Effect of ipsilateral lesioning of the nucleus basalis magnocellularis and of L-alpha-glyceryl phosphorylcholine treatment on choline acetyltransferase and acetylcholinesterase in the rat fronto-parietal cortex.
ABSTRACT The present study assesses the effect of unilateral lesions of the nucleus basalis magnocellularis (NBM) and of treatment with L-alpha-glyceryl phosphorylcholine (GFC, choline alfoscerate) on the acetylcholine-synthesizing (choline acetyltransferase (ChAT)), and acetylcholine-degradating (acetylcholinesterase (AChE)) enzymes in the rat fronto-parietal cortex ipsilateral to the lesion. Ibotenic acid injections in the right NBM area caused a significant decrease of both ChAT and AChE activities as well as of histochemically reactive stores of AChE in the right fronto-parietal cortex. Treatment with GFC restored in part the loss of ChAT and AChE activities. Moreover, AChE reactivity is restored in the fronto-parietal cortex of NBM-lesioned rats treated with GFC. GFC is a precursor in the biosynthesis of brain phospholipids which increases the bioavailability of acetylcholine in the nervous tissue. The possible relevance of the restoration of the marker enzymes of cholinergic neurotransmission by GFC in an animal model of cholinergic hypofunction is considered.
- [show abstract] [hide abstract]
ABSTRACT: The effect of 4 and 8 weeks of treatment with the thyrotropin releasing hormone (TRH), analogue posatirelin (L-6-ketopiperidine-2-carbonyl-L-leucyl-proline amide), on the changes of cholinergic neurotransmission enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), caused by lesions of the nucleus basalis magnocellularis (NBM), was investigated in the rat frontal cortex. ChAT and AChE were demonstrated with immunohistochemical and histochemical techniques, respectively associated with image analysis and microdensitometry. Monolateral and bilateral lesions of NBM area caused a significant loss of ChAT-immunoreactive nerve cell bodies in the NBM, as well as a remarkable decrease of ChAT-immunoreactive fibres and of AChE reactivity in the frontal cortex ipsilateral to the lesion or of both sides, respectively. The number of ChAT-immunoreactive nerve cell bodies in the lesioned NBM was higher in posatirelin-treated rats for 8 weeks in comparison with control NBM-lesioned rats. Moreover, the compound increased the number of ChAT-immunoreactive fibres in the frontal cortex of monolaterally and bilaterally NBM-lesioned rats at 8 weeks after lesion, but was without effect on these fibres in sham-operated rats. The same is true for AChE reactivity, developed in the neuropil of the frontal cortex, which was restored in part by an 8-week treatment with posatirelin in NBM-lesioned rats. These findings suggest that treatment with posatirelin rescues cholinergic neurons of the NBM and cholinergic projections to the cerebral cortex affected by lesioning of the NBM. The functional relevance of these observations and their possible applications should be evaluated in future studies.Mechanisms of Ageing and Development 09/1998; 104(2):183-94. · 3.26 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Brain levels of glycerophosphodiesters, including glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), are altered in many human central nervous system disorders. Although much information is available on the enzymes responsible for the formation of these phospholipid metabolites, little information is known regarding their catabolism, by glycerophosphodiesterases, in human brain. In both autopsied and biopsied temporal cortex, a phosphocholine-producing glycerophosphodiesterase activity was observed. In the presence of 1 mM EDTA, the enzyme possessed a pH optimum of 9.0, while the addition of 5 mM zinc acetate shifted the pH optimum to 10.5. When assayed at pH 9.0 in the absence of zinc acetate, the Km and Vmax were 104 +/- 2 microM and 77 +/- 18 nmol/h/mg protein, respectively, while assaying at pH 10.5 in the presence of 5mM zinc acetate yielded a Km of 964 +/- 56 microM, and a Vmax of 534 +/- 114 nmol/h/mg protein. Furthermore, whereas submillimolar concentrations of zinc acetate stimulated the activity of the enzyme in a dose-dependent manner when assayed at pH 10.5 (EC50 =20.3 +/- 3.0 microM), this did not result in a reciprocal inhibition of glycerophosphocholine phosphodiesterase (GPC PD) activity when assayed at a more acidic pH. This may suggest that human brain contains two phosphocholine-producing GPC PD activities, differentiable by their sensitivity to zinc ions. An activity capable of hydrolyzing GPE to form phosphoethanolamine could not be detected in either biopsied or autopsied brain. However, a choline/ethanolamine-producing glycerophosphodiesterase activity could be readily detected in biopsied, but not autopsied brain. this novel enzyme possessed a neutral pH optimum and was dependent upon divalent cations for activity. In conclusion, human brain contains at least two different glycerophosphodiesterases, a phosphocholine, and a choline/ethanolamine-producing activity, only one of which can be detected in autopsied tissue. The results of previous studies measuring brain glycerophosphodiesterase activity in degenerative brain conditions may need to be reevaluated in the light of these observations.Lipids 01/1996; 30(12):1075-81. · 2.56 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Substantial evidence suggests a role for nutrition in the management of AD and especially suggests that interventions with combinations of nutrients are more effective than single-nutrient interventions. The specific multi-nutrient combination Fortasyn™Connect (FC), shown to improve memory in AD, provides phosphatide precursors and cofactors and is designed to stimulate the formation of phospholipids, neuronal membranes, and synapses. The composition comprises nucleotides, omega-3 polyunsaturated fatty acids (n3 PUFA), choline, B-vitamins, phospholipids, and antioxidants. The current study explored the protective properties of FC in a membrane toxicity model of AD, the amyloid-β 1-42 (Aβ42) infused rat, which shows reduced exploratory behavior in an Open Field and impaired cholinergic functioning. To this end, rats were fed an FC enriched diet or a control diet and five weeks later infused with vehicle or Aβ42 into the lateral ventricle. Ten weeks post-infusion Aβ42-rats fed the FC diet showed increased membrane n3 PUFA and phosphatidylcholine content while they did not show the reductions in exploratory behavior or in choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunoreactivity that were seen in Aβ42-rats fed the control diet. We conclude that FC protects the cholinergic system against Aβ42-induced toxicity and speculate that the effects of FC on membrane formation and composition might be supportive for this protective effect. Based on these data a long-term intervention study was started in the prodromal stages of AD (NTR1705, LipiDiDiet, EU FP7).Journal of Alzheimer's disease: JAD 08/2011; 27(2):327-39. · 4.17 Impact Factor