Neuroanatomical, neuroimaging and molecular endophenotypes of cognitive disturbances in male rats with accelerated senescence

Tamara Amstislavskaya, Ph.D., D.Sc.


Deputy Director for Science, Head of the Laboratory of Translational Biopsychiatry, Department of Experimental and Clinical Neuroscience, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russian Federation.

Chief Scientist, Department of Neuroscience, Laboratory of Translational and Clinical Neuroscience, Novosibirsk State University, Novosibirsk, Russian Federation.



    Aging is associated with a general decline of physiological functions, and those which depend on the central nervous system are the most affected. Here we studied the olfactory function in aging male rats using fMRI comparing the brain activity in regions involved in perception (olfactory bulbs) and processing (thalamus, hypothalamus, frontal cortex, hippocampus) of sexually or socially significant odor stimulus with 11.7 T MR-scanner and behavioral tests (odor habituation and social recognition) in male rats with normal (Wistar rats) or accelerated senescence (D-galactose-treated Wistar rats or OXYS rats with hereditary defined accelerated aging). BOLD-signal magnitude in the hippocampus was reduced in response to sexually significant stimulus while this parameter was increased in response to socially significant stimulus in Wistar rats chronically treated with D-galactose. Similar alterations were observed in OXYS rats. Time of odor exploration in behavioral tests was increased and neuronal activity in olfactory bulbs in response to both types of stimuli correlated in D-galactose-treated rats indicating possible disturbances in odor discrimination. However, olfactory threshold was not changed since the BOLD-signal magnitude in the olfactory bulbs in response to the same concentration of odor did not vary significantly between rats with normal and accelerated senescence. Our results evidence that accelerated senescence is associated with profound disturbances at the level of processing the olfactory information in the hippocampus. Signs of altered odor discrimination in the olfactory bulbs and augmented time of odor exploration may evidence that disturbances in odor perception in the olfactory bulbs are also involved in aging-related dysfunction.