), which is known to play critical role in synaptic transmission was also examined, besides NeuN. Spine density was evaluated by Golgi method and ultra-structural alterations in the hippocampus were studied by Transmission electron microscopy (TEM). Results: SD caused structural and functional alterations in brain that led to severe learning and memory impairment. Mice treated with Captopril during SD, significantly (p<0.01) improved recognition and spatial memory. The Immunohistochemical staining showed decreased expressions of Synapsin I and Neurabin in SD group whereas Captopril treatment exhibited significant (p<0.001) increase of these expressions in the hippocampus tissue. Treatment with Captopril showed substantial (p<0.01) upregulation in the BDNF expression compared to that of SD group which was accompanied by increased number of NeuN positive cells in the treatment group. Similarly the decreased spine density in SD group was moderately restored by Captopril, besides considerable degree of restoration of the hippocampal mitochondria structure revealed by TEM. Conclusions: Results of the present studies for the first time reports that Captopril attenuates sleep deprivation induced cognitive dysfunction bymodulating the synaptic plasticity, thereby improving the learning and memory functions.