| First Author | Kumro J | Year | 2023 |
| Journal | Cereb Cortex | Volume | 33 |
| Issue | 12 | Pages | 7627-7641 |
| PubMed ID | 36939283 | Mgi Jnum | J:350959 |
| Mgi Id | MGI:7663196 | Doi | 10.1093/cercor/bhad066 |
| Citation | Kumro J, et al. (2023) Chronic basal forebrain activation improves spatial memory, boosts neurotrophin receptor expression, and lowers BACE1 and Abeta42 levels in the cerebral cortex in mice. Cereb Cortex 33(12):7627-7641 |
| abstractText | The etiology of Alzheimer's dementia has been hypothesized in terms of basal forebrain cholinergic decline, and in terms of reflecting beta-amyloid neuropathology. To study these different biological elements, we activated the basal forebrain in 5xFAD Alzheimer's model mice and littermates. Mice received 5 months of 1 h per day intermittent stimulation of the basal forebrain, which includes cholinergic projections to the cortical mantle. Then, mice were behaviorally tested followed by tissue analysis. The 5xFAD mice performed worse in water-maze testing than littermates. Stimulated groups learned the water maze better than unstimulated groups. Stimulated groups had 2-3-fold increases in frontal cortex immunoblot measures of the neurotrophin receptors for nerve growth factor and brain-derived neurotrophic factor, and a more than 50% decrease in the expression of amyloid cleavage enzyme BACE1. Stimulation also led to lower Abeta42 in 5xFAD mice. These data support a causal relationship between basal forebrain activation and both neurotrophin activation and reduced Abeta42 generation and accumulation. The observation that basal forebrain activation suppresses Abeta42 accumulation, combined with the known high-affinity antagonism of nicotinic receptors by Abeta42, documents bidirectional antagonism between acetylcholine and Abeta42. |
