Center of Experimental Morphology

Departamento de Anatomia - Faculdade de Medicina da Universidade do Porto

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Neurotrophins and Brain

Research Area: Health Sciences
Status: In progress  
Project leaders:  
In cooperation with
  • Faculdade de Medicina - Universidade do Porto


Central cholinergic pathways are ideally suited to regulate global functions that rely upon the cerebral cortex, such as attention, arousal, motivation, memory and consciousness. Taking into account the available information, there are reasons to believe that the cholinergic system may be in a position to mediate changes in the cellular organization and/or in the phenotype of the medial prefrontal cortex (mPFC), nucleus accumbens (Nac) and amygdala neurons.

The mPFC receives cholinergic innervation originating both from the basal forebrain (BF) and brainstem reticular formation. The mPFC has been associated with diverse functions including attention, visceromotor activity, decision making, goal directed behavior and working memory. Our study will focus on vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) producing neurons. The Nac is a central component of the limbic system of the brain. Cholinergic interneurons of the Nac represent less than 1% of local neurons. NPY-containing cells are medium-sized aspiny interneurons. NPY may influence ethanol intake by regulating basal levels of anxiety, and by modulating the sedative effects of ethanol and/or its rewarding properties. The amygdala is located in the medial aspects of the temporal lobe and is implicated in a variety of functions, ranging from attention to memory and emotion. Nucleus basalis magnocellularis (NBM) cholinergic neurons are the major source of cholinergic innervation of the amygdala.

Our first objective is to study the effects of aging on the cholinergic innervation of the brain and to evaluate if the possible changes are mimicked by chronic alcohol consumption, a condition that accelerates brain aging. The second objective is to assess the potential beneficial effects of neurotrophic factors in the aging brain. Therefore, we shall investigate the following groups of male rats: a) young, b) old, c) young submitted to chronic ethanol treatment (CET), d) old submitted to CET, e) young submitted withdrawal (W) from CET, f) young in which the NBM was destroyed, g) young in which the laterodorsal tegmental nucleus (LDT) was destroyed, h) W treated intracerebroventricularly with nerve growth factor (NGF), i) old NGF-treated. The optical fractionator method will be used to estimate the total number of neurons and the optical rotator will be applied to estimate the mean somatic volume of neurons. In the amygdala, we shall analyze the areal densities of NPY and VIP neurons. The study of mPFC cholinergic network will be done using a computer-assisted image analyzer.


We found no significant differences in the total number of cholinergic neurons in the pedunculopontine tegmental nucleus (PPT) of aged rats, which differs from what has been reported to happen in the BF. Thus, the brainstem neurons seem to be more resistant to age-associated degenerative changes than those in the BF.

In the NAc, we found no significant effect of CET and W on the total number of NPY-immunoreactive neurons in adult rats. On contrary, in alcohol-fed aged rats the expression of NPY was reduced to about 33% of the levels in controls. Our data also showed that NGF significantly increases the expression of NPY in the NAc of W rats. We further demonstrated that CET, W and NGF administration do not affect the mean somatic volume of the Nac NPY-producing neurons.

These results demonstrate that aging interfere with the effects of CET in the expression of NPY in the NAc. This study might help to explain the role of NPY in alcohol intake, alcohol dependence and and alcohol withdrawal.


Diana Filipa da Costa Santos (2010) The effects of nerve growth factor upon the neuropeptide Y content of nucleus accumbens of old rats: a stereological study. Master Thesis. Porto Medical School (Supervisor: M. Dulce Madeira).


Gomes, AC, Pereira P. Age does not affect the total number of cholinergic neurons of the pedunculopontine tegmental nucleus of the rat: an unbiased stereological study. V YES Meeting. Porto, Setembro de 2010.

Neves J, Pereira P. Effects of chronic ethanol treatment and withdrawal on the expression of neuropeptide Y in the rat nucleus accumbens: an unbiased stereological study. V YES Meeting. Porto, Setembro de 2010.

Centro de Morfologia Experimental
Faculdade de Medicina da Universidade do Porto
Al. Professor Hernâni Monteiro
4200-319 Porto
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