Biomedical subjects

Seyed Khosrow Tayebati

Publications and source records attributed to Seyed Khosrow Tayebati.

11 recordsLinked to original sources

PubMed2005

Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission.

The effects of association of cholinergic precursors choline or choline alphoscerate with the cholinesterase inhibitor rivastigmine on acetylcholine levels and [(3)H]hemicholinium-3 binding were assessed in rat frontal cortex, hippocampus and striatum. Acetylcholine immunoreactivity was also evaluated in cerebrocortical cholinergic fibers by immunohistochemistry. Choline alphoscerate or rivastigmine, but not choline increased acetylcholine levels as well as [(3)H]hemicholinium-3 binding used as a marker of high affinity cholinergic transporter. The association of choline alphoscerate with rivastigmine dose-dependently increased both acetylcholine levels and [(3)H]hemicholinium-3 binding. Rivastigmine alone or in association with either choline or choline alphoscerate decreased acetylcholinesterase (AChE), whereas choline or choline alphoscerate alone did not affect AChE activity. Choline alphoscerate or rivastigmine alone or in association, but not choline increased acetylcholine immunoreactivity in nerve fibers supplying cerebral cortex. These data suggest that combination of a suitable precursor of brain acetylcholine such as choline alphoscerate and of a cholinesterase inhibitor may represent an association worthwhile of being further investigated as a cholinergic replacement therapy in pathologies characterized by altered cholinergic neurotransmission.

Acetylcholine↗

PubMed2005

Muscarinic cholinergic receptor subtypes in cerebral cortex of Fisher 344 rats: a light microscope autoradiography study of age-related changes.

The density and localization of muscarinic cholinergic M1-M5 receptor subtypes was investigated in frontal and occipital cortex of male Fisher 344 rats aged 6 months (young-adult), 15 months (mature) and 22 months (senescent) by combined kinetic and equilibrium binding and light microscope autoradiography. In 6-month-old rats, the rank order density of muscarinic cholinergic receptor subtypes was M1>M2>M4>M3>M5 both in frontal and occipital cortex. A not homogeneous distribution of different receptor subtypes throughout cerebrocortical layers of frontal or occipital cortex was found. In frontal cortex silver grains corresponding to the M1 and M2 receptor subtypes were decreased in 15- and 22-month-old groups. The M3 receptor density was remarkably and moderately decreased in layers II/III and V, respectively, of rats aged 15 and 22 months. A reduced M4 receptor density was observed in layer I and to a lesser extent in layer V of mature and senescent rats, whereas no age-related changes of M5 receptor were found. In occipital cortex a diminution of M1 receptor was observed in layers II/III and V of mature and senescent rats. The M2 receptor expression decreased in layer I of 15- and 22-month-old senescent rats, whereas M3-M5 receptors were unchanged with exception of a slight decrease of the M4 receptor in layer IV and of M5 receptor in layers II/III. These findings indicate a different sensitivity to aging of muscarinic receptor subtypes located in various cerebrocortical layers. This may account for the difficulty in obtaining relevant results in manipulating cholinoceptors to counter age-related impairment of cholinergic system.

Aging↗

PubMed2005

Animal models of cognitive dysfunction.

The increased life expectancy in industrialised countries in the last half century has also brought to a greater incidence of neurological disorders, including neurodegenerative diseases and developing in a rather long time. In this respect, Alzheimer's disease (AD), for the large incidence, and the dramatic loss of autonomy caused by its cognitive and behavioural symptoms represents one of the main challenges of modern medicine. Although AD is a typical human disease and probably includes several nosographic entities, the use of animal models may contribute to understand specific aspects of pathophysiology of the disease. The most widely used animal models are rodents and non-human primates. In this review different animal models characterised by impaired cognitive functions are analysed. None of the models available mimics exactly cognitive, behavioural, biochemical and histopathological abnormalities observed in neurological disorders characterised by cognitive impairment. However, partial reproduction of neuropathology and/or cognitive deficits of Alzheimer's disease (AD), vascular dementia and dementia occurring in Huntington's and Parkinson's diseases, or in other neurodegenerative disorders may represent a basis for understanding pathophysiological traits of these diseases and for contributing to their treatments.

Animals↗

PubMed2004

Identification of adenosine A1 and A3 receptor subtypes in rat pial and intracerebral arteries.

The expression and microanatomical localization of adenosine A1 and A3 receptor subtypes were investigated in rat pial and intracerebral arteries by immunoblotting, immunohistochemistry and in situ hybridization techniques. Pial artery membranes develop immune bands of approximately 79 and 52 kDa when exposed to anti-A1 and anti-A3 receptor protein antibodies respectively. Sympathectomy performed by bilateral superior cervical ganglionectomy did not change the pattern of adenosine A1 or A3 receptor immunochemistry. Sections of pial and intracerebral arteries processed for A1 or A3 receptor protein immunohistochemistry developed immune reaction in the tunica media, within arterial smooth muscle. A1 receptor immunoreactivity was more pronounced in large-sized compared to medium- and small-sized pial arteries and was stronger in small than in medium- or large-sized intracerebral arteries. A3 receptor immunoreactivity was more pronounced in smaller sized pial arteries compared to larger pial arteries, whereas no differences in the intensity of immune staining were noticeable between different sized intracerebral arteries. In situ hybridization histochemistry revealed a strong signal for A1 receptor and a moderate signal for A3 receptor in the tunica media of pial arteries, within smooth muscle. The present study indicates that rat pial and intracerebral arteries besides to the well characterized A2a and A2b receptors, express also A1 and A3 receptor subtypes. The identification of cerebrovascular A1 and A3 adenosine receptor subtypes may stimulate further research for detailing the mechanism(s) of regulation of cerebral circulation by adenosine.

Animals↗

PubMed2004

Age-related changes of muscarinic cholinergic receptor subtypes in the striatum of Fisher 344 rats.

Striatum expresses a cholinergic system involved in the regulation of its activity and changes in striatal cholinergic receptors may be related to cognitive impairment. This study has investigated muscarinic cholinergic M1-M5 receptor subtype expression in striatum of Fischer 344 rats aged 6 (young), 15 (adult) and 22 months (senescent) to assess the contribution of different muscarinic cholinergic receptor subtypes in age-related changes of striatal cholinergic neurotransmission. Western blot analysis revealed the expression of the M1-M5 muscarinic receptor subtytpes in the striatum of rats of the three age groups investigated. Both radioligand binding assay and light microscope autoradiography showed in young rats a M4>M1>M2>M3>M5 rank order of receptor density. With the exception of M1 receptor, the density of which is similar in the dorsal (motor) and ventral (limbic) striatum, other receptor subtypes were more abundant in ventral than in dorsal striatum. M1 receptor expression was unchanged between young and adult rats and decreased in senescent animals both in dorsal and ventral striatum. In dorsal striatum M2 and M5 receptor expression did not show age-related changes, whereas in ventral striatum it was slightly decreased in adult rats compared to young or senescent cohorts. M3 receptor expression did not show age-related modifications, whereas a progressive age-related decrease of M4 receptor was found, both in dorsal and ventral striatum. These data indicate a heterogeneous response to age of different muscarinic receptor subtypes. Striatal cholinergic markers are thought to correlate with cognitive impairment in aged rats. In view of this, the identification of age-related changes of striatal muscarinic receptor subtypes may contribute to develop cholinergic strategies to counter cholinergic neurotransmission changes occurring with aging.

Aging↗

PubMed2004

Glial fibrillary acidic protein and vimentin expression is regulated by glucocorticoids and neurotrophic factors in primary rat astroglial cultures.

The neurotrophic factors epidermal growth factor (EGF), basic fibroblast growth factor, (bFGF), insulin-like growth factor I (IGF-I) and insulin (INS) regulate neural and astroglial cell functions. Glucocorticoids may influence the metabolism of astroglial compartment and are key hormones in neurodegenerative events. This study was designed to assess the interactions between growth factors and dexamethasone (DEX) on cytoskeletal proteins (GFAP and vimentin) expression in 25 days in vitro (DIV) astrocyte cultures. An increase in GFAP and vimentin expression was observed after 12 h pretreatment with bFGF and subsequent treatment for 60 h with DEX. GFAP immunoreactivity was decreased after 24 h progression growth factors (EGF, IGF-I and INS) addition, when compared to control 36 h DEX and bFGF-pretreated cultures for the last 12 h. Vimentin immunoreactivity was decreased after 12 h bFGF pretreatment and subsequent 60 h DEX addition in astrocyte cultures compared to 12 h bFGF-pretreated ones. Pretreatment for 36 h with DEX plus bFGF in the last 12 h and subsequent treatment for 24 h with DMEM (Dulbecco's modified Eagle medium; DMEM) + BSA (bovine serum albumine) (harvesting), or with progression growth factors (EGF, IGF-I or INS) alone or two of them together, stimulated GFAP expression, compared to untreated controls. Immunochemical analysis of the mitogen-activated protein kinase ERK2 suggests an involvement of this enzyme in the control of GFAP expression. The above findings support the view of an interactive and complex dialogue between growth factors and glucocorticoids during astroglial cell proliferation and maturation in culture. This may have implications in therapeutic approach of neurologic disorders associated with astrogliosis, including cerebrovascular disease.

Animals↗

PubMed2004

Effect of treatment with the cholinesterase inhibitor rivastigmine on vesicular acetylcholine transporter and choline acetyltransferase in rat brain.

A decline of cholinergic neurotransmission probably contributes to cognitive dysfunction occurring in Alzheimer's disease (AD) and vascular dementia (VaD). Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors are the only drugs authorized for symptomatic treatment of AD and are also under investigation for VaD. The present study has investigated the influence of two doses of the AChE inhibitor rivastigmine (0.625 mg/Kg/day and 2.5 mg/Kg/day) on vesicular acetylcholine transporter (VAChT) and on choline acetyltransferase (ChAT) expression in frontal cortex, hippocampus, striatum and cerebellum of normotensive and spontaneously hypertensive rats (SHR). Cholinergic markers were assessed by immunochemical (Western blotting) and immunohistochemical techniques. In frontal cortex and striatum of normotensive rats, treatment with the lower dose (0.625 mg/Kg/day) of rivastigmine had no effect on VAChT immunoreactivity and increased slightly ChAT protein immunoreactivity. The higher dose (2.5 mg/Kg/day) of the compound increased significantly VAChT and ChAT protein immunoreactivity. In hippocampus rivastigmine induced a concentration-dependent increase of VAChT protein expression and no significant changes of ChAT protein expression. A similar pattern of VAChT and ChAT protein expression was observed in control SHR, whereas treatment of SHR with rivastigmine induced a more pronounced increase of VAChT protein immunoreactivity in frontal cortex, hippocampus and striatum compared to normotensive rats. Our data showing an increase of VAChT after treatment with rivastgmine further support the notion of an enhancement of cholinergic neurotransmission by AChE/ChE inhibitors. The observation of a greater expression of this cholinergic marker in SHR suggest that AChE inhibition may provide beneficial effects on cholinergic neurotransmission in an animal model of VaD.

Animals↗

PubMed2002

Cholinergic innervation of pial arteries in senescent rats: an immunohistochemical study.

Perivascular acetylcholine (ACh)-immunoreactive nerve fibres were demonstrated in basilar and middle cerebral arteries, in pial arteries and arterioles and in intracerebral arteries of male Fisher 344 rats of 6 months (young), 15 months (adult) and 22 months (senescent). Analysis included whole mounts of basilar and middle cerebral arteries, of pial arteries and sections of brain including pia-arachnoid membrane to demonstrate the localization of nerve fibres throughout the wall of pial and of intracerebral arteries. ACh-immunoreactive nerve fibres were demonstrated by indirect immunohistochemistry using a polyclonal anti-ACh antibody and their relative density was quantified. Perivascular ACh-immunoreactive nerve fibres were located in basilar and middle cerebral arteries, in pial arteries and arterioles and in intracerebral arteries. These fibres were found in the adventitia and adventitia-media border with a higher density in pial rather than in intracerebral arteries. A decrease of ACh-immunoreactive nerve fibres was observed both in pial and intracerebral arteries of adult or senescent rats compared to younger cohorts. The direct demonstration of ACh-immunoreactive nerve fibres in the cerebrovascular tree may contribute to evaluate the influence of experimental and pathological conditions on cerebrovascular cholinergic neuroeffector mechanisms, including a role of cholinergic innervation in the pathophysiology of cerebrovascular disease of the elderly.

Acetylcholine↗

PubMed2002

Muscarinic cholinergic receptor subtypes in the hippocampus of aged rats.

In spite of the suggestion of impaired muscarinic function in adult-onset cognitive disorders, data on the expression of muscarinic receptors in the hippocampus as a function of age are inconsistent. One reason may be that the majority of investigations were unable to differentiate the five brain muscarinic receptors subtypes. In this study, using a protocol based on a combination of both kinetic and equilibrium binding approaches, we have assessed the expression and the density of M1-M5 muscarinic cholinergic receptors in the hippocampus of Fisher 344 rats aged 6, 15 and 22 months. An age-related decrease of the density of M1 receptor was found in pyramidal neurons of the CA1 subfield. In this area, other subtypes of muscarinic receptors were unchanged with the exception of a loss of M2 receptor in the radial layer. In the CA3 subfield, receptor changes involved M2, M3 and M5 subtypes, whereas in the dentate gyrus, the main changes affected M1 and M2 receptors of the granular layer and M2 and M3 receptors of the molecular layer. The above findings indicate that analysis of age-related changes of different muscarinic cholinergic receptors might represent a useful contribution to identifying the basis of cholinergic neurotransmission impairment in adult-onset cognitive dysfunction.

Aging↗

PubMed2002

Expression of peripheral blood lymphocyte muscarinic cholinergic receptor subtypes in airway hyperresponsiveness.

The expression of muscarinic cholinergic receptor subtypes was investigated in peripheral blood lymphocytes (PBL) of bronchial asthma patients by a combined kinetic and equilibrium labeling technique for radioligand binding assay of muscarinic cholinergic receptor subtypes and by receptor immunochemistry and immunocytochemistry. An increased expression of M2 and to a lesser extent of M5 receptors and no changes of M4 receptor were observed in PBL of asthmatics compared to control individuals. The increase was related to bronchial hyperresponsiveness detected by methacholine challenge test. Analysis of M3 receptor expression revealed biphasic changes, with a decreased receptor density in patients with normal, mild and moderate responses to methacholine test and a recovery to levels similar to those found in healthy individuals in severe responders to methacholine test. The demonstration of a different expression of lymphocyte muscarinic receptors in asthma suggests that cholinergic system may participate to a molecular framework influencing immune functions in asthma.

Acetylcholine↗

PubMedDate not supplied

Stroke prevention and statin treatment.

Randomized trials with statins have shown a modest but significant absolute reduction in the incidence of stroke in patients with a previous myocardial infarction. The reasons for the positive statin effect on stroke endpoint are unclear, because a link between serum cholesterol level and stroke never has been established. However, positive results of statin trials were mainly obtained in patients with an average or a low serum cholesterol level. Statins have a good overall safety profile. Statins reduced stroke incidence in high-risk (mainly coronary heart disease, diabetics, and hypertensives) population even with a normal baseline blood cholesterol level. In patients with prior strokes, statins reduce the incidence of coronary events, but it is not yet proven if drugs of this class actually reduce the incidence of recurrent strokes in terms of secondary prevention.

Clinical Trials as Topic↗