Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice

Area of Science:

• Neuroscience
• Alzheimer's Disease Research
• Neurobiology

Background:

• The cholinotrophic system is crucial for neuronal survival and is vulnerable in Alzheimer's disease (AD).
• The impact of amyloid plaques and neurofibrillary tangles on this system in AD remains poorly understood.
• Existing AD models often over-express amyloid precursor protein (APP), limiting insights into specific pathologies.

Purpose of the Study:

• To investigate the age- and gender-dependent alterations in the cholinotrophic system of triple transgenic (3xTg)-AD mice.
• To correlate these changes with amyloid plaque and neurofibrillary tangle pathology in the 3xTg-AD model.
• To characterize the cholinotrophic system in relation to Alzheimer's disease hallmarks.

Main Methods:

• Morphological and biochemical characterization of the cholinotrophic system in 3xTg-AD mice at different ages (young, middle-aged, old).
• Stereological analysis of choline acetyltransferase (ChAT)-positive cells.
• Measurement of ChAT enzyme activity, proNGF, TrkA, and p75(NTR) protein levels.

Main Results:

• Cholinergic neuritic swellings increased with age, more in females than males, particularly in the hippocampus.
• A reduction in ChAT-positive cells was observed in the medial septum/diagonal band of aged 3xTg-AD mice.
• ChAT activity decreased in middle-aged 3xTg-AD mice; proNGF increased and TrkA decreased in aged mice (gender-dependent).
• p75(NTR) levels increased in the hippocampus of aged 3xTg-AD mice.

Conclusions:

• Cholinotrophic system alterations in 3xTg-AD mice are age- and gender-dependent.
• These changes are more pronounced in the hippocampus, correlating with Aβ plaque pathology.
• The study provides insights into the development of cholinergic deficits in a relevant AD animal model.