Expression of mRNA for neurotensin in rat brain cholinergic neurons

Abstract

The tridecapeptide neurotensin (NT) is a putative neurotransmitter in the central nervous system. Studies with experimental animals show that NT interacts with cholinergic neurons. It is proposed that NT is involved in the pathophysiology of some neuropsychiatric disorders thought to be related to malfunction of cholinergic systems. Alzheimer's disease, characterized clinically by a profound loss of memory, is associated with a significant loss of cholinergic neurons in the brain. In the present study, we have compared the distribution of NT/neuromedin N precursor protein ndlNA in rat forebrain to that of choline acetyl transferase (CHAT) immunoreactivity (marker for cholinergic neurons in this region). We used the ABC method for immunohistochemical experiments. We examined the expression of mRNA in the identical brain sections using in situ hybridization techniques. We used an 3sS-labeled antisense RNA probe complementary to the cDNA. In some nuclei of the rat forebrain, mRNAs were highly expressed in the ChAT-immunoreactive neurons. These findings suggest that cholinergic neurons in these areas synthesize neurotensin and express them in their perikarya and probably in the terminal regions of the cholinergic pathways including the amygdala. Deficits in neurotensin as well as in acetylcholine in the amygdala may underlie some of the clinical manifestation of Alzheimer's disease. Our data support the hypothesis that neurotensin plays an important role in the pathophysiology of memory dysfunction in Alzheimer's disease. (Supported by the Mayo Foundation and U.S.P.H.S. Grant MH27692.) and may be related to basal ganglia dysfunction. Irritability is less frequent and may be a behavioral expression of AD patients with poor insight into their cognitive deficits.