Responses in the aged rat brain after total immunolesion

Area of Science:

• Neuroscience
• Aging Research
• Molecular Biology

Background:

• Cholinergic basal forebrain neurons (CBFNs) are crucial for cognitive functions.
• Nerve growth factor (NGF) plays a vital role in neuronal survival and function.
• Age-related changes can affect neuronal plasticity and neurotrophic factor responses.

Purpose of the Study:

• To compare the effects of cholinergic deafferentation on NGF levels in young and aged rats.
• To investigate glial responses to immunolesions in aged rat brains.
• To assess the impact of cholinergic lesions on NGF and BDNF mRNA levels.

Main Methods:

• Intraventricular injection of the immunotoxin 192 IgG-saporin to induce cholinergic lesions.
• Measurement of choline acetyltransferase (ChAT) activity.
• Quantification of NGF and BDNF mRNA and protein levels.
• Immunohistochemical analysis of AChE-, p75NTR-positive cells, microglia, and astrocytes.

Main Results:

• Cholinergic deafferentation significantly decreased ChAT activity in both young and aged rats, with a more pronounced effect in young rats.
• NGF protein levels increased in the hippocampus, cortex, and olfactory bulb of young rats post-lesion, but not in aged rats (except for minor increases in the olfactory bulb).
• Immunolesions induced a microglial but not astrocytic response in the basal forebrain of aged rats.

Conclusions:

• The immunotoxin 192 IgG-saporin effectively created cholinergic lesions in both young and aged rats.
• The lesion-induced NGF response is partially diminished in aged rat brains.
• Immunolesions trigger a microglial response in aged brains, suggesting an inflammatory component.