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Chronic basal forebrain activation improves spatial memory, boosts neurotrophin receptor expression, and lowers BACE1 and Aß42 levels in the cerebral cortex in mice.
Kumro, Jacob; Tripathi, Ashutosh; Lei, Yun; Sword, Jeremy; Callahan, Patrick; Terry, Alvin; Lu, Xin-Yun; Kirov, Sergei A; Pillai, Anilkumar; Blake, David T.
Affiliation
  • Kumro J; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Tripathi A; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77054, United States.
  • Lei Y; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Sword J; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Callahan P; Department of Pharmacology/Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Terry A; Department of Pharmacology/Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Lu XY; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Kirov SA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
  • Pillai A; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77054, United States.
  • Blake DT; Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
Cereb Cortex ; 33(12): 7627-7641, 2023 06 08.
Article in En | MEDLINE | ID: mdl-36939283
ABSTRACT
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 Aß42 in 5xFAD mice. These data support a causal relationship between basal forebrain activation and both neurotrophin activation and reduced Aß42 generation and accumulation. The observation that basal forebrain activation suppresses Aß42 accumulation, combined with the known high-affinity antagonism of nicotinic receptors by Aß42, documents bidirectional antagonism between acetylcholine and Aß42.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease / Basal Forebrain Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cereb Cortex Journal subject: CEREBRO Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease / Basal Forebrain Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cereb Cortex Journal subject: CEREBRO Year: 2023 Document type: Article Affiliation country: