de Butte M, Fortin T, Sherren N, Pappas BA (2001) Selective neonatal neurochemical lesions persist into old age and cause Alzheimer-like pathology. Neuroscience 2001 Abstracts 426.8. Society for Neuroscience, San Diego, CA.
Summary: There is a strong negative correlation between forebrain acetylcholine (ACH) function and the depth of Alzheimer’s dementia (AD). Forebrain norepinephrine (NE) is also frequently reduced in AD. However, it is not clear when these neurochemical abnormalities begin. Since there is some evidence to suggest that the AD begins early in life but fulminates with aging, it may also be the case that ACH and/or NE dysfunction occurs early and participates in the slide towards dementia in old age. To shed light on this possibility, we created lesions of forebrain ACH and NE in the neonatal rat by intracranial injection of 192 IgG saporin and systemic injection of 6-OHDA respectively, allowing the animals to reach old age. Massive ACH and NE lesions were evident at 22 months of age as reflected by immunohistochemical probes for p75 low affinity nerve growth factor and dopamine beta hydroxylase immunoreactive axons respectively. Morris water maze testing showed that surprisingly, the NE but not the ACH lesioned rats were impaired on this reference memory task. Typically, young NE lesioned rats are not impaired on it. The ACH lesion did not exacerbate the consequences of the NE lesion. On the other hand, unbiased stereological counts of hippocampal CA1 pyramidal cells indicated that the ACH lesion caused a significant loss of cells whereas the NE lesion had no effect by itself nor did it exacerbate the effects of the ACH lesion. These results indicate that selective NE and ACH lesions inflicted at birth, persist into old age. Furthermore, the NE lesion seemingly impairs memory in old age while the ACH lesion causes a loss of CA1 cells reminiscent of that which is a hallmark of AD.
Related Products: 192-IgG-SAP (Cat. #IT-01)