Pro-inflammatory cytokines modify neuronal nicotinic acetylcholine receptor assembly.

We have examined the impact of the inflammatory cytokines interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) on assembly of nAChRs from subunit mixtures of nAChRalpha4, beta2 and beta4 transiently transfected into 293 cells. In control transfections approximately 55% of alpha4 associated preferentially with beta4, but less than 15% complexed with beta2 and the remainder was associated with both beta subunits. These relative ratios were modified by pro-inflammatory cytokines.

Mouse strain-specific changes in nicotinic receptor expression with age.

The onset and severity of age-related loss of neuronal nicotinic acetylcholine receptor (nAChR) expression in the mammalian hippocampus can vary considerably between individuals. We have examined the expression of four nAChR subunits (nAChR alpha4, nAChR alpha5, nAChR alpha7 and nAChR beta4) in the dorsal hippocampus of adult (12-14 months) and aged (24-28 month) animals from two-mouse strains (CBA/J and C57BL/6). The expression of nAChR alpha4 was selectively diminished with age in both strains, and there was a significant loss of nAChR alpha7 in CA1 of aged CBA/J, but not C57BL/6.

Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPAR gamma expression and is altered by long-term NS398 administration.

Age-related changes in the mammalian dorsal hippocampus are associated with diminished expression of neuronal nicotinic acetylcholine receptors (nAChR), which is particularly severe in pathologies such as those associated with dementias, including Alzheimer's disease. Because the mouse is a useful model for age-related decline in nAChR expression in the basal forebrain and limbic system, we used immunohistochemistry to examine the influence of long-term (12-month) oral administration of nicotine and/or the cyclooxygenase-2 (COX-2) preferring non-steroidal anti-inflammatory drug (NSAID) NS398 on nAChR alpha4, alpha5, alpha7, and beta4 expression in the C57BL/6 mouse. Inhibitory neurons of the dorsal hippocampus that express nAChRs also constitutively express COX-2 and the peroxisome proliferator-antagonist receptor subtype gamma-2 (PPAR gamma2) which is also a target of NS398.

Mouse strain-specific nicotinic acetylcholine receptor expression by inhibitory interneurons and astrocytes in the dorsal hippocampus.

The response by individuals to nicotine is likely to reflect the interaction of this compound with target nAChRs. However, resolving how different genetic backgrounds contribute to unique mouse strain-specific responses to this compound remains an important and unresolved issue. To examine this question in detail, expression of the nicotine acetylcholine receptor (nAChR) subunits alpha3, alpha4, alpha5, alpha7, beta2, and beta4 was measured in the dorsal hippocampus using immunohistochemistry in mouse strains or lines BALB/c, C3H/J, C57BL/6, CBA/J, DBA/2, Long Sleep (LS), Short Sleep (SS), and CF1.

Neuronal and astrocyte expression of nicotinic receptor subunit beta4 in the adult mouse brain.

Neuronal nicotinic acetylcholine receptor (nAChR) expression and function are customized in different brain regions through assembling receptors from closely related but genetically distinct subunits. Immunohistochemical analysis of one of these subunits, nAChRbeta4, in the mouse brain suggests an extensive and potentially diverse role for this subunit in both excitatory and inhibitory neurotransmission. Prominent immunostaining included: 1) the medial habenula, efferents composing the fasciculus retroflexus, and the interpeduncular nucleus; 2) nuclei and ascending tracts of the auditory system inclusive of the medial geniculate; 3) the sensory cortex barrel field and cell bodies of the ventral thalamic nucleus; 4) olfactory-associated structures and the piriform cortex; and 5) sensory and motor trigeminal nuclei.