Biomedical subjects

E G Stopa

Publications and source records attributed to E G Stopa.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Circadian locomotor activity and core-body temperature rhythms in Alzheimer's disease.

Sleep-wake cycle disturbances suggest that circadian rhythms may be disrupted in patients with Alzheimer's disease (AD). In this study, we examined the circadian rhythms of core-body temperature and locomotor activity in 28 patients with probable AD and 10 healthy controls. AD patients had higher percent nocturnal activity than controls, corresponding to the clinical picture of fragmented sleep. The amplitude of the activity cycle in the AD patients was lower than that of controls and the acrophase of this cycle in AD patients was 4.5 h later. There was no difference in the amplitude of the core-body temperature circadian rhythm, but AD patients had delayed temperature acrophases. A subgroup of AD patients with large mean time differences between the acrophases of their activity and temperature cycles had lower temperature amplitudes and greater activity during the night. These findings suggest that a subgroup of AD patients with impaired endogenous pacemaker function may have a diminished capacity to synchronize the rhythm of core-body temperature with the circadian cycle of rest-activity. This circadian rhythm dysfunction may partly explain the fragmented nocturnal sleep exhibited by these patients.

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PubMedDate not supplied

Agrin and microvascular damage in Alzheimer's disease.

Heparan sulfate proteoglycans (HSPGs) are ubiquitously present within the perivascular basement membrane, and have been shown to be altered in patients with Alzheimer's Disease (AD). Although the HSPG agrin clearly orchestrates the differentiation of the neuromuscular junction, its role in the brain remains unclear. Growing evidence suggests that agrin may be an important vascular basement membrane (VBM)-associated HSPG. In previous studies, we demonstrated that agrin is present throughout the brain microvasculature, as well as in neuronal cell bodies. AD brains exhibited fragmentation of VBM-associated agrin. Agrin immunoreactivity was also seen within senile plaques and neurofibrillary tangles. These changes were accompanied by the appearance of an additional pool of insoluble agrin. In the present study, we provide further evidence for microvascular damage in AD, by examining the distribution of agrin and laminin within the VBM, and by measuring the agrin concentration within hippocampus and prefrontal cortex. Furthermore, we assessed blood-brain-barrier (BBB) leakage by examining the perivascular distribution of prothrombin immunoreactivity. Soluble agrin levels were increased approximately 30% in Braak stage III-VI AD patients relative to age-matched controls. Furthermore, agrin and laminin exhibited identical patterns of VBM fragmentation in AD and colocalized with beta-amyloid in senile plaques. Microvascular changes were associated with the appearance of perivascular prothrombin immunoreactivity. Our data suggest that agrin is an important VBM-associated HSPG in the brain and that agrin levels are altered in association with microvascular damage in AD.

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PubMedDate not supplied

Somatostatin-gene expression in the postmortem adult and fetal human brain.

We have examined the utility of in situ hybridization for detecting pre-prosomatostatin mRNA in postmortem human brain. In preliminary studies, Northern blot analysis using a rat model, which simulates the normal pattern of human post-mortem brain cooling, revealed retention of significant amounts of hybridizable somatostatin mRNA relative to control levels between 12 and 24 hours after death. mRNA extracted from postmortem fetal human brain specimens showed hybridization to cRNA probes directed against pre-prosomatostatin mRNA. We thus undertook in situ hybridization studies. Antisense RNA probes were hybridized to neurons that expressed pre-prosomatostatin in 10-microns sections of adult and fetal human brain. The distribution of pre-prosomatostatin mRNA-containing neurons was similar to that observed for somatostatin-like immunoreactivity; however, the in situ hybridization technique was a more sensitive marker of neuronal perikarya. Our results indicate that hybridization to pre-prosomatostatin mRNA is a useful method for localizing these peptidergic neurons in postmortem human brain tissue.

Adult↗

PubMedDate not supplied

Neuropeptide Y receptor distribution and regulation in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus).

The suprachiasmatic nucleus (SCN) receives a direct photic projection from the retina, the retinohypothalamic tract (RHT), and an indirect photic projection from the intergeniculate leaflet of the thalamus, the geniculohypothalamic tract (GHT). The primary neurochemical signal in the GHT appears to be neuropeptide Y (NPY), and several lines of evidence indicate that NPY may be involved in determining the response of the SCN to light. The purpose of the present study was (i) to localize NPY binding sites in the hamster SCN and to compare the distribution of these binding sites with the terminal field of the RHT and (ii) to determine if SCN levels of NPY binding change during the day. RHT fibers, defined using the carbocyanine dye DiI, were localized primarily within the ventrolateral region of the SCN. The distribution of NPY receptors, as visualized by 125I-peptide YY (PYY) binding, overlapped the projection field of the RHT. Specific binding of 125I-PYY was significantly greater in the ventrolateral SCN than in the medial SCN. To determine whether NPY binding changes during the day, the levels of 125I-PYY in the SCN were determined 4 h before the onset of darkness, 1 h before the onset of darkness and 2 h after the onset of darkness in hamsters housed in a 14:10 light-dark cycle. The levels of binding at 4 and 1 h before dark onset were significantly lower than 2 h after the onset of darkness. In contrast, no significant differences were observed in 125I-PYY binding over these same sampling intervals in either the medial preoptic area or the lateral hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

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