Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis

A potent stimulatory effect of Angiotensin-converting-enzyme inhibitors (ACEI) on cerebralarteriogenesis, involving bradykinin, was recently demonstrated by Hillmeister et. al, in a ratmodel of three-vessel occlusion. The evidences presented by the authors show clearly that thecollateral growth in the posterior cerebral artery occurs, resulting in blood supply and cerebralautoregulation recovery.Fil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentin

Renin-angiotensin sistem modulating funtions in the cpu.

The caudate-putamen (CPu) of the striatum is one of the main entrances to the basal ganglia. The CPu is fundamentally a dopaminergic area receiving dopamine innervation from the substantia nigra, ventral tegmental area, and mesencephalic structures, but also has noradrenergic inputs from a post-encephalic area, the locus coeruleus, and glutamatergic innervation from cortical structures and cholinergic and GABAergic interneurons. It is well known that functional interactions between different neurotransmission systems play a crucial integrative role in the caudate-putamen, and are widely recognized as contributing to central motor activity and movements, and also to the processing of cognitive and limbic functions, despite autonomic responses across the noradrenergic system. Not only does typical neurotransmission regulate these functions, but peptidergic systems also have an important role. The brain renin-angiotensin system (RAS) is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning and memory, and the regulation of emotional and behavioral responses. There is increasing ontogenetic, anatomic and functional evidence of the existence of a brain renin-angiotensin system and of its interaction with other putative neurotransmitters and their receptors. All components of the RAS have been observed in the striatum, and Ang II modulates dopamine release from striatal dopaminergic terminals, in vivo and in vitro, via their AT1 receptors. There is considerable evidence supporting a key role for dopamine (DA) neurotransmission in the Cpu in long-term neuroadaptative changes induced by stress or psychostimulants, such as cocaine or amphetamine. Repeated amphetamine or cocaine administration results in progressive and enduring enhancement of their psychomotor and positive reinforcing effects (sensitization phenomenon). We recently found evidence of the participation of Ang II, through its AT1 receptors, in the development of the locomotor sensitization induced by psychostimulant drugs. Moreover, the brain RAS may play a role in the pathogenesis and progression of Parkinson?s disease and aging-related loss of DA neurons. Manipulation of RAS components may be useful for neuroprotection in Parkinson?s disease patients because local RAS plays a major role in proinflammatory and pro-oxidative changes in aged substantia nigra. RAS is involved in modulating neurotransmission systems in the CPu and their functions, and for this reason it could be a possible target in the treatment of stress related diseases, drug abuse or neurodegenerative disorders.http://www.novapublishers.com/catalog/product_info.Fil: Bregonzio, Claudia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología, ArgentinaFil: Bregonzio, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba, Argentina.Fil: Marinzalda, M. A. Universidad Católica de Córdoba. Facultad de Ciencias Químicas. Laboratorio de Neurofarmacología, Argentina.Fil: Baiardi, Gustavo.Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, ArgentinaFil: Baiardi, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas, Argentina.Fil: Baiardi, Gustavo. Universidad Católica de Córdoba. Facultad de Ciencias Químicas. Laboratorio de Neurofarmacologia, Argentina.Fil: Paz, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba, Argentina , Argentina.Fil: Paz, María Constanza. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología, ArgentinaNeurociencias (incluye Psicofiosiología

AT1 Receptor as a Potential Target in Amphetamine-induced Neuro-inflammation

Background: Amphetamines constitute a group of drugs associated with clinical use and illicit consumption. They induce dopamine neurotransmission and promote astrocyte reactivity and microglial activation events associated with their neurotoxic actions. The neuroinflammatory response induced by amphetamines occurs as a consequence of mechanisms that involve oxidative stress, glial reactivity and apoptosis. Brain angiotensin II, through its AT1 receptor (AT1-R), modulates dopaminergic, glutamatergic and GABAergic neurotransmission, which are involve in cognition, emotions and stress responses. AT1-R is present in neurons, astrocytes, microglia and endothelial cells having a key role in the development of an oxidative/inflammatory microenvironment. AT1-R promotes the initiation and progression of local brain inflammatory and oxidative responses under dopamine imbalance conditions. The available evidences support the protective effects of AT1-R blockade for the deleterious effects induced by amphetamine.Conclusion: The available evidences, together with the results obtained by our group, open the possibility to postulate AT1-R as a possible therapeutic target for neuroinflammatory responses associated with dopamine imbalanced related disorders.Fil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Baiardi, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin

Brain angiotensin II in dopaminergic imbalance-derived pathologies: Neuroinflammation and vascular responses

Brain angiotensin II (ANG II) as a pleiotropic player: Mental disorders have been commonly associated with an imbalance in many neurotransmitter systems, such as dopamine, glutamate, and gamma-aminobutyric acid. Considering the complexity of brain functioning, all components of the neurovascular unit should be considered in studies for a better comprehension of the physiopathology and possible therapeutics. ANG II is present in the brain and binds to AT1 receptors (AT1-R), located in the neurovascular unit and has a close relationship with the mentioned neurotransmitter systems. In pathological conditions, AT1-R expressed in astrocytes, microglia, and brain endothelial cells are key mediators in the development of an oxidative/inflammatory microenvironment, as well as in glial activation. Therefore, pharmacological intervention targeting AT1-R provides a holistic and moderated approach to modulate neurotransmission systems in addition to the glial and vascular responses [Figure 1]. This interaction is underscored by several studies that related brain ANG II to neurological disorders, such as Parkinson´s disease (PD) and attention deficit hyperactivity disorder (ADHD).Fil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin

From brain to kidney: Central AT1 receptors and sympathetic nervous system interaction in sodium excretion mechanisms

Central angiotensin II through AT1 receptors (AT1-R), closely interact with sympathetic nervous system (SNS) in the maintenance of renal sodium equilibrium under normal and pathological conditions. Our aim was to unmask the brain AT1-R role in the renal sodium excretion mechanisms and the interaction with the SNS. For these purposes, male Wistar rats with renal nervous ablation/sham and implanted with bilateral cannulae in lateral ventricle, received normosodic (0.4 %) or hypersonic (4 %) diet in metabolic cages for 5 days. The surgical procedures were performed under ketamine/xylaxine (75/5 mg/kg i.p.) anesthesia. The urine was daily collected and water intake was register along the experiment. On day 6 the animals received saline/losartan (AT1- R antagonist 4ug/1 μl) intracerebrally and sacrificed 12 hours later. The parameters analyzed were; in urine: volume, sodium, potassium, water, creatinine and osmolarity to evaluate kidney function; at brain: c-Fos expression in paraventricular (PVN), supraoptic (SON) and subfornical (SFO) nucleus and vasopressin by immunohistochemistry. The data were analyzed by factorial ANOVA. The effects of central AT1-R and the interaction with SNS were observed on water intake and sodium and water excretion. Renal sodium excretion and water intake are under central AT1-R activation depending on renal nervous integrity. AT1-R blockade blunted the increased c-Fos expression induced by hypersodic diet in vasopressinergic neurons (PVN and SON). We conclude that SNS regulates the complex interaction between central angiotensin II, through AT1-R, and vasopressinergic neurons at SON and PVN under sodium overload conditions.Fil: Ruberto, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de Nanomedicina

Amphetamine induced differential effects in vascular and glial components at somatosensory cortex: Why to focus on AT1 receptors

Amphetamine (Amph), is associated with inflammatory processes, involving glial and vascular alterations. Brain Angiotensin II, through AT1-receptors (AT1-R), modulates dopaminergic neurotransmission and plays a crucial role in inflammatory responses. Our aim was to evaluate the role of AT1-R in long-term alterations induced by repeated exposure to Amph. Astrocyte and microglia reactivity, and brain microvascular network were analysed at the somatosensory cortex (S1 Barrel and S1 Trunk area). Male Wistar rats (250–320 g) were administered with AT1-R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1–10) and Amph/saline (2.5 mg/kg i.p., days 6–10). The four experimental groups at the two times evaluated (17 and 31 days) were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On days 17 and 31 the animals were sacrificed and their brains were processed for immunohistochemistry against GFAP (astroglial marker), CD11b (microglial marker) and von Willebrand factor (vascular marker). Data were analysed with factorial ANOVA followed by Bonferroni test. Our results indicate that Amph exposure induces an endurable increase in astrocyte and microglia reactivity at S1 Barrel and S1 Trunk area. Although, the microvascular rearrangement (evaluated as vascular area density, branching points and tortuosity) showed time dependant differential response to Amph, since at day 31 these parameters return to basal conditions at S1 Barrel. Meanwhile, at S1 Trunk the vascular changes were observed only at day 31. Pretreatment with the AT1-R blocker prevented the described alterations induced by Amph. We conclude that neuroplastic changes induced by Amph demand an AT1-R active role showing a regional susceptibility at vascular level.Fil: Armonelli Fiedler, Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaReunión anual de sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de Laboratori

Progesterone prevents impairment of cognitive, affective and motor events in a reserpine model of parkinsonism in male rats

Parkinson’s is a common neurodegenerative disorder, second only to Alzheimer´s disease.It has been the object of growing interest since its frequency tends to augment as life expectancyhas increased globally considered. In this work, we study the eventual neuroprotective effect ofProgesterone (P4) injected a few days before establishing a Reserpine (R) model of Parkinsonism inadult male rats. We focused on cognitive (Novel Object Recognition test; NOR), affective (ForcedSwimming Task; FST) and motor (Catalepsy Test; CT) outputs. We performed the appropriate testsalong with the administration for two weeks of low doses of R. Our results show very clearly thatP4 prevents the impairment of several tasks regarding the deleterious effects of R, without affectingnegatively other areas of the subject behavior. In total accordance with current information, weshow here that P4 -in particular- and neuroactive steroids -in general- are promising molecules todelay diverse manifestations of neurotransmitters depletion.Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Villegas, Vanina Anabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Mulle Bernedo, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; ArgentinaFil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; Argentin

Progesterone prevents impairment of cognitive, affective and motor events in a reserpine model of parkinsonism in male rats

Parkinson’s is a common neurodegenerative disorder, second only to Alzheimer´s disease.It has been the object of growing interest since its frequency tends to augment as life expectancyhas increased globally considered. In this work, we study the eventual neuroprotective effect ofProgesterone (P4) injected a few days before establishing a Reserpine (R) model of Parkinsonism inadult male rats. We focused on cognitive (Novel Object Recognition test; NOR), affective (ForcedSwimming Task; FST) and motor (Catalepsy Test; CT) outputs. We performed the appropriate testsalong with the administration for two weeks of low doses of R. Our results show very clearly thatP4 prevents the impairment of several tasks regarding the deleterious effects of R, without affectingnegatively other areas of the subject behavior. In total accordance with current information, weshow here that P4 -in particular- and neuroactive steroids -in general- are promising molecules todelay diverse manifestations of neurotransmitters depletion.Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Villegas, Vanina Anabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Mulle Bernedo, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; ArgentinaFil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; Argentin

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via Angiotensin Type 1 receptor: evidence from brain regional sensitivity to amphetamine

Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC) as well as cognitive alterations. Brain angiotensin II, through Angiotensin Type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, Candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterwards, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using Factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although, the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.Fil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Casarsa, Brenda Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Baiardi, Gustavo Carlos. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin

Amphetamine Induces Oxidative Stress, Glial Activation and Transient Angiogenesis in Prefrontal Cortex via AT1-R

Background: Amphetamine (AMPH) alters neurons, glia and microvessels, which affects neurovascular unit coupling, leading to disruption in brain functions such as attention and working memory. Oxidative stress plays a crucial role in these alterations. The angiotensin type I receptors (AT1-R) mediate deleterious effects, such as oxidative/inflammatory responses, endothelial dysfunction, neuronal oxidative damage, alterations that overlap with those observed from AMPH exposure. Aims: The aim of this study was to evaluate the AT1-R role in AMPH-induced oxidative stress and glial and vascular alterations in the prefrontal cortex (PFC). Furthermore, we aimed to evaluate the involvement of AT1-R in the AMPH-induced short-term memory and working memory deficit. Methods: Male Wistar rats were repeatedly administered with the AT1-R blocker candesartan (CAND) and AMPH. Acute oxidative stress in the PFC was evaluated immediately after the last AMPH administration by determining lipid and protein peroxidation. After 21 off-drug days, long-lasting alterations in the glia, microvessel architecture and to cognitive tasks were evaluated by GFAP, CD11b and von Willebrand immunostaining and by short-term and working memory assessment. Results: AMPH induced acute oxidative stress, long-lasting glial reactivity in the PFC and a working memory deficit that were prevented by AT1-R blockade pretreatment. Moreover, AMPH induces transient angiogenesis in PFC via AT1-R. AMPH did not affect short-term memory. Conclusion: Our results support the protective role of AT1-R blockade in AMPH-induced oxidative stress, transient angiogenesis and long-lasting glial activation, preserving working memory performance.Fil: Basmadjian, Osvaldo Martin. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Silvero, María Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Becerra, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentin