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Alzheimer’s disease (AD) is a neurodegenerative disease that deteriorates cognitive functions and associated brain regions such as the hippocampus, being the primary cause of dementia. Serotonin (5-HT) is widely present in the hippocampus, being an important neurotransmitter involved in learning and memory. Although recent evidence suggests alterations in 5-HT neurotransmission in AD, it is not clear how hippocampal 5-HT innervation is modified. Here, we studied hippocampal 5-HT innervation by analysing: (i) the expression, density and distribution of 5-HT transporter (SERT)-immunoreactive fibres; (ii) the specific morphological characteristics of serotonergic fibres and their relation to amyloid plaques; and (iii) the total number of 5-HT neurons within the raphe nuclei in triple transgenic mouse model of AD. We used quantitative light microscopy immunohistochemistry comparing transgenic and non-transgenic animals of different ages (3, 6, 9, 12 and 18 months). The transgenic animals showed a significant increase in SERT fibres in the hippocampus in a subfield-, strata- and age-specific manner. The increase in SERT fibres was specific to the CA1 stratum lacunosum-moleculare. An increase in SERT fibres in transgenic animals was observed at 3 months (by 61%) and at 18 months (by 74%). No changes, however, were found in the total number of raphe 5-HT neurons at any age. Our results indicate that triple transgenic mice display changes in the expression of SERT and increased SERT fibres sprouting, which may account for imbalanced serotonergic neurotransmission associated with (or linked to) AD cognitive impairment. [ABSTRACT FROM AUTHOR]

Astrocytes, the most numerous cells in the brain, weave the canvas of the grey matter and act as the main element of the homoeostatic system of the brain. They shape the microarchitecture of the brain, form neuronal-glial-vascular units, regulate the blood–brain barrier, control microenvirionment of the central nervous system and defend nervous system against multitude of insults. Here, we overview the pathological potential of astroglia in various forms of dementias, and hypothesise that both atrophy of astroglia and reactive hypertrophic astrogliosis may develop in parallel during neurodegenerative processes resulting in dementia. We also show that in the transgenic model of Alzheimer's disease, reactive hypertrophic astrocytes surround the neuritic plaques, whereas throughout the brain parenchyma astroglial cells undergo atrophy. Astroglial atrophy may account for early changes in synaptic plasticity and cognitive impairments, which develop before gross neurodegenerative alterations.Cell Death and Differentiation (2009) 16, 378–385; doi:10.1038/cdd.2008.172; published online 5 December 2008 [ABSTRACT FROM AUTHOR]