Differential sensitivity of calbindin and PARV immunoreactive cells in the striatum to excitotoxins
Department of Anatomy, School of Medicine, University of Auckland, New Zealand. Brain Research
(Impact Factor: 2.84).
05/1991; 546(2):329-35. DOI: 10.1016/0006-8993(91)91497-O
The neurotoxic effects of ibotenic acid, quinolinic acid and kainic acid on cells in the rat striatum were investigated using immunocytochemistry with antibodies to the calcium binding proteins, calbindin and parvalbumin. The results showed that both ibotenic acid and quinolinic acid affected calbindin and parvalbumin cells to the same extent. However, parvalbumin immunopositive neurons were more sensitive than calbindin immunopositive neurons to the neurotoxic effects of kainic acid. Although the reason for this increased sensitivity of parvalbumin striatal neurons to kainic acid is unclear, these results suggest that the neurotoxicity produced by kainic acid is different to that occurring with quinolinic acid and ibotenic acid.
Available from: Stuart Maudsley
- "Syntaxins are a group of synaptic plasma membrane proteins that were first demonstrated to physically interact with PS-1 by Smith et al.  and were subsequently shown, in vitro, to alter APP processing via this interaction with PS-1, resulting in an attenuation of secreted Aβ . It is also interesting to note that in the hippocampus there is a specific up-regulation of ubiquitin, perhaps in an attempt to attenuate the deleterious effects of Aβ and hyperphosphorylated tau upon the ubiquitin-proteasome system (UPS: ). Taken together, these three proteins and their relative regulation in the hippocampus, relative to the cortex, suggests that perhaps the hippocampus is being preferentially protected, potentially at the expense of cortical tissue. "
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ABSTRACT: Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid beta-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders.
PLoS ONE 07/2008; 3(7):e2750. DOI:10.1371/journal.pone.0002750 · 3.23 Impact Factor
Available from: Heinz Grunze
- "PV(ϩ) interneurons are thought to exert an inhibitory control over excitatory pyramidal cells through recurrent inhibition; CR(ϩ) interneurons , on the other hand, mainly establish synapses with other interneurons thereby supporting the synchronization of local neuronal networks (Gulyas et al 1996). It is interesting to note that PV(ϩ) interneurons seem to be more vulnerable towards excitotoxicity than other subpopulations, especially than the CR(ϩ) subtype (Lukas and Jones 1994; Waldvogel et al 1991). "
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ABSTRACT: The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) in healthy humans and their ability to exacerbate psychotic symptoms in schizophrenic patients have promoted a view of schizophrenia as being related to altered glutamatergic neurotransmission.
This prompted us and others to develop animal models for psychosis based on a glutamatergic approach. Pharmacological induction of a state of impaired glutamatergic neurotransmission based on chronic, low-dose application of MK-801, a highly selective noncompetitive NMDA antagonist, revealed marked parallels between schizophrenia and our animal model.
MK-801 altered the expression of NR1 splice variants and NR2 subunits of the NMDA receptor in a pattern partially resembling the alterations detected in schizophrenia. Ultrastructurally, the number of gamma-aminobutyric-acid (GABA)ergic parvalbumin-positive interneurons was relatively decreased, a finding which again parallels observations in post mortem brain from schizophrenic patients. As a functional consequence, local inhibition of pyramidal cells which is largely mediated by recurrent axon collaterals, originating from GABAergic interneurons, was altered. Not unexpectedly, these animals showed cognitive deficits resembling findings in schizophrenic humans.
These convergent lines of evidence suggest that our approach has a significant potential of serving as a model of the pathobiology of several aspects of psychosis and consequently could contribute to the development of new therapeutic strategies.
Biological Psychiatry 05/2006; 59(8):721-9. DOI:10.1016/j.biopsych.2005.08.029 · 10.26 Impact Factor
Available from: John G McHaffie
- "Although the physiological significance of these calcium-binding proteins in the SC is unclear, based on findings in other brain regions, their function has been linked to the modulation of neuronal firing patterns (Chard et al. 1993; Du et al. 1996; Kawaguchi and Kubota 1993; Li et al. 1995). In addition, their calcium buffering capacity may play an especially critical role in protection from N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity (Waldvogel et al. 1991) that can accompany high levels of evoked activity. "
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ABSTRACT: The distribution of the calcium-binding proteins calbindin D-28K and parvalbumin was examined in newborn and adult superior colliculus of cat and rhesus monkey using immunohistochemical techniques. In adult animals of both species, calbindin-immunoreactive neurons had a three-tiered arrangement: one band was present in the upper aspects of the superficial laminae, a second in the intermediate laminae, and a third in the deep laminae. The intermediate tier was less obvious in the monkey, whereas the deep tier was less pronounced in the cat. Parvalbumin-immunoreactive neurons had a complementary distribution to calbindin-immunoreactive neurons within these laminae in both species, although the segregation of calbindin immunoreactivity and parvalbumin immunoreactivity in the superficial laminae was not as precise in the monkey as it was in the cat. At birth, calbindin immunoreactivity in the newborns of both species was remarkably mature, with its three-tiered distribution clearly evident. By contrast, parvalbumin immunoreactivity was distinctly different in the newborn cat than in the newborn monkey: whereas parvalbumin immunoreactivity in the newborn monkey was already very similar to its adult-like pattern, the pattern in the newborn cat was quite immature. The superficial laminae of the newborn cat were virtually devoid of parvalbumin immunoreactivity, and, although the intermediate laminae displayed robust parvalbumin-immunoreactive neuropil, comparatively fewer parvalbumin-immunoreactive neurons were observed. Conspicuously few in number were the large multipolar neurons in the intermediate laminae, which give rise to the descending efferents to the brainstem. However, parvalbumin-immunoreactive neurons were present within the deep laminae, suggesting a ventral-to-dorsal maturational gradient in parvalbumin expression that parallels the ventral-to-dorsal gradient of neurogenesis. The differences in parvalbumin immunoreactivity observed between these two species at parturition are consistent with the advanced visual and visuomotor capabilities of the newborn monkey and the absence of visually related behaviors in the newborn cat.
Experimental Brain Research 01/2002; 141(4):460-70. DOI:10.1007/s00221-001-0908-5 · 2.04 Impact Factor
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