How does neurokinin 3 receptor agonism affect pathological and cognitive impairments in an Alzheimer's disease-like rat model?

Alzheimer's disease (AD) is accepted as a form of progressive dementia. Cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning memory-related processes. It is known that the activation of NK3R affects the release of many neurotransmitters. The aim of this project was to investigate the effects of NK3R agonist senktide administration on neurobehavioral mechanisms in the experimental AD-like rat model. 50 male Wistar albino rats were divided into Control (C), AD, Control + NK3R agonist (CS), AD + NK3R agonist (ADS), AD + NK3Ragonist + antagonist groups (ADSO). We designed AD-like model by intrahippocampal administration of Aβ1-42. After NK3R agonist + antagonist injections, open field (OF), Morris water maze (MWM) tests were applied. Cholinergic mechanism analysis from hippocampus-cortex tissues was performed by ELISA and catecholamine analysis from brain stem tissue were performed by HPLC method. The transitions from edge to center, rearing, grooming parameters were found to be reduced in final values of OF. While the group-time interaction was significant in the OF test findings, there was no significant difference between the groups. In MWM test, ADS group showed a learning level close to control group and animals in AD and ADSO groups could not learn target quadrant in MWM test. The brain stem NA and DA concentrations were not statistically significant. Hippocampal AChE-ChAT levels were supported by positive effects of senktide on learning via the cholinergic mechanisms. As a result, NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. In the experimental AD model, positive effects of NK3R on learning memory may be mediated by cholinergic mechanisms.