V. Haroutunian

Attenuation of nucleus basalis of Meynert lesion-induced cholinergic deficits by nerve growth factor

Nerve growth factor (NGF) was administered into either the lateral ventricle or into the basal forebrain of n. basalis of Meynert (nbM) lesioned rats. Rats received either continuous infusion of 5 micrograms of 7S NGF per day for 28 days, or 5 micrograms of 7S NGF on 4 occasions distributed evenly during the first two post-lesion weeks. The administration of NGF reduced lesion-induced cortical cholinergic marker deficits by approximately 50%, irrespective of the locus or mode of NGF administration. Thus NGF is able to attenuate lesion-induced cholinergic deficits across a range of treatment and lesion conditions.

Interactions of forebrain cholinergic and somatostinergic systems in the rat

The neurochemical, behavioral and pharmacological effects of forebrain cholinergic and somatostatinergic deficits were assessed in adult rats. Brain somatostatinergic activity was manipulated by the systemic administration of different doses of cysteamine. Forebrain cholinergic systems were lesioned by the infusion of ibotenic acid into the nucleus basalis of Meynert (nbM). Forebrain cholinergic lesions did not affect forebrain somatostatin-like-immunoreactivity (SLI). Depletion of forebrain SLI by cysteamine did not significantly affect forebrain cholinergic marker activity. The combination of forebrain cholinergic deficits with forebrain somatostatinergic deficits did not lead to any greater impairment of mnemonic function than that produced by lesions alone, nor did SLI deficits hamper the efficacy of physostigmine to enhance memory in sham operated or nbM-lesioned rats. These results suggest that although forebrain cholinergic and somatostatinergic systems do interact at some levels, this interaction is a minor one with respect to neurochemical, behavioral or pharmacological variables.

Functional muscarinic supersensitivity in denervated rat hippocampus

The effects of carbachol (CCh), a cholinergic agonist, were compared in voltage-clamped hippocampal pyramidal neurons in vitro, obtained from normal and fimbria-fornix-lesioned rats. A substantial increase in sensitivity to the effects of CCh was seen in denervated neurons. The supersensitivity was demonstrated on both the inward leak current and the calcium-dependent potassium current, IAHP. These findings provide convincing evidence for cholinergic denervation supersensitivity in the hippocampus.

Cholinergic marker deficits induced by lesions of the nucleus basalis of Meynert are attenuated by nerve growth factor in young, but not in aged, F344 rats

To investigate the efficacy of nerve growth factor (NGF) in promoting recovery from cholinergic damage, young (3-4 month old) and aged (22-23 month old) Fischer 344 rats received NMDA-induced unilateral lesions of the nucleus basalis of Meynert and subcutaneous osmotic pumps (2-week duration) connected to permanently implanted cannulas directed at the lateral ventricle ipsilateral to the lesion. Pumps were filled with either artificial CSF/rat serum albumin (the vehicle) or 5.0 micrograms of angiotensin-free, beta-NGF. Fourteen days after surgery, all subjects were sacrificed and their brains regionally dissected (frontal and occipital cortices, striatum, and dorsal and ventral hippocampi) and assayed for choline acetyltransferase (CAT) and acetylcholinesterase (AChE). Results indicated that the lesion decreased CAT and AChE levels within the frontal cortex of both young (29.8% and 39.4% depletion, respectively) and aged (30.5% and 34.8% depletion, respectively) animals. Only in young animals did NGF reduce these lesion-induced CAT (by 34.2%) and AChE deficits (by 65.5%). In fact, NGF exacerbated frontal cortical CAT depletions in aged animals in that percent depletion was 11.3% more following treatment (30.5% vs. 41.8% depletion in Aged/CSF and Aged/NGF groups, respectively). Lower CAT and AChE levels were found in the striatum of aged animals, an effect not reversed by NGF treatment. In contrast, NGF in young animals enhanced striatal CAT activity on the non-lesioned side by 22.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Inositol levels in post mortem brain samples of Alzheimer's patients

Abstract 1. 1. Free inositol levels in occipital and parietal cortex of Alzheimers Disease (AD) patients were reported to be significantly elevated by 10–35% compared with matched controls, studied by magnetic resonance spectroscopy (MRS) during life. 2. 2. An MRS study of post mortem samples failed to demonstrate a significant difference between AD and controls. 3. 3. The present study shows non-significant trends of 13% increase in frontal cortex and 5% and 21% decrease in occipital cortex and cerebellum respectively, in post mortem brain specimens of AD patients measured gas chromatographically (GC).