Preserved cerebellar tyrosine hydroxylase-immunoreactive neuronal fibers in a behaviorally aggressive subgroup of Alzheimer's disease patients

Russo-Neustadt, Amelia; Zomorodian, Toska J.; Cotman, Carl W.

doi:10.1016/s0306-4522(98)00134-1

Cited by 18 publications

(12 citation statements)

References 30 publications

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“…The content of NE in terminal regions in postmortem AD subjects is reduced, but the reduction does not correspond to the degree of neuronal loss (Adolfsson et al, 1979; Hoogendijk et al, 1999; Mann et al, 1981; Palmer et al, 1987; Reinikainen et al, 1988; Tomlinson et al, 1981). Similar results were observed for NE-synthesizing enzymes in the forebrain of postmortem AD subjects (Cross et al, 1981; Palmer et al, 1987; Perry et al, 1981; Russo-Neustadt et al, 1998). Recently, our laboratory showed that the remaining noradrenergic neurons in the LC of AD and a related dementing disorder, dementia with Lewy body (DLB), showed three different compensatory changes: (1) increase in the expression of tyrosine hydroxylase (TH) mRNA; (2) sprouting of dendrites into the peri-LC dendritic zone; and (3) sprouting of axonal projections into the hippocampus and prefrontal cortex (Szot et al, 2006, 2007).…”

Section: Introductionsupporting

confidence: 85%

Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

et al. 2011

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In Parkinson's disease (PD), there is a significant loss of noradrenergic neurons in the locus coeruleus (LC) in addition to the loss of dopaminergic neurons in the substantia nigra (SN). The goal of this study was to determine if the surviving LC noradrenergic neurons in PD demonstrate compensatory changes in response to the neuronal loss, as observed in Alzheimer's disease (AD). Tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) mRNA expression in postmortem LC tissue of control and age-matched PD subjects demonstrated a significant reduction in the number of noradrenergic neurons in the LC of PD subjects. TH mRNA expression/neuron did not differ between control and PD subjects, but DBH mRNA expression/neuron was significantly elevated in PD subjects compared to control. This increase in DBH mRNA expression in PD subjects is not a response to neuronal loss because the amount of DBH mRNA expression/neuron in AD subjects was not significantly different from control. Norepinephrine transporter (NET) binding site concentration in the LC of PD subjects was significantly reduced over the cell body region as well as the peri-LC dendritic zone. In PD subjects, the loss of dendrites from surviving noradrenergic neurons was also apparent with TH-immunoreactivity (IR). This loss of LC dendritic innervation in PD subjects as measured by TH-IR was not due to LC neuronal loss because TH-IR in AD subjects was robust, despite a similar loss of LC neurons. These data suggest that there is a differential response of the noradrenergic nervous system in PD compared to AD in response to the loss of LC neurons.

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Section: Introductionsupporting

confidence: 85%

Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

et al. 2011

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“…A similar result was observed when the synthesizing enzymes for NE were measured in forebrain regions Perry et al, 1981;Palmer et al, 1987;Russo-Neustadt et al, 1998). Recently, our laboratory demonstrated a significant increase in the mRNA expression for the rate limiting enzyme tyrosine hydroxylase (TH) in the LC of AD subjects (Szot et al, 2000), suggesting that the remaining neurons in the LC are compensating for the loss of noradrenergic neurons of AD subjects.…”

Section: Introductionsupporting

confidence: 80%

Compensatory Changes in the Noradrenergic Nervous System in the Locus Ceruleus and Hippocampus of Postmortem Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Szot¹,

White²,

Greenup³

et al. 2006

J. Neurosci.

215

240

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In Alzheimer's disease (AD), there is a significant loss of locus ceruleus (LC) noradrenergic neurons. However, functional and anatomical evidence indicates that the remaining noradrenergic neurons may be compensating for the loss. Because the noradrenergic system plays an important role in learning and memory, it is important to determine whether compensation occurs in noradrenergic neurons in the LC and hippocampus of subjects with AD or a related dementing disorder, dementia with Lewy bodies (DLB). We observed profound neuronal loss in the LC in AD and DLB subjects with three major changes in the noradrenergic system consistent with compensation: (1) an increase in tyrosine hydroxylase (TH) mRNA expression in the remaining neurons; (2) sprouting of dendrites into peri-LC dendritic zone, as determined by ␣ 2 -adrenoreceptors (ARs) and norepinephrine transporter binding sites; and (3) sprouting of axonal projections to the hippocampus as determined by ␣ 2 -ARs. In AD and DLB subjects, the postsynaptic ␣ 1 -ARs were normal to elevated. Expression of ␣ 1A -and ␣ 2A -AR mRNA in the hippocampus of AD and DLB subjects were not altered, but expression of ␣ 1D -and ␣ 2C -AR mRNA was significantly reduced in the hippocampus of AD and DLB subjects. Therefore, in AD and DLB subjects, there is compensation occurring in the remaining noradrenergic neurons, but there does appear to be a loss of specific AR in the hippocampus. Because changes in these noradrenergic markers in AD versus DLB subjects were similar (except neuronal loss and the increase in TH mRNA were somewhat greater in DLB subjects), the presence of Lewy bodies in addition to plaques and tangles in DLB subjects does not appear to further affect the noradrenergic compensatory changes.

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“…Sprouting of the surviving noradrenergic neurons in the LC of subjects with dementia has been suggested by a variety of other studies (Adolfsson et al, 1979;Cross et al, 1981;Mann et al, 1981;Perry et al, 1981;Tomlinson et al, 1981;Gottfries et al, 1983;Raskind et al, 1984;Palmer et al, 1987;Reinikainen et al, 1988;Tohgi et al, 1992;Elrod et al, 1997;Russo-Neustadt et al, 1998;Hoogendijk et al, 1999;Szot et al, 2000). The sprouting observed in postmortem dementia subjects is consistent with the sprouting of noradrenergic neurons in rodents after DSP-4 induced neuronal loss (Fritschy et al, 1990;Fritschy and Grzanna, 1992 …”

Section: Resultssupporting

confidence: 54%

“…There is a significant loss of noradrenergic neurons in the LC in AD (Mann et al, 1980;Tomlinson et al, 1981;Bondareff et al, 1982;Marcyniuk et al, 1986;Chan-Palay and Asan, 1989;German et al, 1992). However, the surviving neurons in the LC appear to be compensating for the neuronal loss (Adolfsson et al, 1979;Cross et al, 1981;Mann et al, 1981;Perry et al, 1981;Tomlinson et al, 1981;Gottfries et al, 1983;Raskind et al, 1984;Palmer et al, 1987;Reinikainen et al, 1988;Tohgi et al, 1992;Elrod et al, 1997;Russo-Neustadt et al, 1998;Hoogendijk et al, 1999;Szot et al, 2000). Recently, our laboratory showed that the remaining noradrenergic neurons in the LC of AD and a related dementing disorder, dementia with Lewy bodies (DLB), showed three different compensatory changes: (1) an increase in tyrosine hydroxylase mRNA expression in the remaining neurons; (2) sprouting of dendrites into the peri-LC dendritic zone, as determined by α 2 -adrenoreceptor (AR) and norepinephrine transporter binding sites; and (3) sprouting of axonal projections into the hippocampus as determined by α 2 -ARs (Szot et al, 2006).…”

mentioning

confidence: 99%

Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia: Evidence of compensatory changes

et al. 2007

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In Alzheimer's disease (AD) there is a significant loss of locus coeruleus (LC) noradrenergic neurons. However, recent work has shown the surviving noradrenergic neurons to display many compensatory changes, including axonal sprouting to the hippocampus. The prefrontal cortex (PFC) is a forebrain region that is affected in dementia, and receives innervation from the LC noradrenergic neurons. Reduced PFC function can reduce cognition and disrupt behavior. Because the PFC is an important area in AD, we determined if noradrenergic innervation from the LC noradrenergic neurons is maintained and if adrenoreceptors are altered postsynaptically. Presynaptic PFC α 2 -adrenoreceptor (AR) binding site density, as determined by 3 H-RX821002, suggests that axons from surviving noradrenergic neurons in the LC are sprouting to the PFC of subjects with dementia. Changes in postsynaptic α 1 -AR in the PFC of subjects with dementia indicate normal to elevated levels of binding sites. Expression of α 1 -AR subtypes (α 1A -and α 1D -AR) and α 2C -AR subtype mRNA in the PFC of subjects with dementia is similar to what was observed in the hippocampus with one exception, the expression of α 1A -AR mRNA. The expression of the α 1A -AR mRNA subtype is significantly reduced in specific layers of the PFC in subjects with dementia. The loss of α 1A -, α 1D -and α 2C -AR mRNA subtype expression in the PFC may be attributed to neuronal loss observed in dementia. These changes in postsynaptic AR would suggest a reduced function of the PFC. Consequence of this reduced function of the PFC in dementia is still unknown but it may affect memory and behavior.

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Preserved cerebellar tyrosine hydroxylase-immunoreactive neuronal fibers in a behaviorally aggressive subgroup of Alzheimer's disease patients

Cited by 18 publications

References 30 publications

Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

Compensatory Changes in the Noradrenergic Nervous System in the Locus Ceruleus and Hippocampus of Postmortem Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia: Evidence of compensatory changes

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