EFFECTS OF DEEP BRAIN STIMULATION OF THE NUCLEUS BASALIS MAGNOCELLULARIS ON MEMORY FUNCTION IN THE D-GALACTOSE INDUCED RAT MODEL OF AGING

Deep brain stimulation (DBS) is a well-established treatment strategy for patients with age-related cognitive disorders. It is currently unknown, which of brain targets is most effective or how chronic stimulation impacts neurocellular and circuit function. Recently, nucleus basalis magnocellularis (NBM) - the major source of cholinergic fibers to the cerebral cortex was explored as a potential target for deep brain stimulation (DBS) in patients with dementia; some studies reporting improvement in cognitive dysfunction following NBM-DBS. Given that aging is to some extent associated with cholinergic deficits and that pro-cholinergic treatment improves cognitive functions, in the present study, we investigated whether unilateral NBM-DBS improves age-related memory impairment in a D-galactose (D-gal) induced rat model of aging, in parallel with changes in cholinergic markers in the NBM and medial prefrontal cortex (mPFC). Male outbred albino rats – aged 3 months served as subjects at the start of experimentation. Rats were randomly assigned to prepare experimental groups: control; D-gal - with chronic administration (8 weeks) of D-gal; D-gal/I - with electrode implantation; D-gal/S - with electrical stimulation. The results indicate that D-gal administration causes deficits in memory function, a decrease in the number of acetylcholinesterase-immunoreactive neurons in the mPFC and choline acetyltransferase-immunoreactive neurons in the NBM. NBM-DBS improves memory function and increases the number of acetylcholinesterase-immunoreactive neurons in the mPFC. In summary, it can be concluded that NBM-DBS improves memory impairment by modulating cholinergic neurotransmission in the mPFC in a rat model of aging.
Supported by the funding from the SRNSFG: Grant #-FR-23-18847