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L F Agnati

Publications and source records attributed to L F Agnati.

At least 55 records · Page 3Linked to original sources
PubMed1998

Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain.

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.

Animals↗
PubMed1998

On the relationship of 5-hydroxytryptamine neurons to 5-hydroxytryptamine 2A receptor-immunoreactive neuronal processes in the brain stem of rats. A double immunolabelling analysis.

The distribution of 5-HT2A receptor immunoreactivity in the brain stem was studied by means of a commercial 5-HT2A mouse monoclonal antibody against the N-terminal portion of the receptor (amino acids 1-72). The 5-HT2A immunoreactivity demonstrated in the nerve terminal or dendritic-like structures of regions of the nucleus raphe pallidus, nucleus interfascicularis, motor nucleus of the trigeminal nerve, the ventral and dorsal tegmental nuclei and the median eminence by means of double immunofluorescence procedures were shown to be associated with 5-HT immunoreactive cell body-dendritic and/or nerve terminal structures. Besides synaptic transmission the relationships are compatible with the existence of short distance volume transmission (in the microm range) in 5-HT2A mediated 5-HT communication through terminal (5-HT)-terminal (5-HT2A) or soma/dendro (5-HT)-terminal (5-HT2A) and terminal (5-HT)-dendritic (5-HT2A) interactions in discrete brain stem nuclei.

Animals↗
PubMed1998

The emergence of the volume transmission concept.

Interneuronal communication in the central nervous system (CNS) have always been of basic importance for theories on the cerebral morphofunctional architecture. Our group has proposed that intercellular communication in the brain can be grouped into 2 broad classes based on some general features of the transmission: wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both morphological and functional evidence indicates that dopamine (DA) synapses in striatum are 'open' synapses, i.e., synapses which favor diffusion of the transmitter into the surrounding ECF and observations are compatible with the view that DA varicosities can synthesize, store and release DA for VT. The DAergic mesostriatal transmission has, therefore, been examined by several groups to give experimental support to VT. Moreover, due to its minor structural requirements, VT may become prevalent under some pathological conditions, e. g. Parkinson's disease. In animal models of DAergic pathway degeneration, it has been shown that a compensatory activation of surviving DA terminals may lead to a preferential potentiation of VT. WT and VT favor different and complementary types of computation. VT is markedly slower and less safe than WT, but has minor spatial constraints and allows the reach of a large number of targets. Models of neuronal systems integrating classical neuronal circuits and diffusible signals begin to show how WT and VT may interact in the neural tissue.

Animals↗
PubMed1998

Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine A1/dopamine D1 receptor interactions in the basal ganglia.

An analysis at the network and membrane level has provided evidence that antagonistic interactions between adenosine A2A/dopamine D2 and adenosine A1/dopamine D1 receptors in the ventral and dorsal striatum are at least in part responsible for the motor stimulant effects of adenosine receptor antagonists like caffeine and for the motor depressant actions of adenosine receptor agonists. The results obtained in stably cotransfected cells also underline the hypothesis that the intramembrane A2A/D2 and A1/D1 receptor interactions represent functionally important mechanisms that may be the major mechanism for the demonstrated antagonistic A2A/D2 and A1/D1 receptor interactions found in vivo in behavioural studies and in studies on in vivo microdialysis of the striopallidal and strioentopeduncular GABAergic pathways. A major mechanism for the direct intramembrane A2A/D2 and A1/D1 receptor interactions may involve formation of A2A/D2 and A1/D1 heterodimers leading to allosteric changes that will alter the affinity as well as the G protein coupling and thus the efficacy to control the target proteins in the membranes. This is the first molecular network to cellular integration in the nerve cell membrane and may be well suited for a number of integrated tasks and can be performed in a short-time scale, in comparison with the very long-time scale observed when receptor heteroregulation involves phosphorylation or receptor resynthesis. Multiple receptor-receptor interactions within the membranes through formation of receptor clusters may lead to the storage of information within the membranes. Such molecular circuits can represent hidden layers within the membranes that substantially increase the computational potential of neuronal networks. These molecular circuits are biased and may therefore represent part of the molecular mechanism for the storage of memory traces (engrams) in the membranes.

Animals↗
PubMed1997

Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia.

Endothelin-1 (ET-1) was unilaterally applied onto the surface of the dorsal frontoparietal cortex of the rat. Cortical blood flow measurements using laser-Doppler flowmetry demonstrated dose-dependent reductions of frontoparietal cortical blood flow. Histological analysis demonstrated dose-related lesions and the time course was followed using MRI. The lesions appear to be associated with a large penumbra area indicated by morphological characteristics. Thus, cortical surface exposure to ET-1 may produce graded lesions of the frontoparietal cortex related to local ischemia.

Animals↗
PubMed1997

Possible involvement of G-proteins in the regulation of striatal dopamine D2 receptor affinity by cholecystokinin octapeptide.

A G(i)-protein antibody AS/7 at 1:10 dilution significantly increased the K(d) values of the D2 agonist [3H]N-propylnorapomorphine (NPA) binding sites in the rat striatal membranes, and coincubation with sulphated cholecystokinin octapeptide (CCK-8; 1 nM) did not further increase the K(d) values. A GTP analogue guanylyl-imidodiphosphate (GMP-PNP) at 100 microM markedly increased the K(d) values of the [3H]NPA binding sites in the rat forebrain sections, and coincubation with CCK-8 (1 nM) again did not produce a further increase in the K(d) values. The present results indicate that abnormal activity of G-proteins abolished the ability of CCK-8 to reduce the D2 receptor affinity in the brain.

Animals↗
PubMed1997

NPY Y1 receptor like immunoreactivity exists in a subpopulation of beta-endorphin immunoreactive nerve cells in the arcuate nucleus: a double immunolabelling analysis in the rat.

Double immunolabelling immunohistochemistry in the arcuate nucleus of the rat demonstrates that neuropeptide Y (NPY) Y1 receptor like immunoreactivity is strongly present in a subpopulation of beta-endorphin immunoreactive nerve cell bodies, while the small NPY immunoreactive nerve cell bodies located medially lack NPY Y1 receptor like immunoreactivity. The NPY Y1 like immunoreactive nerve cell bodies lie in an arcuate area rich in NPY immunoreactive nerve terminals forming an uniform plexus. It is postulated that NPY Y1 receptors in beta-endorphin neurons may mediate some actions of NPY on motivational processes and pain control as well as on hypophyseal hormone secretion, involving at the least in part a regulation of the tubero-infundibular DA neurons.

Amino Acid Sequence↗
PubMed1997

Regional distribution of neural cell adhesion molecule immunoreactivity in the adult rat telencephalon and diencephalon. Partial colocalization with heparan sulfate proteoglycan immunoreactivity.

In the present paper immunocytochemical analysis at the fluorescence microscopical level has been performed of neural cell adhesion. molecule (NCAM) immunoreactivity in the adult rat tel- and diencephalon in order to further substantiate the highly selective neuronal localization of NCAM immunoreactivity, using an affinity purified rabbit antiserum recognizing homologous NCAM proteins from rat brain. Also, double immunolabelling experiments were performed with monoclonal antibodies specific for heparan sulfate related epitopes or gamma-aminobutyric acid (GABA) to establish in which cell populations a colocalization existed with immunoreactive heparan sulfate proteoglycans of GABA. Within the neocortex NCAM immunoreactivity was exclusively localized to the area of the cell membrane of soma and proximal dendrites of subsets of large pyramidal nerve cells of the layer 5 of the frontoparietal cortex. Within the dorsal hippocampus, the NCAM immunoreactivity was exclusively located to the cell surface area of the pyramidal cell bodies of area CA2. Two colour immunofluorescence procedures demonstrated a colocalization of NCAM and 3G10 but not 10E4 immunoreactivities in the cell surface area of many of the NCAM-positive nerve cell bodies of these two regions. Within the thalamus, strong NCAM immunoreactivity was exclusively demonstrated at all rostrocaudal levels of the reticular thalamic nucleus. The horizontal band of NCAM immunoreactivity was not continuous, but split up into patches of NCAM immunoreactivity within groups of nerve cell bodies. When analysing the number of cells per unitary square in the rostrocaudal direction, a significant increase of positive cells was found in the rostral and middle thirds versus the caudal third of the reticular thalamic nucleus. Many of the cell bodies with NCAM immunoreactivity in their cell surface are showed cytoplasmic GABA immunoreactivity. In the three regions shown to contain NCAM immunoreactivity, proteins of the NCAM type may play a special role for the maintenance of the synaptic structure. The findings also suggest that the sulfated proteoglycans and NCAM can interact in the regulation of cell-cell interaction via adhesion. In the reticular thalamic nucleus NCAM molecules may be part of a set of cell-adhesion molecules involved in a structural organization of the nucleus, which allows it to play a key role in relating cortical maps to thalamic maps.

Animals↗
PubMed1997

Increased potency of neuropeptide Y to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat.

The regulation by neuropeptide Y of alpha2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the alpha2A-adrenoceptor messenger RNA levels and the B(max) value of the alpha2-adrenoceptor agonist [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K(d) value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate alpha2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of alpha2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the alpha2A-adrenoceptor messenger RNA levels and the alpha2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Protective effects of delapril, indapamide and their combination chronically administered to stroke-prone spontaneously hypertensive rats fed a high-sodium diet.

1. Stroke-prone spontaneously hypertensive rats (SHRsp) have been used widely to test agents putatively capable of vascular protection. These animals present an accelerated time course of hypertension and a reduced life-span. When fed a high-sodium diet from the eighth week of life, a further acceleration in blood pressure increase is obtained, and rats start to die after 5 weeks of diet as a consequence of cerebral haemorrhage. In this model, angiotensin-converting enzyme (ACE) inhibitors were repeatedly proved to prevent vascular lesions and death. Notably, this effect was independent of any hypotensive effect. On the contrary, diuretics were shown not to be equally effective. A combination of ACE inhibitors and diuretics, although known to have synergistic effects in the therapy of hypertension, has never previously been tested. 2. Our aim was to study the effects of long-term treatment with the ACE inhibitor delapril (12 mg day-1 kg-1), the thiazide-like diuretic indapamide (1 mg day-1 kg-1), and their combination (12 and 1 mg day-1 kg-1 respectively), on the survival of SHRsp rats fed a high-sodium diet from the eighth week of life onwards. The effects of the treatments on blood pressure, body weight, food and fluid intake, diuresis, proteinuria and the appearance of lesion signs and death were assessed weekly. When control rats reached 50% mortality, they were killed, together with some drug-treated rats, to compare lesions in brain and kidney. The other drug-treated rats continued treatments until 50% mortality was reached in two treatment groups. 3. All drug treatments were able to delay death significantly when compared with control rats, which reached 50% mortality after 6 weeks of salt loading. This event was preceded by a highly significant increase in proteinuria, diuresis and fluid intake that took place 3 weeks after the increase in blood pressure over the initial range. In delapril- or indapamide-treated SHRsp these changes were never seen, even when animals started to die. In the combination-treated group, a significant increase (P < 0.01) in fluid intake and diuresis, but not proteinuria, was observed from the third week of treatment onwards. 4. Treatment with delapril or indapamide did not block the progressive increase in blood pressure as observed in control animals. However, the increase in blood pressure was markedly retarded with respect to control rats. At variance with this, in combination-treated animals blood pressure levels were maintained until the end of the experiment within the 99% confidence interval initially observed in control animals. 5. Infarctual and haemorrhagic cerebral lesions were observed in 38% of control rats; no lesions were noted in brains of age-matched rats receiving a drug treatment. Kidneys from control animals presented major degenerative lesions of glomeruli and arteries, characterized by fibrinoid necrosis. This condition was absent in drug-treated animals, which presented minor signs of ischaemic lesion. Heart hypertrophy, when heart weight was expressed as a percentage of body weight, was similar in saline-, delapril- or indapamide-treated rats. At variance with this, in combination-treated animals the heart weight to body weight ratio was significantly (P < 0.01) lower than in the other groups. 6. In conclusion, the diuretic indapamide showed similar protective effects as the ACE inhibitor delapril on acute vascular lesions and survival of SHRsp. Moreover, their combination synergized in preventing heart hypertrophy consequent to longterm hypertension. This results is probably related to the enhanced diuresis and the better control of blood pressure levels selectively found in combination-treated animals.

Analysis of Variance↗
PubMed1997

Short- and long-term changes in striatal neurons and astroglia after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: The striatum is one of the regions most sensitive to transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal degeneration are clearly detectable a few hours after the insult and attain their maximal extension 24 hours after the insult. However, for most cellular and neurochemical parameters it is not known whether some recovery occurs at later times. We examined certain cell populations in the caudate putamen at different times after transient ischemia. METHODS: Adult male Sprague-Dawley rats were subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six experimental groups were considered: control animals and ischemic animals killed 4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal cell populations were examined by means of immunocytochemistry coupled to computer-assisted image analysis: vulnerable medium spiny neurons, resistant aspiny neurons, and reactive astrocytes, labeled for their content of dopamine- and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide Y, and glial fibrillary acidic protein, respectively. RESULTS: (1) The area containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of control caudate putamen area) at 1 day after reperfusion and partially recovered at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8 months after reperfusion). (2) The appearance of reactive astrocytes was precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to 40 days after ischemia) in the lateral caudate putamen, where no DARPP-32 recovery was detected. (3) Neuropeptide Y/somatostatin-containing neurons resisted the ischemic insult and could be detected in areas devoid of DARPP-32 immunoreactive neurons as long as 8 months after reperfusion. CONCLUSIONS: The present results show a marked recovery of DARPP-32-positive neurons within 40 days after 30-minute forebrain ischemia in the medial, but not the lateral, caudate putamen. Medial caudate putamen also contains a high density of reactive astrocytes on the first day after ischemia, suggesting that astrocytic support has an important role in the spontaneous recovery of ischemic neurons.

Animals↗
PubMed1996

Evidence for receptors for hyaluronan in discrete nerve cell populations of the brain.

Evidence is presented, based on immunoblotting, immunohistochemistry and double immunolabelling procedures, for the existence of hyaluronan receptor immunoreactivity in discrete nerve cell populations of the rat brain, present within the zona compacta and the zona reticulata of the substantia nigra, the ventral tegmental area the locus coeruleus, the mesencephalic trigeminal nucleus, the nucleus of the trapezoid body, the motor trigeminal nucleus and the lateral cerebellar nucleus. With preimmune serum control, this hyaluronan receptor immunoreactivity could not be demonstrated. Double immunofluorescence immunocytochemistry, using a well-characterized hyaluronan receptor antiserum, together with the tyrosine hydroxylase antiserum, in the presence or absence of detergent, demonstrated the existence of hyaluronan receptor immunoreactivity in dopamine nerve cells of the substantia nigra and the ventral tegmental area and in noradrenaline nerve cells of the locus coeruleus, previously shown not to stain for hyaluronan. In all the nerve cells, the immunoreactivity had the appearance of punctate bodies mainly located in the cytoplasm of the perikarya of the above nerve cell populations as also shown by confocal laser microscopy in the mesencephalic trigeminal nucleus. Based on these observations, it is concluded that hyaluronan receptors exist in discrete nerve cell populations of the brain, including many noradrenaline and dopamine neurones. In all nerve cells, it is located intracellularly in bodies possibly representing clustered hyaluronan receptors undergoing endocytosis. The results open up the possibility that hyaluronan receptors may reduce high concentrations of hyaluronic acid in the surrounding matrix, thereby facilitating communication between adjacent neurones. Intracytoplasmatic hyaluronic acid may also be of special importance for neuronal plasticity, in view of the ability of hyaluronic acid to activate protein kinase activity and/or by influencing the architecture of the cytoskeleton.

Animals↗
PubMed1996

Subacute toluene exposure increases DA dysfunction in the 6-OH dopamine lesioned nigrostriatal dopaminergic system of the rat.

The potential neurotoxicity of the solvent toluene to the nigrostriatal dopaminergic system was assessed in a rat model of Parkinson's disease. Rats, 1 day after a unilateral injection of 6-hydroxydopamine (6-OH DA) into the substantia nigra, inhaled air or different concentrations of toluene (80, 300 or 1000 ppm), 6 h/day for 3 days. The animals were sacrificed 2 days after the last exposure and biochemical measurements of catecholamines and 3,4-dihydroxyphenylacetic acid (DOPAC) were performed in the neostriatum and substantia nigra. Toluene at 80 and 1000 ppm significantly enhanced the depletion of striatal DOPAC levels induced by the lesion and produced at 80 and 300 ppm a trend for intensifying the 6-OH DA-induced depletion of striatal DA stores. The alterations induced after the combined challenge to the dopaminergic nigrostriatal system may reflect endangering actions of toluene.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Regional and cellular distribution of spermidine/spermine N1-acetyltransferase (SSAT) mRNA in the rat central nervous system.

Spermidine/spermine N1-acetyltransferase (SSAT) is the key enzyme responsible for polyamine interconversion. SSAT mRNA (visualized by in situ hybridization histochemistry) was shown to have a wide but heterogeneous distribution in the central nervous system (CNS) at both regional and cellular levels. The highest labelling was observed in hippocampus (pyramidal and polymorph neurons) and olfactory bulb. Present data suggest that polyamine metabolism in the CNS is not homogeneous but rather that the preferential production of a polyamine species is region- and cell type-specific.

Acetyltransferases↗
PubMed1996

On the role of glucocorticoid receptors in brain plasticity.

1. The mapping of glucocorticoid receptors (GR) in the rat central nervous system (CNS) has demonstrated their widespread presence in large numbers of nerve and glial cell populations also outside the classical stress regions. 2. The present paper summarizes the evidence that glucocorticoids via GR in the CNS can act as lifelong organizing signals from development to aging. The following examples are given. (a) In the prepubertal and adult offspring, prenatal corticosterone treatment can produce long-lasting changes in striatal dopaminergic communication. (b) In adulthood, the evidence suggests complex regulation by adrenocortical hormones of neurotrophic factors and their receptors in the hippocampal formation. (c) In aging, the strongly GR-immunoreactive pyramidal cell layer of the CA1 hippocampal area appears to be preferentially vulnerable to neurotoxic actions of glucocorticoids, especially in some rat strains. 3. Strong evidence suggests that each nerve cell in the CNS is supported by a trophic unit, consisting of other nerve cells and glial cells, blood vessels, and extracellular matrix molecules. Due to multiple actions on nerve and glial cell populations of the different trophic units, the glucocorticoids may exert either an overall trophic or a neurotoxic action. It seems likely that with increasing age, the endangering actions of glucocorticoids on nerve cells prevail over the neurotrophic ones, leading to reduced nerve cell survival in some trophic units.

Adrenal Cortex Hormones↗
PubMed1996

Regulation of dopamine D2 receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCKB and D2L receptor cDNAs.

Alteration in dopamine (DA) and/or cholecystokinin (CCK) transmission in the CNS may be of relevance for schizophrenia. Previous findings in striatal membranes give indications of a modulation of DA D2 receptor affinity by CCKB receptor activation. In the present study receptor binding studies were performed in a mouse fibroblast cell line (L-hD2l/CCK), expressing both human D2 receptors (long form, D2L) and human CCKB receptors, and binding sites for [3H]CCK-8S (sulfated CCK octapeptide), the D2 agonist [3H]NPA and the D2 antagonist [3H]raclopride were found and characterized in saturation and competition experiments. 1 nM of CCK-8 caused a significant 38% increase in the KD value of the D2 agonist [3H]NPA binding sites in the L-hD2l/CCK cell membranes. This change was blocked by the CCKB receptor antagonist PD 134308 (50 nM). Furthermore, 1 nM of CCK-8 increased the KD value of the D2 antagonist [3H]raclopride binding sites by 34% (P < 0.05) in the L-hD2l/CCK cell membranes. Control cells (L-hD2l cells) expressing D2L receptors showed no specific [3H]CCK-8S binding sites and no modulation by CCK-8 of the D2L receptors. These findings indicate a modulation of the D2L receptor affinity by activation of the CCKB receptor also when they are coexpressed in a fibroblast cell line. One possible explanation of these data may include a receptor-receptor interaction between the CCKB and D2L receptors.

Animals↗
PubMed1996

Spermidine/spermine N1-acetyltransferase mRNA levels show marked and region-specific changes in the early phase after transient forebrain ischemia.

Considerable evidence points to an involvement of natural polyamines (putrescine, spermidine and spermine) in trophic regulation of brain tissue. Spermidine/spermine N1-acetyltransferase is the key enzyme in the interconversion pathway which leads to the formation of spermidine and putrescine from spermine and spermidine, respectively. In the present paper we have studied using in situ hybridization histochemistry the levels of spermidine/spermine N1-acetyltransferase mRNA in the rat central nervous system after transient forebrain ischemia. In the first hours after the insult, a modest increase in spermidine/spermine N1-acetyltransferase mRNA levels was observed in ependymal cells and other non-neuronal cells of all telencephalic and diencephalic regions. In addition, major increases in spermidine/spermine N1-acetyltransferase mRNA levels were observed in regions selectively vulnerable to the ischemic insult, such as striatum, hippocampus and cerebral cortex, during the first day post-reperfusion. The time course and extent of labelling increase were subregion- and cell-specific. At the cellular level, the labelling appeared markedly increased in neurons (8-10 fold in ventromedial striatum and CA1 region) and, to a lesser extent, in non-neuronal cells. The increase in SSAT mRNA levels was not directly related to cell degeneration, as it was detected in both some vulnerable and some resistant cell populations. However, the peak increase of SSAT labelling was precocious in resistant neurons (such as those of ventromedial striatum and dentate gyrus granular layer) and delayed or very limited in vulnerable neurons (such as those of CA1 pyramidal layer and dorsolateral striatum). The increase in spermidine/spermine N1-acetyltransferase may contribute to the increase in putrescine and decrease in spermidine levels observed after ischemia and gives further support to the notion that polyamine metabolism in the early phase after lesion is oriented towards putrescine production. This phenomenon could be relevant in determining the prevalence of neurotrophic vs. neurotoxic effects of polyamines.

Acetyltransferases↗